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Effects of Long Term Antibiotic Therapy on Exacerbation Rate in Stable COPD Patients

Primary Purpose

Chronic Obstructive Pulmonary Disease (COPD)

Status
Completed
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Doxycycline
Placebo
Sponsored by
Imperial College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease (COPD)

Eligibility Criteria

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

Inclusion Criteria:

  • Informed consent given
  • Confirmed COPD diagnosis
  • Severity of disease: Patients with a measured FEV1<80% of predicted normal values.
  • At least one treated exacerbation (Patient recalls an episode of symptomatic worsening which was treated and was consistent with a COPD exacerbation) in the previous year.
  • Age: ≥ 45 years of age at screening.
  • Able to complete questionnaires for health status and symptoms and considered able to comply with the dosing regimen.
  • Patients willing to report exacerbations and attend for study visits.

Exclusion Criteria:

  • Patients with a known diagnosis of active TB or other chronic respiratory disease in the judgement of the study doctor.
  • Hepatic or renal impairment as defined as LFTs > 5XULN, and eGFR<30 ml/min/1.73m2.
  • Patients with known hypersensitivity to Tetracyclines, the IMP and/or Placebo including their excipients.
  • Patients taking ongoing antibiotic therapy for COPD or other conditions.
  • Patients with uncontrolled clinically significant hypertension
  • Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding.
  • Patients with uncontrolled clinically relevant bradycardia, cardiac arrhythmias or cardiac insufficiency.
  • Clinically relevant abnormal electrolyes (sodium or potassium), renal function (urea and creatinine) or liver function (ALT, AST, ALP) that could interfere with the objectives of the trial or safety of the volunteer.
  • Patient taking clinically significant contraindicated medication, as per the SmPC for Doxycycline.
  • Use of another experimental investigational medicinal product within 3 months of study enrolment. If the IMP used was as part of the NIHR WP2 study then entry to WP3 after a 6 week washout period is permissible.
  • Patients with any other condition precluding enrolment in the trial, according to the assessment of the study doctor. This will be documented at screening

Sites / Locations

  • Aintree University Hospital NHS Foundation Trust
  • St Georges University Hospitals NHS Foundation Trust
  • Royal Brompton and Harefield Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Doxycycline

Placebo

Arm Description

Doxycycline: oral dose of 100 mg once daily, for a total duration of 52 weeks.

Placebo: an oral dose of one capsule once daily, for a total duration of 52 weeks.

Outcomes

Primary Outcome Measures

Rate of exacerbations (per person/year) recorded from date of drug issue until date of end of treatment visit.

Secondary Outcome Measures

Lung function (spirometry) (FEV1, FVC, FEV1/FVC ratio, FEV1 as % Predicted).
Total and individual component (symptoms, activity, impact) SGRQ scores will be used to measure health status.
Respiratory health status across groups as measured from total number of symptoms in a day and prevalence of individual symptoms recorded on daily diary cards.
Airway bacteria numbers taken from a sputum sample, provided by a subset of patients, at months 3, 6, 9, 12 after drug issue.
Changes in C-reactive protein (CRP) levels from baseline.
Hospital admissions. This data will be collected from Hospital Episode Statistics (HES).
Time to 1st exacerbation measured by diary cards in both therapy and placebo groups.
Rate of exacerbations treated with steroids and antibiotics.
Adherence as measured using pill counts.
Antibiotic resistance measured in the subset of patients (able to produce sputum) from sputum based on standard NHS procedures (not resistant, intermediate, severe, resistant).

Full Information

First Posted
November 20, 2014
Last Updated
July 24, 2017
Sponsor
Imperial College London
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1. Study Identification

Unique Protocol Identification Number
NCT02305940
Brief Title
Effects of Long Term Antibiotic Therapy on Exacerbation Rate in Stable COPD Patients
Official Title
A Phase III Double-blind, Randomised, Placebo Controlled Trial of Long Term Therapy on Exacerbation Rate in Patients With Stable COPD Using Doxycycline
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
July 12, 2017 (Actual)
Study Completion Date
July 12, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study investigates if long term use of the antibiotic doxycycline can reduce exacerbations in COPD patients. Half of the patients will receive doxycycline which the other half will receive a placebo.
Detailed Description
Chronic Obstructive Pulmonary Disease (COPD) is a common disease which can place a considerable burden on people who suffer from it. COPD exacerbations (periods when symptoms flare up) are a major cause of hospital admission in the UK. Bacterial infections play an important role in the development of COPD and so one possible treatment for COPD is with antibiotics. However, there is little information available about the use of long term antibiotics in the treatment of this disease. Therefore, the purpose of this study is to investigate if long term use of the antibiotic Doxycycline can reduce exacerbations and improve the outlook for these patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease (COPD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
222 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Doxycycline
Arm Type
Active Comparator
Arm Description
Doxycycline: oral dose of 100 mg once daily, for a total duration of 52 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo: an oral dose of one capsule once daily, for a total duration of 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Doxycycline
Intervention Description
An oral dose of 100 mg of Doxycycline once daily, for a total duration of 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
An oral dose of one capsule of placebo once daily, for a total duration of 52 weeks
Primary Outcome Measure Information:
Title
Rate of exacerbations (per person/year) recorded from date of drug issue until date of end of treatment visit.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Lung function (spirometry) (FEV1, FVC, FEV1/FVC ratio, FEV1 as % Predicted).
Time Frame
12 months of treatment
Title
Total and individual component (symptoms, activity, impact) SGRQ scores will be used to measure health status.
Time Frame
12 months of treatment
Title
Respiratory health status across groups as measured from total number of symptoms in a day and prevalence of individual symptoms recorded on daily diary cards.
Time Frame
12 months of treatment
Title
Airway bacteria numbers taken from a sputum sample, provided by a subset of patients, at months 3, 6, 9, 12 after drug issue.
Time Frame
12 months of treatment
Title
Changes in C-reactive protein (CRP) levels from baseline.
Time Frame
12 months of treatment
Title
Hospital admissions. This data will be collected from Hospital Episode Statistics (HES).
Time Frame
12 months of treatment
Title
Time to 1st exacerbation measured by diary cards in both therapy and placebo groups.
Time Frame
12 months of treatment
Title
Rate of exacerbations treated with steroids and antibiotics.
Time Frame
12 months of treatment
Title
Adherence as measured using pill counts.
Time Frame
12 months of treatment
Title
Antibiotic resistance measured in the subset of patients (able to produce sputum) from sputum based on standard NHS procedures (not resistant, intermediate, severe, resistant).
Time Frame
12 months of treatment
Other Pre-specified Outcome Measures:
Title
Pre-specified Exploratory Subgroup Analysis
Description
As co-morbidities for COPD are heterogeneous, exploratory analysis will be carried out to investigate whether there is an interaction with treatment- i.e. to investigate whether outcomes of treatment are either influenced by and/or restricted to patients with particular known co morbidities. The following will be looked at in this study: Cardiovascular disease. This included patients receiving treatment for Ischemic Heart Disease, hypertension and heart failure. Diabetes and/or known impaired glucose intolerance Body Mass Index (BMI)
Time Frame
12 months of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Informed consent given Confirmed COPD diagnosis Severity of disease: Patients with a measured FEV1<80% of predicted normal values. At least one treated exacerbation (Patient recalls an episode of symptomatic worsening which was treated and was consistent with a COPD exacerbation) in the previous year. Age: ≥ 45 years of age at screening. Able to complete questionnaires for health status and symptoms and considered able to comply with the dosing regimen. Patients willing to report exacerbations and attend for study visits. Exclusion Criteria: Patients with a known diagnosis of active TB or other chronic respiratory disease in the judgement of the study doctor. Hepatic or renal impairment as defined as LFTs > 5XULN, and eGFR<30 ml/min/1.73m2. Patients with known hypersensitivity to Tetracyclines, the IMP and/or Placebo including their excipients. Patients taking ongoing antibiotic therapy for COPD or other conditions. Patients with uncontrolled clinically significant hypertension Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding. Patients with uncontrolled clinically relevant bradycardia, cardiac arrhythmias or cardiac insufficiency. Clinically relevant abnormal electrolyes (sodium or potassium), renal function (urea and creatinine) or liver function (ALT, AST, ALP) that could interfere with the objectives of the trial or safety of the volunteer. Patient taking clinically significant contraindicated medication, as per the SmPC for Doxycycline. Use of another experimental investigational medicinal product within 3 months of study enrolment. If the IMP used was as part of the NIHR WP2 study then entry to WP3 after a 6 week washout period is permissible. Patients with any other condition precluding enrolment in the trial, according to the assessment of the study doctor. This will be documented at screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wisia Wedzicha, MD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aintree University Hospital NHS Foundation Trust
City
Liverpool
ZIP/Postal Code
L9 7AL
Country
United Kingdom
Facility Name
St Georges University Hospitals NHS Foundation Trust
City
London
ZIP/Postal Code
SW17 0RE
Country
United Kingdom
Facility Name
Royal Brompton and Harefield Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
SW36NP
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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Effects of Long Term Antibiotic Therapy on Exacerbation Rate in Stable COPD Patients

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