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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Lung Diseases
Lung Diseases, Obstructive
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on October 29, 2014