Back to resultsCorticosteroids in Community Acquired Pneumonia
Primary Purpose
Community-acquired Pneumonia, Cognition Disorder
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Prednisone
Placebo
Sponsored by
About this trial
This is an interventional other trial for Community-acquired Pneumonia
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 50 years
- Hospital admission to ward or ICU (including observation status admissions)
- Acute pneumonia defined as fulfilling each of the following two criteria: (a) New (<7-day duration) or worsening symptoms consistent with a lower respiratory tract infection, including ≥ 1 of the following: cough, shortness of breath, chest pain, sputum production, or decline in mental status; (b) Radiographic findings on chest x-ray or CT consistent with acute pulmonary infection, including pulmonary opacities, infiltrates, or pleural effusion.
- CRP ≥ 15 mg/dL within 24 hours of enrollment
Exclusion Criteria:
- Systemic steroid use within the past 30-days.
- Clinical team planning to treat with systemic steroids during this hospitalization independent of the study protocol.
- Unable to randomize patient within 24 hours of hospital presentation.
- Hospital-acquired pneumonia, defined as development of clinical and radiographic signs of pneumonia as an inpatient in an acute care hospital. (Residence in a nursing home or assisted living facility is not an exclusion criterion.)
- Unable to follow simple commands or non-verbal prior to this acute illness.
- Pre-existing severe dementia, defined as an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score ≥ 4.12.
- Concomitant acute decompensated heart failure requiring intravenous diuretics
- Serum sodium > 145 mEq/L (hypernatremia) or potassium < 3.5 mEq/L (hypokalemia) at screening and randomization
- Systolic blood pressure > 180 mmHg or a diastolic blood pressure > 100 mmHg at the start and end of screening.
- Any history of diabetes mellitus, having a serum blood glucose > 250 mg/dL, or requiring an anti-diabetic medication (e.g., insulin)
- Previous allergic or adverse reaction to a corticosteroid
- Severe immunosuppression, defined as any of the following: HIV with CD4 count < 200 cells/mm3, absolute neutrophil count < 500 cells/mm3, solid organ or hematopoietic stem cell transplant with in the past 90 days.
- Cystic fibrosis
- Active cancer, defined as new diagnosis or treatment for cancer in the past 6 months.
- Any history of adrenal insufficiency
- Substance abuse (alcohol, opioid, benzodiazepines, methamphetamines, cocaine) within the past year
- Any history of hospitalizations due to psychiatric illnesses within the past year
- Gastro-intestinal bleeding treated with hospital admission and/or blood transfusion within the past 3 months.
- Pre-existing medical condition resulting in a life expectancy < 6 months.
- Clinical team does not believe the patient should enter the study due to concerns about potential steroid-related complications.
- Alternative non-pneumonia illness accounts for the acute clinical or radiographic findings that meet the study's inclusion criteria.
- Unable to take the enteral study medicine by mouth or tube
- Prior enrollment in this study at any time
- Non-English speaking
- Confirmed or suspected COVID-19 as the cause of the patient's acute illness -
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Prednisone
Placebo
Arm Description
Patients randomized to the intervention arm will receive prednisone 50mg PO daily for 7 days.
Patients will receive matching placebo PO daily for 7 days.
Outcomes
Primary Outcome Measures
Feasibility as determined by the number of subjects who are successfully recruited and complete follow-up
Feasibility will be defined as: (a) recruitment and successful protocol completion of 100 patients; (b) corticosteroids being well tolerated, as shown by similar severity and frequency of adverse events in the intervention and placebo groups; (c) successful completion of 6-month cognitive assessments by >80% of survivors; and (d) the primary cognitive outcome Montreal Cognitive Assessment-Blind (MOCA-Blind) numerically favoring the intervention group with the one-tailed upper 80% confidence interval of the difference in MOCA-Blind between the intervention and placebo groups containing the minimally-important clinical difference (2 points on the MOCA-Blind).
Secondary Outcome Measures
Global cognition as measured by the Montreal Cognitive Assessment-Blind (MOCA-Blind)
This is a measure of global cognition based on the assessment of attention concentration, memory, language, conceptual thinking, calculations, and orientation. Scores range from 0 to 22 with higher scores indicating better cognition.
Severity of pneumonia symptoms as measured by the Community-Acquired Pneumonia Symptom (CAP-Sym) Questionnaire
This is a 18-item scale to determine the presence and severity of pneumonia symptoms. Each item is graded on a 6-point Likert scale. Scores range from 0 to 90 with higher scores indicating more severe symptoms.
Severity of pneumonia symptoms as measured by the Community-Acquired Pneumonia Symptom (CAP-Sym) Questionnaire
This is a 18-item scale to determine the presence and severity of pneumonia symptoms. Each item is graded on a 6-point Likert scale. Scores range from 0 to 90 with higher scores indicating more severe symptoms.
Severity of pneumonia symptoms as measured by the Community-Acquired Pneumonia Symptom (CAP-Sym) Questionnaire
This is a 18-item scale to determine the presence and severity of pneumonia symptoms. Each item is graded on a 6-point Likert scale. Scores range from 0 to 90 with higher scores indicating more severe symptoms.
Quality of life as measured by the EQ-5D-5L
Characterizes quality of life and contains 5-dimensions ("5D") related to everyday living: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It asks patients to rate their current global health status from 0 (worst health you can imagine) to 100 (best health you can imagine). Scores range from -0.573 to 1.000 with higher scores indicating better quality of life.
Basic activities of daily living (ADL) as measured by the Barthel's Index
Quantifies pre-illness basic ADLs such as bathing, dressing, toileting, transferring, continence, and feeding. Scores range from 0 to 20 with higher scores indicating better functioning.
Instrumental ADL as measured by Lawton Instrumental Activities of Daily Living Scale (IADLs)
Quantifies pre-illness IADLs - ability to use the phone, shopping, food preparation, housekeeping, laundry, transportation, medication management, and finances. Scores range from 0 to 8 with higher scores indicating better functioning.
Employment status as characterized by the Outcomes After Critical Illness and Surgery (OACIS) Employment Status Questionnaire
9-item survey that characterizes the patient's baseline (prior to the critical illness) and current level of employment (full, partial, or not employed). Patients will be categorized as loss of employment or no loss of employment.
Vital status (dead / alive)
Death during the index hospitalization will be recorded.
Vital status (dead / alive)
Death within 6-months will be recorded.
Intensive care unit admission (yes/no)
Intensive care unit admission at any point during the index hospitalization will be recorded.
Mechanical ventilation (yes/no)
Invasive mechanical ventilation is defined as new assisted positive pressure breathing through an endotracheal tube or tracheostomy for any duration. Noninvasive ventilation through a mask or nasal prongs does not satisfy the outcome of invasive mechanical ventilation.
Vasopressor use (yes/no)
defined as the administration of any of the following medications by continuous infusion for at least 1 hour during the index hospitalization: norepinephrine, epinephrine, dopamine, phenylephrine or vasopressin.
Pleural drainage (yes/no)
Pleural drainage is defined as removal of fluid from the pleural space by any procedure at the bedside or in the operating room during the index hospitalization; procedures such as thoracentesis and video-assisted thorascopic surgery (VATS) may be used to drain pleural fluid.
Hospital length of stay in (days)
Duration of hospitalization (presentation to hospital discharge) will be recorded.
Full Information
NCT ID
NCT04652414
First Posted
November 24, 2020
Last Updated
February 6, 2023
Sponsor
Vanderbilt University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04652414
Brief Title
Corticosteroids in Community Acquired Pneumonia
Official Title
Corticosteroid Treatment for Community-Acquired Pneumonia to Improve Long-term Cognition: A Pilot Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Limited enrollment due to the COVID-19 pandemic. Sponsor withdrew funding.
Study Start Date
December 1, 2020 (Actual)
Primary Completion Date
July 30, 2022 (Actual)
Study Completion Date
July 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single-center, blinded, placebo-controlled pilot RCT evaluating corticosteroids for the treatment of Community Acquired Pneumonia (CAP) that will enroll 100 adults hospitalized with community-acquired pneumonia. The primary goal is to assess the feasibility of proposed trial procedures for use in a subsequent phase III trial powered on 6-month cognitive outcome (MOCA-Blind score). Key outcomes are six-month cognitive and functional status, duration and severity of symptoms, and mortality.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Community-acquired Pneumonia, Cognition Disorder
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prednisone
Arm Type
Experimental
Arm Description
Patients randomized to the intervention arm will receive prednisone 50mg PO daily for 7 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive matching placebo PO daily for 7 days.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone 50mg will be administered enterally for 7 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
This is a matching placebo to prednisone.
Primary Outcome Measure Information:
Title
Feasibility as determined by the number of subjects who are successfully recruited and complete follow-up
Description
Feasibility will be defined as: (a) recruitment and successful protocol completion of 100 patients; (b) corticosteroids being well tolerated, as shown by similar severity and frequency of adverse events in the intervention and placebo groups; (c) successful completion of 6-month cognitive assessments by >80% of survivors; and (d) the primary cognitive outcome Montreal Cognitive Assessment-Blind (MOCA-Blind) numerically favoring the intervention group with the one-tailed upper 80% confidence interval of the difference in MOCA-Blind between the intervention and placebo groups containing the minimally-important clinical difference (2 points on the MOCA-Blind).
Time Frame
1.5 years
Secondary Outcome Measure Information:
Title
Global cognition as measured by the Montreal Cognitive Assessment-Blind (MOCA-Blind)
Description
This is a measure of global cognition based on the assessment of attention concentration, memory, language, conceptual thinking, calculations, and orientation. Scores range from 0 to 22 with higher scores indicating better cognition.
Time Frame
6-months
Title
Severity of pneumonia symptoms as measured by the Community-Acquired Pneumonia Symptom (CAP-Sym) Questionnaire
Description
This is a 18-item scale to determine the presence and severity of pneumonia symptoms. Each item is graded on a 6-point Likert scale. Scores range from 0 to 90 with higher scores indicating more severe symptoms.
Time Frame
3-days
Title
Severity of pneumonia symptoms as measured by the Community-Acquired Pneumonia Symptom (CAP-Sym) Questionnaire
Description
This is a 18-item scale to determine the presence and severity of pneumonia symptoms. Each item is graded on a 6-point Likert scale. Scores range from 0 to 90 with higher scores indicating more severe symptoms.
Time Frame
7-days
Title
Severity of pneumonia symptoms as measured by the Community-Acquired Pneumonia Symptom (CAP-Sym) Questionnaire
Description
This is a 18-item scale to determine the presence and severity of pneumonia symptoms. Each item is graded on a 6-point Likert scale. Scores range from 0 to 90 with higher scores indicating more severe symptoms.
Time Frame
30-days
Title
Quality of life as measured by the EQ-5D-5L
Description
Characterizes quality of life and contains 5-dimensions ("5D") related to everyday living: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It asks patients to rate their current global health status from 0 (worst health you can imagine) to 100 (best health you can imagine). Scores range from -0.573 to 1.000 with higher scores indicating better quality of life.
Time Frame
6-months
Title
Basic activities of daily living (ADL) as measured by the Barthel's Index
Description
Quantifies pre-illness basic ADLs such as bathing, dressing, toileting, transferring, continence, and feeding. Scores range from 0 to 20 with higher scores indicating better functioning.
Time Frame
6-months
Title
Instrumental ADL as measured by Lawton Instrumental Activities of Daily Living Scale (IADLs)
Description
Quantifies pre-illness IADLs - ability to use the phone, shopping, food preparation, housekeeping, laundry, transportation, medication management, and finances. Scores range from 0 to 8 with higher scores indicating better functioning.
Time Frame
6-months
Title
Employment status as characterized by the Outcomes After Critical Illness and Surgery (OACIS) Employment Status Questionnaire
Description
9-item survey that characterizes the patient's baseline (prior to the critical illness) and current level of employment (full, partial, or not employed). Patients will be categorized as loss of employment or no loss of employment.
Time Frame
6-months
Title
Vital status (dead / alive)
Description
Death during the index hospitalization will be recorded.
Time Frame
Baseline to hospital discharge, approximately 5 days
Title
Vital status (dead / alive)
Description
Death within 6-months will be recorded.
Time Frame
6-months
Title
Intensive care unit admission (yes/no)
Description
Intensive care unit admission at any point during the index hospitalization will be recorded.
Time Frame
Baseline to hospital discharge, approximately 5 days
Title
Mechanical ventilation (yes/no)
Description
Invasive mechanical ventilation is defined as new assisted positive pressure breathing through an endotracheal tube or tracheostomy for any duration. Noninvasive ventilation through a mask or nasal prongs does not satisfy the outcome of invasive mechanical ventilation.
Time Frame
Baseline to hospital discharge, approximately 5 days
Title
Vasopressor use (yes/no)
Description
defined as the administration of any of the following medications by continuous infusion for at least 1 hour during the index hospitalization: norepinephrine, epinephrine, dopamine, phenylephrine or vasopressin.
Time Frame
Baseline to hospital discharge, approximately 5 days
Title
Pleural drainage (yes/no)
Description
Pleural drainage is defined as removal of fluid from the pleural space by any procedure at the bedside or in the operating room during the index hospitalization; procedures such as thoracentesis and video-assisted thorascopic surgery (VATS) may be used to drain pleural fluid.
Time Frame
Baseline to hospital discharge, approximately 5 days
Title
Hospital length of stay in (days)
Description
Duration of hospitalization (presentation to hospital discharge) will be recorded.
Time Frame
Baseline to hospital discharge, approximately 5 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 50 years
Hospital admission to ward or ICU (including observation status admissions)
Acute pneumonia defined as fulfilling each of the following two criteria: (a) New (<7-day duration) or worsening symptoms consistent with a lower respiratory tract infection, including ≥ 1 of the following: cough, shortness of breath, chest pain, sputum production, or decline in mental status; (b) Radiographic findings on chest x-ray or CT consistent with acute pulmonary infection, including pulmonary opacities, infiltrates, or pleural effusion.
CRP ≥ 15 mg/dL within 24 hours of enrollment
Exclusion Criteria:
Systemic steroid use within the past 30-days.
Clinical team planning to treat with systemic steroids during this hospitalization independent of the study protocol.
Unable to randomize patient within 24 hours of hospital presentation.
Hospital-acquired pneumonia, defined as development of clinical and radiographic signs of pneumonia as an inpatient in an acute care hospital. (Residence in a nursing home or assisted living facility is not an exclusion criterion.)
Unable to follow simple commands or non-verbal prior to this acute illness.
Pre-existing severe dementia, defined as an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score ≥ 4.12.
Concomitant acute decompensated heart failure requiring intravenous diuretics
Serum sodium > 145 mEq/L (hypernatremia) or potassium < 3.5 mEq/L (hypokalemia) at screening and randomization
Systolic blood pressure > 180 mmHg or a diastolic blood pressure > 100 mmHg at the start and end of screening.
Any history of diabetes mellitus, having a serum blood glucose > 250 mg/dL, or requiring an anti-diabetic medication (e.g., insulin)
Previous allergic or adverse reaction to a corticosteroid
Severe immunosuppression, defined as any of the following: HIV with CD4 count < 200 cells/mm3, absolute neutrophil count < 500 cells/mm3, solid organ or hematopoietic stem cell transplant with in the past 90 days.
Cystic fibrosis
Active cancer, defined as new diagnosis or treatment for cancer in the past 6 months.
Any history of adrenal insufficiency
Substance abuse (alcohol, opioid, benzodiazepines, methamphetamines, cocaine) within the past year
Any history of hospitalizations due to psychiatric illnesses within the past year
Gastro-intestinal bleeding treated with hospital admission and/or blood transfusion within the past 3 months.
Pre-existing medical condition resulting in a life expectancy < 6 months.
Clinical team does not believe the patient should enter the study due to concerns about potential steroid-related complications.
Alternative non-pneumonia illness accounts for the acute clinical or radiographic findings that meet the study's inclusion criteria.
Unable to take the enteral study medicine by mouth or tube
Prior enrollment in this study at any time
Non-English speaking
Confirmed or suspected COVID-19 as the cause of the patient's acute illness -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Han, MD,MSc
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wesley Self, MD, MPH
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Corticosteroids in Community Acquired Pneumonia
We'll reach out to this number within 24 hrs