Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation (AZI002)

This study has been completed.
Sponsor:
Collaborator:
Fund for Scientific Research, Flanders, Belgium
Information provided by (Responsible Party):
GM. Verleden, Katholieke Universiteit Leuven
ClinicalTrials.gov Identifier:
NCT01109160
First received: April 21, 2010
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation
Drug: Azithromycin Dihydrate
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation

Resource links provided by NLM:


Further study details as provided by Katholieke Universiteit Leuven:

Primary Outcome Measures:
  • Histology on bronchial and/or transbronchial biopsies [ Time Frame: after 3 months of treatment ] [ Designated as safety issue: No ]
    Evolution of lymphocytic airway inflammation after 3 months of treatment

  • Pulmonary function (FEV1) [ Time Frame: after 3 months of treatment ] [ Designated as safety issue: Yes ]
    Evolution of FEV1 after 3 months of treatment

  • Bronchoalveolar cellularity and protein levels (IL-8, IL-17) [ Time Frame: after 3 months of treatment ] [ Designated as safety issue: No ]
    Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment

  • Radiologic features [ Time Frame: after 3 months of treatment ] [ Designated as safety issue: No ]
    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:
  • Pulmonary function (FEV1) [ Time Frame: after 6 months of treatment ] [ Designated as safety issue: No ]
    Evolution of FEV1 after 6 months of treatment


Enrollment: 15
Study Start Date: April 2010
Study Completion Date: July 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azithromycin
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).
Drug: Azithromycin Dihydrate

Add-on of study-drug (azithromycin) to 'standard of care' at diagnosis of lymphocytic bronchi(oli)tis.

Study-drug regime: 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment).

Other Name: Azithromycin 250 mg, ZTM250, Zitromax TM (ATC J01FA10)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01109160

Locations
Belgium
University Hospital Gasthuisberg
Leuven, Vlaams-Brabant, Belgium, B-3000
Sponsors and Collaborators
Katholieke Universiteit Leuven
Fund for Scientific Research, Flanders, Belgium
Investigators
Principal Investigator: Geert M Verleden, MD, PhD KULeuven and UZ Leuven
  More Information

Publications:
Responsible Party: GM. Verleden, Medical Director Leuven Lung Transplant Programme, Katholieke Universiteit Leuven
ClinicalTrials.gov Identifier: NCT01109160     History of Changes
Other Study ID Numbers: AZI002, 2010-018724-16
Study First Received: April 21, 2010
Last Updated: July 3, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Katholieke Universiteit Leuven:
azithromycin
lymphocytic bronchitis or bronchiolitis
lung transplantation
acute allograft rejection
chronic allograft rejection
bronchiolitis obliterans syndrome

Additional relevant MeSH terms:
Bronchiolitis
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014