Azithromycin for Acute Exacerbations Requiring Hospitalization

NCT ID: NCT02135354

Last Updated: 2018-09-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 301 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-01
• Study Completion Date: 2018-04-30

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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

• 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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

• 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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Azitromcyine CF; ATC code: J01FA10; Inactive substance

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agentschap voor Innovatie door Wetenschap en Technologie

OTHER

Sponsor Role: collaborator

Wim Janssens

OTHER

Sponsor Role: lead

Responsible Party

Wim Janssens

MD. PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Wim Janssens, MD. PhD

Role: PRINCIPAL_INVESTIGATOR

KU Leuven - UZ Leuven

Locations

UZ Brussel

Brussels, Brussel Hoofdstedelijk Gewest, Belgium

St. Pieterziekenhuis

Brussels, Brussels Capital, Belgium

ZNA Middelheim

Antwerp, Flanders, Belgium

St. Augustinus Ziekenhuis

Antwerp, Flanders, Belgium

Imelda Ziekenhuis

Bonheiden, Flanders, Belgium

St. Jan Brugge Ziekenhuis

Bruges, Flanders, Belgium

Maria Middelaresziekenhuis

Ghent, Flanders, Belgium

UZ Gent

Ghent, Flanders, Belgium

Jessa Ziekenhuis

Hasselt, Flanders, Belgium

AZ Groeninge Ziekenhuis

Kortrijk, Flanders, Belgium

UZ Gasthuisberg

Leuven, Flanders, Belgium

Heilig Hart Ziekenhuis

Roeselare, Flanders, Belgium

St. Andriesziekenhuis

Tielt, Flanders, Belgium

CHU Charleroi

Charleroi, Wallonia, Belgium

Grand Hôpital de Charleroi

Gilly, Wallonia, Belgium

CHU Liège

Liège, Wallonia, Belgium

CHU Mont-Godinne

Yvoir, Wallonia, Belgium

Onze-Lieve-Vrouwziekenhuis

Aalst, , Belgium

Clinique Reine Astrid

Malmedy, , Belgium

Clinique Sainte-Elisabeth

Namur, , Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 31665017 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27099485 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.dovepress.com/the-belgian-trial-with-azithromycin-for-acute-copd-exacerbations-requi-peer-reviewed-article-COPD

Protocol paper

Other Identifiers

2013-004420-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IWT-TBM 130233

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

s55829 - BACE trial

Identifier Type: -

Identifier Source: org_study_id