Azithromycin for Acute Exacerbations Requiring Hospitalization (BACE)

Wim Janssens

Status and phase: Terminated; Phase 3

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: Placebo; Drug: Azithromycin

Study type: Interventional

Funder types: Other

Identifiers

NCT02135354

s55829 - BACE trial

2013-004420-11 (EudraCT Number)

IWT-TBM 130233 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 301 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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301 participants in 2 patient groups, including a placebo group

Azithromycin

Experimental group

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

Treatment:

Drug: Azithromycin

Placebo

Placebo Comparator group

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

Treatment:

Drug: Placebo