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Azithromycin for Acute Exacerbations Requiring Hospitalization (BACE)

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Terminated
Phase
Phase 3
Locations
Belgium
Study Type
Interventional
Intervention
Azithromycin
Placebo
Sponsored by
Wim Janssens
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring AECOPD, Chronic Obstructive Pulmonary Disease, Acute exacerbation, Hospitalization, Azithromycin, Macrolides, Randomized Controlled Trial, Placebo

Eligibility Criteria

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

Inclusion Criteria:

  • Established diagnosis of COPD by medical doctor (based on clinical history OR pulmonary function test)
  • Smoking history of at least 10 pack-years (10 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years, etc.)
  • Current hospitalization for potential infectious AECOPD treated with standard therapy
  • History of at least one exacerbation during the last year (prior to the current hospital admission) for which systemic steroids and/or antibiotics were taken
  • ECG at admission

Exclusion Criteria:

  • Mechanical or non-invasive ventilation at moment of randomization (D1)
  • Long QT interval on ECG (QTc > 450msec for males or > 470msec for females)
  • History of life-threatening arrhythmias
  • Myocardial infarction (NSTEMI or STEMI) less than 6 weeks before start of study drug
  • Unstable angina pectoris or acute myocardial infarction (NSTEMI or STEMI) at admission
  • Drugs with high risk for long QT interval and torsade de pointes (amiodarone, flecainide, procainamide, sotalol, droperidol, haldol, citalopram, other macrolides)
  • Documented uncorrected severe hypokalemia (K+ < 3.0 mmol/L) or hypomagnesemia (Mg2+ < 0.5 mmol/L)
  • Chronic systemic steroids (> 4 mg methylprednisolone /day for ≥ 2 months)
  • Actual use of macrolides for at least 2 weeks
  • Allergy to macrolides
  • Active cancer treatment
  • Life expectancy < 3 months
  • Pregnant or breast-feeding subjects. Woman of childbearing potential must have a pregnancy test performed and a negative result must be documented before start of treatment

Sites / Locations

  • UZ Brussel
  • St. Pieterziekenhuis
  • ZNA Middelheim
  • St. Augustinus Ziekenhuis
  • Imelda Ziekenhuis
  • St. Jan Brugge Ziekenhuis
  • Maria Middelaresziekenhuis
  • UZ Gent
  • Jessa Ziekenhuis
  • AZ Groeninge Ziekenhuis
  • UZ Gasthuisberg
  • Heilig Hart Ziekenhuis
  • St. Andriesziekenhuis
  • CHU Charleroi
  • Grand Hôpital de Charleroi
  • CHU Liège
  • CHU Mont-Godinne
  • Onze-Lieve-Vrouwziekenhuis
  • Clinique Reine Astrid
  • Clinique Sainte-Elisabeth

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Azithromycin

Placebo

Arm Description

N = 250 From day 1 up to and including day 3: 500 mg azithromycin PO once a day From day 4 up to and including day 90: 250 mg azithromycin PO once every 2 days

N = 250 From day 1 up to and including day 3: 500 mg placebo PO once a day From day 4 up to and including day 90: 250 mg placebo PO once every 2 days

Outcomes

Primary Outcome Measures

Time to clinical failure
Clinical failure is a composite endpoint as multiple clinical interventions may indicate that an initiated therapy is failing. Clinical failure is defined as the composite of death, treatment intensification (additional dose of systemic steroids, switch antibiotics for respiratory reasons or new course of systemic steroids and/or antibiotics) and step up in hospital care for respiratory reasons (from ward to ICU during index event, or from home to ward or ICU (new admission) after discharge). Primary outcome measure will also be analysed in following subgroups as an exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use

Secondary Outcome Measures

Number of clinical failures up to Day 90 (key secondary #1)
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III ICS use vs no ICS use
COPD Assessment Test (CAT) score at Day 90 (key secondary #2)
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Total days of additional/prolonged systemic steroid use at Day 90 (key secondary #3)
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Number of clinical failures up to Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III ICS use vs no ICS use
Time to clinical failure up to Day 90 and up to Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time to new exacerbation within 90 and within 270 days
A new exacerbation is defined as the composite of new course of systemic steroids and/or antibiotics, and hospitalization for respiratory reasons, all after the index event. Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Number of new exacerbations up to 90 days and up to 270 days
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Total days of hospital days within 90 and within 270 days
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Total days in intensive care within 90 and within 270 days
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Quality of Life - 5 Dimensions (EQ5D) score at Day 90 and at Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
COPD Assessment Test (CAT) score at Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Modified Medical Research Council (mMRC) score at Day 90 and Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Speech, Spatial and Qualities of Hearing (SSQ5) score at Day 90 and Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Pre-bronchodilator forced expiratory volume in 1 second (FEV1) at Day 90 and Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Total dose of additional/prolonged systemic steroids at Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Total days of additional/prolonged systemic steroid use at Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Total days of non-study antibiotic use at Day 90 and Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Number of home physician contacts at Day 90 and Day 270
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Average cost of hospitalization at Day 90 and Day 270 including the index hospitalization
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time to death within 90 and within 270 days
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time to first treatment intensification within 90 and within 270 days
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time to first step up in hospital care for respiratory reasons within 90 and within 270 days
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use

Full Information

First Posted
May 8, 2014
Last Updated
September 3, 2018
Sponsor
Wim Janssens
Collaborators
Agentschap voor Innovatie door Wetenschap en Technologie
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1. Study Identification

Unique Protocol Identification Number
NCT02135354
Brief Title
Azithromycin for Acute Exacerbations Requiring Hospitalization
Acronym
BACE
Official Title
Belgian Trial With Azithromycin During Acute COPD Exacerbations
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Terminated
Why Stopped
slow recruitment
Study Start Date
August 1, 2014 (Actual)
Primary Completion Date
October 2017 (Actual)
Study Completion Date
April 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Wim Janssens
Collaborators
Agentschap voor Innovatie door Wetenschap en Technologie

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This project (funded by the IWT-TBM program) will organize a randomized placebo-controlled multicenter intervention trial in 500 COPD patients to study the effectiveness and safety of azithromycin therapy in the acute setting of COPD exacerbations requiring hospital admission. Although long-term use of azithromycin is proven effective to prevent exacerbations, inherent risks outweigh the benefits. By reducing the dose and duration of the azithromycin treatment and by restricting the treatment to acute periods with highest risk for treatment failure, benefits may counterbalance potential side effects, which may result in a new treatment strategy for these acute events. The present study is designed by the services of respiratory medicine of the Leuven and Ghent University hospitals but will run in total in 17 different large hospitals in Belgium, of which 12 are located in Flanders.
Detailed Description
In this 9 month, randomized, placebo-controlled, parallel-group, multicenter intervention trial, 500 patients will be randomly assigned (1:1 ratio) to receive either azithromycin or placebo on top of standard therapy in the acute treatment of COPD exacerbations requiring hospitalization. The study drug (azithromycin or placebo) will be initiated and uploaded within 48 hours after hospital admission (500mg once a day for 3 days) and subsequently administered for a prolonged period of 3 months at a lower maintenance dose (250mg every 2 days). An additional follow-up period of 6 months without study drug will be foreseen to study relapse after study drug withdrawal.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
AECOPD, Chronic Obstructive Pulmonary Disease, Acute exacerbation, Hospitalization, Azithromycin, Macrolides, Randomized Controlled Trial, Placebo

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
The identity of the study drug will be concealed by the use of a format that is identical in packaging, labelling, schedule of administration and appearance. Patients will be randomly assigned in a 1:1 ratio to receive either azithromycin or placebo, with a permuted block size of ten and sequential assignment, stratified by the center. Randomization of the study drug is based on an online generated randomization schedule (http://www.randomization.com). Unique randomization codes are locally obtained through a secured Web-based program. At all times, randomization codes are kept strictly confidential during the study, with the exception of an ad hoc independent safety committee adjudicating cardiovascular side effects and mortality after 300 patients. Nevertheless, code breaks will be available at the site and un-blinding may occur in the case of an emergency which will require knowledge of the treatment assignment.
Allocation
Randomized
Enrollment
301 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Azithromycin
Arm Type
Experimental
Arm Description
N = 250 From day 1 up to and including day 3: 500 mg azithromycin PO once a day From day 4 up to and including day 90: 250 mg azithromycin PO once every 2 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
N = 250 From day 1 up to and including day 3: 500 mg placebo PO once a day From day 4 up to and including day 90: 250 mg placebo PO once every 2 days
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Other Intervention Name(s)
Azitromcyine CF, ATC code: J01FA10
Intervention Description
From day 1 up to and including day 3: 500 mg azithromycin PO once a day From day 4 up to and including day 90: 250 mg azithromycin PO once every 2 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Inactive substance
Intervention Description
From day 1 up to and including day 3: 500 mg placebo PO once a day From day 4 up to and including day 90: 250 mg placebo PO once every 2 days
Primary Outcome Measure Information:
Title
Time to clinical failure
Description
Clinical failure is a composite endpoint as multiple clinical interventions may indicate that an initiated therapy is failing. Clinical failure is defined as the composite of death, treatment intensification (additional dose of systemic steroids, switch antibiotics for respiratory reasons or new course of systemic steroids and/or antibiotics) and step up in hospital care for respiratory reasons (from ward to ICU during index event, or from home to ward or ICU (new admission) after discharge). Primary outcome measure will also be analysed in following subgroups as an exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed between day 1 (from 1 hour after first drug intake) till day 90 (24 hours after last study drug intake)
Secondary Outcome Measure Information:
Title
Number of clinical failures up to Day 90 (key secondary #1)
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase)
Title
COPD Assessment Test (CAT) score at Day 90 (key secondary #2)
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase)
Title
Total days of additional/prolonged systemic steroid use at Day 90 (key secondary #3)
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase)
Title
Number of clinical failures up to Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III ICS use vs no ICS use
Time Frame
Will be assessed on day 270 (last day of follow-up phase)
Title
Time to clinical failure up to Day 90 and up to Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Time to new exacerbation within 90 and within 270 days
Description
A new exacerbation is defined as the composite of new course of systemic steroids and/or antibiotics, and hospitalization for respiratory reasons, all after the index event. Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Number of new exacerbations up to 90 days and up to 270 days
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Total days of hospital days within 90 and within 270 days
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Total days in intensive care within 90 and within 270 days
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Quality of Life - 5 Dimensions (EQ5D) score at Day 90 and at Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
COPD Assessment Test (CAT) score at Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 270 (last day of follow-up phase)
Title
Modified Medical Research Council (mMRC) score at Day 90 and Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Speech, Spatial and Qualities of Hearing (SSQ5) score at Day 90 and Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Pre-bronchodilator forced expiratory volume in 1 second (FEV1) at Day 90 and Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Total dose of additional/prolonged systemic steroids at Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 270 (last day of follow-up phase)
Title
Total days of additional/prolonged systemic steroid use at Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 270 (last day of follow-up phase)
Title
Total days of non-study antibiotic use at Day 90 and Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Number of home physician contacts at Day 90 and Day 270
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Average cost of hospitalization at Day 90 and Day 270 including the index hospitalization
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Time to death within 90 and within 270 days
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Time to first treatment intensification within 90 and within 270 days
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Title
Time to first step up in hospital care for respiratory reasons within 90 and within 270 days
Description
Secondary outcome measure will also be analysed in following subgroups as exploratory analysis: Male vs female Smoker vs ex-smoker (stopped smoking > 6 months) GOLD A, B vs GOLD C vs GOLD D former GOLD I, II vs III vs IV High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL) Age > 65 years vs ≤ 65 years Anthonissen I vs Anthonissen II vs Anthonissen III at admission ICS use vs no ICS use
Time Frame
Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Established diagnosis of COPD by medical doctor (based on clinical history OR pulmonary function test) Smoking history of at least 10 pack-years (10 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years, etc.) Current hospitalization for potential infectious AECOPD treated with standard therapy History of at least one exacerbation during the last year (prior to the current hospital admission) for which systemic steroids and/or antibiotics were taken ECG at admission Exclusion Criteria: Mechanical or non-invasive ventilation at moment of randomization (D1) Long QT interval on ECG (QTc > 450msec for males or > 470msec for females) History of life-threatening arrhythmias Myocardial infarction (NSTEMI or STEMI) less than 6 weeks before start of study drug Unstable angina pectoris or acute myocardial infarction (NSTEMI or STEMI) at admission Drugs with high risk for long QT interval and torsade de pointes (amiodarone, flecainide, procainamide, sotalol, droperidol, haldol, citalopram, other macrolides) Documented uncorrected severe hypokalemia (K+ < 3.0 mmol/L) or hypomagnesemia (Mg2+ < 0.5 mmol/L) Chronic systemic steroids (> 4 mg methylprednisolone /day for ≥ 2 months) Actual use of macrolides for at least 2 weeks Allergy to macrolides Active cancer treatment Life expectancy < 3 months Pregnant or breast-feeding subjects. Woman of childbearing potential must have a pregnancy test performed and a negative result must be documented before start of treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wim Janssens, MD. PhD
Organizational Affiliation
KU Leuven - UZ Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Brussel
City
Brussel
State/Province
Brussel Hoofdstedelijk Gewest
ZIP/Postal Code
1090
Country
Belgium
Facility Name
St. Pieterziekenhuis
City
Brussel
State/Province
Brussels Hoofdstedelijk Gewest
ZIP/Postal Code
1000
Country
Belgium
Facility Name
ZNA Middelheim
City
Antwerpen
State/Province
Vlaanderen
ZIP/Postal Code
2020
Country
Belgium
Facility Name
St. Augustinus Ziekenhuis
City
Antwerpen
State/Province
Vlaanderen
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Imelda Ziekenhuis
City
Bonheiden
State/Province
Vlaanderen
ZIP/Postal Code
2820
Country
Belgium
Facility Name
St. Jan Brugge Ziekenhuis
City
Brugge
State/Province
Vlaanderen
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Maria Middelaresziekenhuis
City
Gent
State/Province
Vlaanderen
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Gent
City
Gent
State/Province
Vlaanderen
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Jessa Ziekenhuis
City
Hasselt
State/Province
Vlaanderen
ZIP/Postal Code
3500
Country
Belgium
Facility Name
AZ Groeninge Ziekenhuis
City
Kortrijk
State/Province
Vlaanderen
ZIP/Postal Code
8500
Country
Belgium
Facility Name
UZ Gasthuisberg
City
Leuven
State/Province
Vlaanderen
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Heilig Hart Ziekenhuis
City
Roeselare
State/Province
Vlaanderen
ZIP/Postal Code
8800
Country
Belgium
Facility Name
St. Andriesziekenhuis
City
Tielt
State/Province
Vlaanderen
ZIP/Postal Code
8700
Country
Belgium
Facility Name
CHU Charleroi
City
Charleroi
State/Province
Wallonië
ZIP/Postal Code
6110
Country
Belgium
Facility Name
Grand Hôpital de Charleroi
City
Gilly
State/Province
Wallonië
ZIP/Postal Code
6060
Country
Belgium
Facility Name
CHU Liège
City
Liège
State/Province
Wallonië
ZIP/Postal Code
4000
Country
Belgium
Facility Name
CHU Mont-Godinne
City
Yvoir
State/Province
Wallonië
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Onze-Lieve-Vrouwziekenhuis
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
Facility Name
Clinique Reine Astrid
City
Malmedy
ZIP/Postal Code
4960
Country
Belgium
Facility Name
Clinique Sainte-Elisabeth
City
Namur
ZIP/Postal Code
5000
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31665017
Citation
Vermeersch K, Belmans A, Bogaerts K, Gyselinck I, Cardinaels N, Gabrovska M, Aumann J, Demedts IK, Corhay JL, Marchand E, Slabbynck H, Haenebalcke C, Vermeersch S, Verleden GM, Troosters T, Ninane V, Brusselle GG, Janssens W; BACE trial investigators. Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo - a post-hoc analysis of the BACE randomized controlled trial. Respir Res. 2019 Oct 29;20(1):237. doi: 10.1186/s12931-019-1208-6.
Results Reference
derived
PubMed Identifier
27099485
Citation
Vermeersch K, Gabrovska M, Deslypere G, Demedts IK, Slabbynck H, Aumann J, Ninane V, Verleden GM, Troosters T, Bogaerts K, Brusselle GG, Janssens W. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial. Int J Chron Obstruct Pulmon Dis. 2016 Mar 31;11:687-96. doi: 10.2147/COPD.S95501. eCollection 2016.
Results Reference
derived
Links:
URL
https://www.dovepress.com/the-belgian-trial-with-azithromycin-for-acute-copd-exacerbations-requi-peer-reviewed-article-COPD
Description
Protocol paper

Learn more about this trial

Azithromycin for Acute Exacerbations Requiring Hospitalization

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