Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation - Full Text View

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:	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:

MedlinePlus related topics: Lung Transplantation

Drug Information available for: Azithromycin Azithromycin dihydrate Azithromycin monohydrate

U.S. FDA Resources

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
Bronchoalveolar cellularity and protein levels [ Time Frame: after 6 months of treatment ] [ Designated as safety issue: No ]
Evolution of bronchoalveolar cellularity and protein levels after 6 months of treatment
Radiologic features [ Time Frame: after 6 months of treatment ] [ Designated as safety issue: No ]
Evolution of radiologic features on chest X-ray or HRCT after 6 months of treatment
Pulmonary function (FEV1) [ Time Frame: after 1 year of treatment ] [ Designated as safety issue: No ]
Evolution of FEV1 after 1 year of treatment
Bronchoalveolar cellularity and protein levels [ Time Frame: after 1 year of treatment ] [ Designated as safety issue: No ]
Evolution of bronchoalveolar cellularity and protein levels after 1 year of treatment
Radiologic features [ Time Frame: after 1 year of treatment ] [ Designated as safety issue: Yes ]
Evolution of radiologic features on chest X-ray or HRCT after 1 year of treatment.
Prevalence of chronic rejection (diagnosed as bronchiolitis obliterans syndrome, BOS) [ Time Frame: after 1 year of treatment ] [ Designated as safety issue: No ]
Prevalence of chronic rejection (diagnosed as BOS) after 1 year of treatment
Prevalence of chronic rejection (diagnosed as bronchiolitis obliterans syndrome or BOS) [ Time Frame: 2 years after initiation of treatment ] [ Designated as safety issue: No ]
Prevalence of chronic rejection (diagnosed as BOS) 2 years after initiation of treatment
Overall survival [ Time Frame: after 1 year of treatment ] [ Designated as safety issue: No ]
Overall survival after 1 year of treatment
Overall survival [ Time Frame: 2 years after initiation of treatment ] [ Designated as safety issue: No ]
Overall survival 2 years after initiation of treatment

Estimated Enrollment:	20
Study Start Date:	April 2010
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	April 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 (1 year 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 (1 year 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

Contacts

Contact: Geert M Verleden, MD, PhD	+32 16 34 68 08 ext Prof. Dr.	geert.verleden@uzleuven.be
Contact: Bart M Vanaudenaerde, PhD	+32 16 33 01 95 ext Dr.	bart.vanaudenaerde@med.kuleuven.be

Locations

Belgium
University Hospital Gasthuisberg	Recruiting
Leuven, Vlaams-Brabant, Belgium, B-3000
Contact: Geert M Verleden, Md, PhD +32 16 34 68 08 ext Prof. Dr. geert.verleden@uzleuven.be
Contact: Bart M Vanaudenaerde, PhD +32 16 33 01 95 ext Dr. bart.vanaudenaerde@med.kuleuven.be
Principal Investigator: Geert M Verleden, MD, PhD
Sub-Investigator: Bart M Vanaudenaerde, PhD
Sub-Investigator: Robin Vos, MD
Sub-Investigator: Lieven J Dupont, MD, PhD

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:

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.

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.

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.

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.

Responsible Party:	Prof. Dr. GM. Verleden, KULeuven and University Hospitals Leuven
ClinicalTrials.gov Identifier:	NCT01109160 History of Changes
Other Study ID Numbers:	AZI002, 2010-018724-16
Study First Received:	April 21, 2010
Last Updated:	April 22, 2010
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 May 23, 2013

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