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Azithromycin for Acute Exacerbations Requiring Hospitalization (BACE)

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ClinicalTrials.gov Identifier: NCT02135354
Recruitment Status : Terminated (slow recruitment)
First Posted : May 9, 2014
Last Update Posted : September 5, 2018
Sponsor:
Collaborator:
Agentschap voor Innovatie door Wetenschap en Technologie
Information provided by (Responsible Party):
Wim Janssens, KU Leuven

Tracking Information
First Submitted Date  ICMJE May 8, 2014
First Posted Date  ICMJE May 9, 2014
Last Update Posted Date September 5, 2018
Actual Study Start Date  ICMJE August 1, 2014
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2017)
Time to clinical failure [ 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) ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: May 8, 2014)
Time to treatment failure [ 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) ]
Clinical failure is a composite endpoint as multiple clinical interventions may indicate that an initiated therapy is failing. Clinical failure is defined as either death or the referral to intensive care for respiratory reasons, the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new exacerbation after discharge. Primary outcome measure will also be analysed in following subgroups:
  • 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 < 60 years vs age 60 - 70 years vs age > 70 years
  • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
  • ICS use vs no ICS use
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2017)
  • Number of clinical failures up to Day 90 (key secondary #1) [ Time Frame: Will be assessed on day 90 (last day of treatment phase) ]
    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) [ Time Frame: Will be assessed on day 90 (last day of treatment phase) ]
    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) [ Time Frame: Will be assessed on day 90 (last day of treatment phase) ]
    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 [ Time Frame: Will be assessed on day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2014)
  • Number of treatment failures [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III
    • ICS use vs no ICS use
  • Time to new exacerbation [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Number of new exacerbations [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Rate of exacerbations [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Days of hospitalisation [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Days of intensive care [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Symptom and quality of life scores [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Pre- and post-bronchodilator FEV1 [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Total dose of systemic steroids [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Total days of antibiotic use [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Number of home physician contacts [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
  • Average cost of hospitalization [ Time Frame: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase) ]
    Secondary outcome measure will also be analysed in following subgroups:
    • 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 < 60 years vs age 60 - 70 years vs age > 70 years
    • Anthonissen I vs Anthonissen II vs Anthonissen III at admission
    • ICS use vs no ICS use
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Azithromycin for Acute Exacerbations Requiring Hospitalization
Official Title  ICMJE Belgian Trial With Azithromycin During Acute COPD Exacerbations
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
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.
Primary Purpose: Treatment
Condition  ICMJE Chronic Obstructive Pulmonary Disease
Intervention  ICMJE
  • Drug: Azithromycin
    • 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
    Other Names:
    • Azitromcyine CF
    • ATC code: J01FA10
  • Drug: Placebo
    • 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
    Other Name: Inactive substance
Study Arms  ICMJE
  • Experimental: Azithromycin

    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
    Intervention: Drug: Azithromycin
  • Placebo Comparator: Placebo

    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: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 11, 2017)
301
Original Estimated Enrollment  ICMJE
 (submitted: May 8, 2014)
500
Actual Study Completion Date  ICMJE April 2018
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02135354
Other Study ID Numbers  ICMJE s55829 - BACE trial
2013-004420-11 ( EudraCT Number )
IWT-TBM 130233 ( Other Grant/Funding Number: Agentschap voor Innovatie door Wetenschap en Technologie )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Wim Janssens, KU Leuven
Study Sponsor  ICMJE Wim Janssens
Collaborators  ICMJE Agentschap voor Innovatie door Wetenschap en Technologie
Investigators  ICMJE
Principal Investigator: Wim Janssens, MD. PhD KU Leuven - UZ Leuven
PRS Account KU Leuven
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP