Chronic Obstructive Pulmonary DiseasePhase 3BACENCT02135354
Azithromycin for Acute Exacerbations Requiring Hospitalization
A Phase 3 study testing Azithromycin in people with Chronic Obstructive Pulmonary Disease, run by Wim Janssens at 20 sites in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Azithromycin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 301 participants
- Where
- 20 sitesBelgium
- Study dates
- 1 Aug 2014to Apr 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 13Show fewer
- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Belgium20 sites
Onze-Lieve-Vrouwziekenhuis
Aalst, 9300
ZNA Middelheim
Antwerp, Flanders, 2020
St. Augustinus Ziekenhuis
Antwerp, Flanders, 2610
Imelda Ziekenhuis
Bonheiden, Flanders, 2820
St. Jan Brugge Ziekenhuis
Bruges, Flanders, 8000
UZ Brussel
Brussels, Brussel Hoofdstedelijk Gewest, 1090
St. Pieterziekenhuis
Brussels, Brussels Capital, 1000
CHU Charleroi
Charleroi, Wallonia, 6110
Maria Middelaresziekenhuis
Ghent, Flanders, 9000
UZ Gent
Ghent, Flanders, 9000
Grand Hôpital de Charleroi
Gilly, Wallonia, 6060
Jessa Ziekenhuis
Hasselt, Flanders, 3500
AZ Groeninge Ziekenhuis
Kortrijk, Flanders, 8500
UZ Gasthuisberg
Leuven, Flanders, 3000
CHU Liège
Liège, Wallonia, 4000
Clinique Reine Astrid
Malmedy, 4960
Clinique Sainte-Elisabeth
Namur, 5000
Heilig Hart Ziekenhuis
Roeselare, Flanders, 8800
St. Andriesziekenhuis
Tielt, Flanders, 8700
CHU Mont-Godinne
Yvoir, Wallonia, 5530
About this study
Official title: Belgian Trial With Azithromycin During Acute COPD Exacerbations
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.
Read the 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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Azithromycin, Placebo
- Keywords
- AECOPD, Chronic Obstructive Pulmonary Disease, Acute exacerbation, Hospitalization, Azithromycin, Macrolides, Randomized Controlled Trial, Placebo
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Also called Azitromcyine CF, ATC code: J01FA10
- 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
PlaceboDrug
Also called Inactive substance
- 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
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin | Experimental | 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 Receives: Drug: Azithromycin |
| Placebo | Placebo comparator | 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Will be assessed between day 1 (from 1 hour after first drug intake) till day 90 (24 hours after last study drug intake)
Secondary outcomes (22)
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
Measured: Will be assessed on day 90 (last day of treatment phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase)
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
Measured: Will be assessed on day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
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
Measured: Will be assessed on day 90 (last day of treatment phase) and day 270 (last day of follow-up phase)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2014 (estimated)
- Study start1 Aug 2014
- Primary completionOct 2017
- Study completionApr 2018
Why it stopped: slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 301 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wim Janssens
- Sponsor type
- University, hospital or other
- Collaborators
- Agentschap voor Innovatie door Wetenschap en Technologie
- Responsible party
- Sponsor-investigator, Wim Janssens, KU Leuven
- Investigators
- Wim Janssens, MD. PhD, Principal investigator, KU Leuven - UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02135354
- Sponsor's protocol ID
- s55829 - BACE trial
- Other IDs
- 2013-004420-11, IWT-TBM 130233
- Acronym
- BACE
- Status last verified
- Sep 2018
- First submitted
- 8 May 2014
- Last updated
- 5 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 31665017Vermeersch 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.
PubMed 27099485
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Belgian Trial With Azithromycin During Acute COPD Exacerbations
- ClinicalTrials.gov ID
- NCT02135354
- Acronym / sponsor ID
- BACE / s55829 - BACE trial
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- AECOPD, Chronic Obstructive Pulmonary Disease, Acute exacerbation, Hospitalization, Azithromycin, Macrolides, Randomized Controlled Trial, Placebo
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow recruitment
- Enrolment
- 301 participants (actual)
- Lead sponsor
- Wim JanssensUniversity, hospital or other
- Collaborators
- Agentschap voor Innovatie door Wetenschap en Technologie
- Study start
- 1 Aug 2014 (actual)
- Primary completion
- Oct 2017 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 9 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Experimental | Drug: AzithromycinN = 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 |
| Placebo | Placebo comparator | Drug: PlaceboN = 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzithromycinAlso: Azitromcyine CF, ATC code: J01FA10* 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 | Drug | Azithromycin |
| PlaceboAlso: Inactive substance* 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 | Drug | Placebo |
Primary outcome
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
22 secondary outcomes
Number of clinical failures up to Day 90 (key secondary #1)
Time frame: Will be assessed on day 90 (last day of treatment phase)
COPD Assessment Test (CAT) score at Day 90 (key secondary #2)
Time frame: Will be assessed on day 90 (last day of treatment phase)
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)
Number of clinical failures up to Day 270
Time frame: Will be assessed on day 270 (last day of follow-up phase)
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)
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)
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)
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)
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)
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)
COPD Assessment Test (CAT) score at Day 270
Time frame: Will be assessed on day 270 (last day of follow-up phase)
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)
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)
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)
Total dose of additional/prolonged systemic steroids at Day 270
Time frame: Will be assessed on day 270 (last day of follow-up phase)
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)
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)
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)
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)
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)
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)
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)
Results and safety
The study was stopped early (reason given: slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2018.
- Derived from this study: PubMed 31665017Vermeersch 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.
- Derived from this study: PubMed 27099485Vermeersch 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.
- Protocol paperLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wim Janssens, MD. PhD principal investigator
KU Leuven - UZ Leuven
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azithromycin in people with Chronic Obstructive Pulmonary Disease, run by Wim Janssens at 20 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: slow recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02135354, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2018.