Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation

Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation Clinical Trial

— AZI002  

Official title:

A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01109160
• Other study ID #: AZI002
• Secondary ID: 2010-018724-16
• Status: Completed
• Phase: Phase 4
• First received: April 21, 2010
• Last updated: July 3, 2013
• Start date: April 2010
• Est. completion date: July 2013

Study information

• Verified date: July 2013
• Source: Katholieke Universiteit Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchitis
• Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation

Intervention

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).

Locations

Country	Name	City	State
Belgium	University Hospital Gasthuisberg	Leuven	Vlaams-Brabant

Sponsors (2)

Lead Sponsor	Collaborator
Katholieke Universiteit Leuven	Fund for Scientific Research, Flanders, Belgium

Country where clinical trial is conducted

Belgium, 

References & Publications (4)

Vanaudenaerde BM, De Vleeschauwer SI, Vos R, Meyts I, Bullens DM, Reynders V, Wuyts WA, Van Raemdonck DE, Dupont LJ, Verleden GM. The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2008 Sep;8(9):1911-20. doi: 10.1111/j.1600-6143.2008.02321.x. — View Citation

Vanaudenaerde BM, Dupont LJ, Wuyts WA, Verbeken EK, Meyts I, Bullens DM, Dilissen E, Luyts L, Van Raemdonck DE, Verleden GM. The role of interleukin-17 during acute rejection after lung transplantation. Eur Respir J. 2006 Apr;27(4):779-87. — View Citation

Vanaudenaerde BM, Wuyts WA, Geudens N, Dupont LJ, Schoofs K, Smeets S, Van Raemdonck DE, Verleden GM. Macrolides inhibit IL17-induced IL8 and 8-isoprostane release from human airway smooth muscle cells. Am J Transplant. 2007 Jan;7(1):76-82. Epub 2006 Oct 25. — View Citation

Verleden GM, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE. Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2006 Sep 1;174(5):566-70. Epub 2006 Jun 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histology on bronchial and/or transbronchial biopsies	Evolution of lymphocytic airway inflammation after 3 months of treatment	after 3 months of treatment	No
Primary	Pulmonary function (FEV1)	Evolution of FEV1 after 3 months of treatment	after 3 months of treatment	Yes
Primary	Bronchoalveolar cellularity and protein levels (IL-8, IL-17)	Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment	after 3 months of treatment	No
Primary	Radiologic features	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	after 3 months of treatment	No
Secondary	Pulmonary function (FEV1)	Evolution of FEV1 after 6 months of treatment	after 6 months of treatment	No