Bronchiectasis and Long Term Azithromycin Treatment (BAT)

Bronchiectasis and Long Term Azithromycin Treatment: A Randomised Placebo-controlled Trial Studying Disease Modifying Effects of Immunomodulating Treatment

1. SUMMARY

Rationale: Patients with bronchiectasis often experience lower respiratory tract infections with progression of symptoms and decline in quality of life. Macrolides, as has been shown in panbronchiolitis and cystic fibrosis, may break or weaken the link between infection and inflammation resulting in an improvement of symptoms. Also the number of exacerbations may lowered.

Objective: A reduction in number of infective exacerbations and improvement in lung function by AZT treatment are the primary objectives. Secondary objectives that will be evaluated are: symptoms score, quality of life, inflammatory parameters, bacterial colonisation, and adverse events.

Study design: Randomised double blind multicenter study in the Netherlands. Patients will be stratified for colonisation with P.aeruginosa.

Study population: Patients with bronchiectasis demonstrated by high-resolution computed tomography (HR-CT) scan or bronchography.

Intervention: Patients receive Azithromycin 250mg(p.o.) once daily or placebo.

Main study parameters/endpoints: Reduction in number exacerbations, defined as increase symptoms such as dyspnoea, coughing, and sputum production for which a course of prednisolone and/or antibiotic is needed. Change in lung function parameters (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC]) measured by spirometry is the other primary endpoint.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk of participating in this study is low. Laboratory, radiographic examinations, and pulmonary function tests are commonly used as diagnostic procedures during outpatients visits and during exacerbations. Adverse effects in maintenance treatment with AZT are usually mild and mainly gastrointestinal. Sometimes rash and abnormal liver function tests are observed. A better quality of life will probably be the beneficial effect of long term treatment with AZT. This will be achieved by a reduction in respiratory and non-respiratory symptoms and number of exacerbations.

Study Overview

• Status: Completed
• Conditions: Inflammation; Bronchiectasis
• Intervention / Treatment: Drug: Azithromycin; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • AMC
  • Amsterdam, Netherlands
    • st Lucas Andreas Ziekenhuis
  • Beverwijk, Netherlands
    • Rode Kruis Ziekenhuis
  • Deventer, Netherlands
    • Deventer Ziekenhuis
  • Groesbeek, Netherlands
    • U.L.C. Dekkerswald
  • Groningen, Netherlands
    • University Hospital Groningen (UMCG)
  • Heerlen, Netherlands
    • Atrium medisch centrum
  • Hilversum, Netherlands
    • Tergooi ziekenhuizen
  • Hoofddorp, Netherlands
    • Spaarne Ziekenhuis
  • Leeuwarden, Netherlands
    • MC Leeuwarden
  • Nieuwegein, Netherlands
    • Antonius Ziekenhuis
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Utrecht, Netherlands
    • Diakonessenhuis
  • Venlo, Netherlands
    • VieCuri MC
  • Zwolle, Netherlands
    • ISALA Klinieken
  • N-H
    • Alkmaar, N-H, Netherlands, 1800AM
      • Alkmaar Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18 ≥ years
• Bronchiectasis diagnosed by plain bronchography or high resolution computer tomography.
• Minimal 3 lower respiratory tract infections (LRTI) treated with oral/intravenous (IV) antibiotics in the year preceding the study inclusion.
• The presence of chronic respiratory symptoms such as cough, dyspnoea, expectoration of sputum.
• At least one positive sputum culture in the preceding year.
• Informed consent

Exclusion Criteria:

• Previous ( ≥ 4 weeks) prolonged macrolide therapy.
• Pregnant or lactating women.
• Allergy to macrolides.
• Intolerance to macrolides.
• Liver disease (alanine transaminase and/or aspartate transaminase levels 2 or more times the upper limit of normal).
• Use of antibiotics within 14 days of screening.
• Use of oral or IV corticosteroids (≥ 30 mg prednisolone/daily) within 30 days of screening.
• Other research medication started 2 months prior to inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo 2	Other: Placebo; Placebo tablet 1 daily
Active Comparator: Azithromycin treatment 1	Drug: Azithromycin; Azithromycin Tablet 250 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Does prolonged antibiotic treatment with AZM reduce the number of bacterial exacerbations in patients with bronchiectasis?	1 year
Does treatment with AZM increase lung function parameters (Δ FEV1, Δ FVC )?	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Is there any improvement in symptom score during treatment with AZM?	1 year
What is the effect of AZM on bacterial colonisation?	1 year
Does treatment with AZM reduce inflammatory parameters?	1 year
Does treatment with AZM change the quality of life?	1 year
Is there any differences in adverse events between AZM and placebo treatment?	1 year

Collaborators and Investigators

• Sponsor: W.G.Boersma
• Investigators: Study Director: W.G. Boersma, MD,PHD, Medical Center Alkmaar, dep. Pulmomary Diseases

Publications and helpful links

General Publications

• Terpstra LC, Altenburg J, Mohamed Hoesein FA, Bronsveld I, Go S, van Rijn PAC, De Jong PA, Heijerman HGM, Boersma WG. The effect of maintenance azithromycin on radiological features in patients with bronchiectasis - Analysis from the BAT randomized controlled trial. Respir Med. 2022 Feb;192:106718. doi: 10.1016/j.rmed.2021.106718. Epub 2021 Dec 28.
• Altenburg J, de Graaff CS, Stienstra Y, Sloos JH, van Haren EH, Koppers RJ, van der Werf TS, Boersma WG. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA. 2013 Mar 27;309(12):1251-9. doi: 10.1001/jama.2013.1937.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: December 21, 2006
• First Submitted That Met QC Criteria: December 21, 2006
• First Posted (Estimate): December 22, 2006

Study Record Updates

• Last Update Posted (Actual): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 26, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Inflammation; Azithromycin; Lung function; Bronchiectasis; Immunomodulation; Antibiotic prophylaxis; Macrolide; Sputum; Bacterial colonization
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; Inflammation; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: BAT-2006-MCA1; BAT-2006