Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation

Phase 4

Completed

• Conditions: Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation
• Interventions: Drug: Azithromycin Dihydrate

• Registration Number: NCT01109160
• Lead Sponsor: KU Leuven

Brief Summary

This study investigates the role of azithromycin treatment for lymphocytic bronchitis/bronchiolitis after lung transplantation.

Detailed Description

Lymphocytic bronchitis/bronchiolitis is one of the major risk factors for development of chronic rejection/BOS after lung transplantation. There is currently no established treatment available for this condition. There is now mounting evidence that IL-17 producing lymphocytes (TH17) not only participate in chronic allograft rejection/BOS, but are also present within the airway wall during lymphocytic bronchiolitis and that IL-17 mRNA-levels in bronchoalveolar lavage fluid of these patients are upregulated. As such, TH17 may account for the increased BAL neutrophilia seen in these patients, as IL-17 may be responsible for driving IL-8 secretion (a neutrophil-attracting chemokine) from various cell types in the airways. Since azithromycin has previously been shown to reduce both IL-17 induced IL-8 production by human airway smooth muscle cells 'in vitro' and bronchoalveolar IL-8/neutrophil levels in LTx recipients with established BOS, we believe that azithromycin has great potential for treating lymphocytic bronchi(oli)tis by attenuating this TH17/IL-17/IL-8-mediated airway inflammation, possibly even halting the subsequent development of chronic rejection/BOS after lung transplantation. In this study, histologic, spirometric, bronchoalveolar an radiologic features will be investigated in patients treated with confirmed lymphocytic bronchitis/bronchiolitis treated with azithromycin.

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-04-21
• Study First Submitted QC: 2010-04-22
• Study First Posted: 2010-04-23
• Primary Completion: 2012-10
• Status Verified: 2013-07
• Study Completion: 2013-07
• Last Update Submitted: 2013-07-03
• Last Update Posted: 2013-07-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Signed informed consent
• Adult (age at least 18 years old at moment of transplantation)
• Able to take oral medication
• Histologic diagnosis of lymphocytic bronchiolitis or bronchitis ('grade B') without concurrent acute cellular allograft rejection 'grade A' ≥2

Exclusion Criteria

• Severe suture problems (e.g. airway stenosis) requiring lasering or stenting

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Azithromycin	Azithromycin Dihydrate	Add-on of study-drug (azithromycin) to 'standard of care': 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment).

Primary Outcome Measures

Name	Time	Method
Histology on bronchial and/or transbronchial biopsies	after 3 months of treatment	Evolution of lymphocytic airway inflammation after 3 months of treatment
Pulmonary function (FEV1)	after 3 months of treatment	Evolution of FEV1 after 3 months of treatment
Bronchoalveolar cellularity and protein levels (IL-8, IL-17)	after 3 months of treatment	Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment
Radiologic features	after 3 months of treatment	Evolution of radiologic features (e.g. tree-in-bud, consolidation, bronchiectasis, air trapping, etc.) on chest X-ray or HRCT after 3 months of treatment

Secondary Outcome Measures

Name	Time	Method
Pulmonary function (FEV1)	after 6 months of treatment	Evolution of FEV1 after 6 months of treatment

Trial Locations

Locations (1)

University Hospital Gasthuisberg; 🇧🇪 Leuven, Vlaams-Brabant, Belgium