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Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease (TREAT)

Primary Purpose

Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation

Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Roflumilast
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation focused on measuring COPD, Chronic obstructive pulmonary disease, Roflumilast

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Written informed consent (IC)
  • Age ≥ 40 years
  • History of COPD for at least 12 months prior to enrollment (Visit V0)
  • Chronic productive cough for 3 months in each of the 2 years prior to enrollment (if other causes of productive cough have been excluded) and/or an exacerbation with predominantly bronchitic symptoms at enrollment
  • Presentation of an acute exacerbation of COPD that will be associated with increased sputum volume or change in sputum colour
  • Documented fixed airway obstruction determined by an FEV1/FVC ratio (post-bronchodilator) < 70% (if a pulmonary function test is not possible at Visit V0 a previous measurement can be taken which must not be older than 6 months)
  • Former smoker (defined as: smoking cessation at least 1 year ago) or current smoker both with a smoking history of at least 10 pack years

Main Exclusion Criteria:

  • Diagnosis of asthma and/or other relevant lung disease
  • Known alpha-1-antitrypsin deficiency
  • Recurrent exacerbations (within 8 weeks of a preceding exacerbation)
  • Treatment of current exacerbation with oral corticosteroids and/or antibiotics already started at enrollment
  • Treatment with PDE4 inhibitors within 3 months prior to Visit V0
  • Other protocol-defined exclusion criteria may apply

Sites / Locations

  • Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Roflumilast

Placebo

Arm Description

added on to standard therapy for acute COPD exacerbations

added on to standard therapy for acute COPD exacerbations

Outcomes

Primary Outcome Measures

Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.

Secondary Outcome Measures

Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) and were determined with a Neubauer hemocytometer.
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) and were determined with a Neubauer hemocytometer.
Change From Baseline in Sputum Marker Total Cells (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Total Cells (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of neutrophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of neutrophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction. A negative change from Baseline indicates improvement.
Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of macrophages was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of macrophages was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of eosinophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of eosinophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of lymphocytes was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of lymphocytes was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-6 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-6 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-8 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-8 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker MPO was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker MPO was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker Neutrophil Elastase was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker Neutrophil Elastase was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
Blood was collected and serum biomarker IL-6 was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
Blood was collected and serum biomarker IL-6 was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
Blood was collected and serum biomarker IL-1β was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
Blood was collected and serum biomarker IL-1β was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
Blood was collected and serum biomarker CRP was measured using Roche Modular Analytics E 170 Module. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
Blood was collected and serum biomarker CRP was measured using Roche Modular Analytics E 170 Module. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
Biomarker Plasma fibrinogen was determined using the method described by Clauss. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
Biomarker Plasma fibrinogen was determined using the method described by Clauss. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker Glucose (Initial Approach)
Blood was collected and analyzed for serum glucose levels. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Blood Biomarker Glucose (Extended Approach)
Blood was collected and analyzed for serum glucose levels. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Change From Baseline in FEV1/FVC (Initial Approach)
FEV1/FVC is the percentage of the vital capacity which is expired in the first second of maximal expiration. In healthy patients the FEV1/FVC is usually around 70%. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Change From Baseline in FEV1/FVC (Extended Approach)
FEV1/FVC is the percentage of the vital capacity which is expired in the first second of maximal expiration. In healthy patients the FEV1/FVC is usually around 70%. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst).
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst).
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst). A negative change from Baseline indicates improvement. Covariates for MMRM are stable state value, treatment, time point, and treatment by time point interaction.
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst). A negative change from Baseline indicates improvement. Covariates for MMRM are stable state value, treatment, time point, and treatment by time point interaction.
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status.
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status.
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, time point, treatment by time point and baseline by time point interaction.
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, time point, treatment by time point and baseline by time point interaction.
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Morning post-medication PEF (the best of 3 attempts measured with a mini-Wright peak-flow meter) was recorded in a daily diary. A positive change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Morning post-medication PEF (the best of 3 attempts measured with a mini-Wright peak-flow meter) was recorded in a daily diary. A positive change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Any increase in the following respiratory symptoms: dyspnea, sputum purulence, sputum amount, wheeze, sore throat, cough, fever, symptoms of a common cold, ie, nasal congestion and discharge over the previous 24 hours were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Any increase in the following respiratory symptoms: dyspnea, sputum purulence, sputum amount, wheeze, sore throat, cough, fever, symptoms of a common cold, ie, nasal congestion and discharge over the previous 24 hours were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Any changes in the participant's usual treatment were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Any changes in the participant's usual treatment were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Estimates of the length of time the participants were out of their own home on the previous day were recorded in a daily diary. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Estimates of the length of time the participants were out of their own home on the previous day were recorded in a daily diary. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Exacerbation Length (Initial Approach)
Exacerbation length is the period from start of increased symptoms to end of increased symptoms; the last day of an exacerbation was to be followed by 2 days without symptom entries in the diary.
Exacerbation Length (Extended Approach)
Exacerbation length is the period from start of increased symptoms to end of increased symptoms; the last day of an exacerbation was to be followed by 2 days without symptom entries in the diary.
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach)
Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness. A negative change from Baseline indicates improvement. Covariates for MMRM are baseline value, treatment, visit, and treatment by visit interaction.
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach)
Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness. A negative change from Baseline indicates improvement. Covariates for MMRM are baseline value, treatment, visit, and treatment by visit interaction.

Full Information

First Posted
October 31, 2011
Last Updated
December 22, 2016
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT01473758
Brief Title
Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Acronym
TREAT
Official Title
Effect of Roflumilast 500 μg Tablets Once Daily at Acute COPD Exacerbations Treated With Standard Therapy of Oral Steroids and Antibiotics. A Randomised, Double-blind, Placebo-controlled, Parallel-group Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Terminated
Why Stopped
Company decision: No Safety or Efficacy Concerns
Study Start Date
February 2012 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this trial is to investigate if roflumilast can reduce the neutrophilic inflammation at acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD). In addition, the potential benefit of roflumilast on severity and recovery periods of acute COPD exacerbations will be assessed using patient diaries and questionnaires.
Detailed Description
Participants will be asked whether they agree to participate in the measurements of arterial stiffness. Participants who agree will be included in the substudy, with the target of 60 patients with arterial stiffness measurements to complete the trial. Study was terminated due to difficulty in identifying further eligible patients for this exploratory study within a reasonable time.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation
Keywords
COPD, Chronic obstructive pulmonary disease, Roflumilast

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Roflumilast
Arm Type
Active Comparator
Arm Description
added on to standard therapy for acute COPD exacerbations
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
added on to standard therapy for acute COPD exacerbations
Intervention Type
Drug
Intervention Name(s)
Roflumilast
Intervention Description
500 µg tablet, od, oral administration in the morning after breakfast
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
tablet, od, oral administration in the morning after breakfast
Primary Outcome Measure Information:
Title
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.
Time Frame
Baseline and Day 14
Title
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.
Time Frame
Baseline and Day 14
Secondary Outcome Measure Information:
Title
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) and were determined with a Neubauer hemocytometer.
Time Frame
Day 14
Title
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) and were determined with a Neubauer hemocytometer.
Time Frame
Day 14
Title
Change From Baseline in Sputum Marker Total Cells (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Total Cells (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of neutrophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of neutrophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction. A negative change from Baseline indicates improvement.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of macrophages was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of macrophages was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of eosinophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of eosinophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of lymphocytes was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of lymphocytes was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-6 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-6 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-8 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-8 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker MPO was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker MPO was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker Neutrophil Elastase was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
Description
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker Neutrophil Elastase was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
Description
Blood was collected and serum biomarker IL-6 was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
Description
Blood was collected and serum biomarker IL-6 was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
Description
Blood was collected and serum biomarker IL-1β was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
Description
Blood was collected and serum biomarker IL-1β was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
Description
Blood was collected and serum biomarker CRP was measured using Roche Modular Analytics E 170 Module. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
Description
Blood was collected and serum biomarker CRP was measured using Roche Modular Analytics E 170 Module. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
Description
Biomarker Plasma fibrinogen was determined using the method described by Clauss. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
Description
Biomarker Plasma fibrinogen was determined using the method described by Clauss. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker Glucose (Initial Approach)
Description
Blood was collected and analyzed for serum glucose levels. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Blood Biomarker Glucose (Extended Approach)
Description
Blood was collected and analyzed for serum glucose levels. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
Description
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
Description
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
Description
Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
Description
Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in FEV1/FVC (Initial Approach)
Description
FEV1/FVC is the percentage of the vital capacity which is expired in the first second of maximal expiration. In healthy patients the FEV1/FVC is usually around 70%. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Change From Baseline in FEV1/FVC (Extended Approach)
Description
FEV1/FVC is the percentage of the vital capacity which is expired in the first second of maximal expiration. In healthy patients the FEV1/FVC is usually around 70%. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Time Frame
Baseline and Day 7, Day 14, Day 28 and Day 56
Title
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Description
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst).
Time Frame
Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Description
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst).
Time Frame
Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Description
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst). A negative change from Baseline indicates improvement. Covariates for MMRM are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Description
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst). A negative change from Baseline indicates improvement. Covariates for MMRM are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Description
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status.
Time Frame
Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Description
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status.
Time Frame
Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Description
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, time point, treatment by time point and baseline by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Description
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, time point, treatment by time point and baseline by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Description
Morning post-medication PEF (the best of 3 attempts measured with a mini-Wright peak-flow meter) was recorded in a daily diary. A positive change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Description
Morning post-medication PEF (the best of 3 attempts measured with a mini-Wright peak-flow meter) was recorded in a daily diary. A positive change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Description
Any increase in the following respiratory symptoms: dyspnea, sputum purulence, sputum amount, wheeze, sore throat, cough, fever, symptoms of a common cold, ie, nasal congestion and discharge over the previous 24 hours were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Description
Any increase in the following respiratory symptoms: dyspnea, sputum purulence, sputum amount, wheeze, sore throat, cough, fever, symptoms of a common cold, ie, nasal congestion and discharge over the previous 24 hours were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Description
Any changes in the participant's usual treatment were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Description
Any changes in the participant's usual treatment were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Description
Estimates of the length of time the participants were out of their own home on the previous day were recorded in a daily diary. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Description
Estimates of the length of time the participants were out of their own home on the previous day were recorded in a daily diary. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Title
Exacerbation Length (Initial Approach)
Description
Exacerbation length is the period from start of increased symptoms to end of increased symptoms; the last day of an exacerbation was to be followed by 2 days without symptom entries in the diary.
Time Frame
8 Weeks
Title
Exacerbation Length (Extended Approach)
Description
Exacerbation length is the period from start of increased symptoms to end of increased symptoms; the last day of an exacerbation was to be followed by 2 days without symptom entries in the diary.
Time Frame
8 Weeks
Title
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach)
Description
Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness. A negative change from Baseline indicates improvement. Covariates for MMRM are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Days 14 and 28
Title
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach)
Description
Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness. A negative change from Baseline indicates improvement. Covariates for MMRM are baseline value, treatment, visit, and treatment by visit interaction.
Time Frame
Baseline and Days 14 and 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent (IC) Age ≥ 40 years History of COPD for at least 12 months prior to enrollment (Visit V0) Chronic productive cough for 3 months in each of the 2 years prior to enrollment (if other causes of productive cough have been excluded) and/or an exacerbation with predominantly bronchitic symptoms at enrollment Presentation of an acute exacerbation of COPD that will be associated with increased sputum volume or change in sputum colour Documented fixed airway obstruction determined by an FEV1/FVC ratio (post-bronchodilator) < 70% (if a pulmonary function test is not possible at Visit V0 a previous measurement can be taken which must not be older than 6 months) Former smoker (defined as: smoking cessation at least 1 year ago) or current smoker both with a smoking history of at least 10 pack years Main Exclusion Criteria: Diagnosis of asthma and/or other relevant lung disease Known alpha-1-antitrypsin deficiency Recurrent exacerbations (within 8 weeks of a preceding exacerbation) Treatment of current exacerbation with oral corticosteroids and/or antibiotics already started at enrollment Treatment with PDE4 inhibitors within 3 months prior to Visit V0 Other protocol-defined exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha
City
London
ZIP/Postal Code
NW3 2PF
Country
United Kingdom
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28146642
Citation
Mackay AJ, Patel ARC, Singh R, Sapsford RJ, Donaldson GC, Prasad N, Goehring UM, Nip TK, Wedzicha JA. Randomized Double-Blind Controlled Trial of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Sep 1;196(5):656-659. doi: 10.1164/rccm.201612-2518LE. No abstract available.
Results Reference
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Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease

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