Clinical trial NCT00415350: Bronchiectasis and Long Term Azithromycin Treatment
Official title: Bronchiectasis and Long Term Azithromycin Treatment: A Randomised Placebo-controlled Trial Studying Disease Modifying Effects of Immunomodulating Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bronchiectasis
Inflammation
Keywords: Bronchiectasis
Macrolide
Azithromycin
Antibiotic prophylaxis
Immunomodulation
Inflammation
Lung function
Sputum
Bacterial colonization
Lead sponsor: Medical Center Alkmaar
Sponsor class: OTHER
First posted: 2006-12-22
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Does prolonged antibiotic treatment with AZM reduce the number of bacterial exacerbations in patients with bronchiectasis?
timeFrame: 1 year
measure: Does treatment with AZM increase lung function parameters (Δ FEV1, Δ FVC )?
timeFrame: 1 year
Secondary outcomes:
measure: Is there any improvement in symptom score during treatment with AZM?
timeFrame: 1 year
measure: What is the effect of AZM on bacterial colonisation?
timeFrame: 1 year
measure: Does treatment with AZM reduce inflammatory parameters?
timeFrame: 1 year
measure: Does treatment with AZM change the quality of life?
timeFrame: 1 year
measure: Is there any differences in adverse events between AZM and placebo treatment?
timeFrame: 1 year
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Alkmaar Medical Center
state: N-H
city: Amsterdam
country: Netherlands
facility: AMC
city: Amsterdam
country: Netherlands
facility: St Lucas Andreas Ziekenhuis
city: Beverwijk
country: Netherlands
facility: Rode Kruis Ziekenhuis
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Groesbeek
country: Netherlands
facility: U.L.C. Dekkerswald
city: Groningen
country: Netherlands
facility: University Hospital Groningen (UMCG)
city: Heerlen
country: Netherlands
facility: Atrium Medisch Centrum
city: Hilversum
country: Netherlands
facility: Tergooi Ziekenhuizen
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis
city: Leeuwarden
country: Netherlands
facility: MC Leeuwarden
city: Nieuwegein
country: Netherlands
facility: Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
city: Venlo
country: Netherlands
facility: Viecuri MC
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: Medical Center Alkmaar, dep. Pulmomary Diseases
name: W.G. Boersma, MD,PHD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.