Bronchiectasis and Long Term Azithromycin Treatment

NCT00415350 | Completed Phase 3

• 2 other identifiers: BAT-2006-MCA1BAT-2006
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Bronchiectasis; Inflammation

Keywords

Bronchiectasis; Macrolide; Azithromycin; Antibiotic prophylaxis; Immunomodulation; Inflammation; Lung function; Sputum; Bacterial colonization

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

Study Arms (2)

Azithromycin treatment 1

ACTIVE COMPARATOR

Drug: Azithromycin

Placebo 2

PLACEBO COMPARATOR

Other: Placebo

Interventions

Azithromycin DRUG

Azithromycin Tablet 250 mg daily

Azithromycin treatment 1

Placebo OTHER

Placebo tablet 1 daily

Placebo 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 ≥ years
• Bronchiectasis diagnosed by plain bronchography or high resolution computer tomography.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• W.G.Boersma: lead

Study Sites (16)

Alkmaar Medical Center

Alkmaar, N-H, 1800AM, Netherlands

Location

AMC

Amsterdam, Netherlands

Location

St Lucas Andreas Ziekenhuis

Amsterdam, Netherlands

Location

Rode Kruis Ziekenhuis

Beverwijk, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

U.L.C. Dekkerswald

Groesbeek, Netherlands

Location

University Hospital Groningen (UMCG)

Groningen, Netherlands

Location

Atrium Medisch Centrum

Heerlen, Netherlands

Location

Tergooi Ziekenhuizen

Hilversum, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, Netherlands

Location

MC Leeuwarden

Leeuwarden, Netherlands

Location

Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Diakonessenhuis

Utrecht, Netherlands

Location

Viecuri MC

Venlo, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 34974413 DERIVED

• 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.

  PMID: 23532241 DERIVED

MeSH Terms

Conditions

Bronchiectasis; Inflammation

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• W.G. Boersma, MD,PHD

  Medical Center Alkmaar, dep. Pulmomary Diseases

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Doctor, MD

Study Record Dates

• First Submitted: December 21, 2006
• First Posted: December 22, 2006
• Study Start: April 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2010
• Last Updated: May 28, 2020

Record last verified: 2020-05

Locations

NL (16)