Azithromycin in Bronchiolitis Obliterans Syndrome

Graft Rejection Clinical Trial

— AZI001  

Official title:

Randomized Double-blind Placebo-controlled Prevention Trial of Azithromycin in Lung Transplantation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01009619
• Other study ID #: AZI001
• Secondary ID: EudraCT ref. 200
• Status: Completed
• Phase: Phase 4
• First received: November 6, 2009
• Last updated: August 29, 2011
• Start date: September 2005
• Est. completion date: December 2009

Study information

• Verified date: August 2011
• Source: Katholieke Universiteit Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines AgencyBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
• Study type: Interventional

Clinical Trial Summary

Preventive treatment with azithromycin reduces the prevalence fo Bronchiolitis Obliterans Syndrome after lung transplantation.

Description:

• Prospective, interventional, randomized, double-blind, placebo-controlled trial.

• Clinical setting (tertiary University Hospital).

• Investigator-driven, no pharmaceutical sponsor.

• Lung transplant recipients.

• Add-on of study-drug (placebo or azithromycin) to 'standard of care' (standardized, routine immunosuppressive and infectious prophylactic protocol).

• 1:1 inclusion ratio (placebo:azithromycin).

• Randomisation at discharge after informed consent.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Stable LTx recipients at discharge after transplantation.

• Signed informed consent

• Adult (age at least 18 years old at moment of transplantation)

• Able to take oral medication

Exclusion Criteria:

• Prolonged and/or complicated ICU-course after transplantation.

• Early (<30 days post-transplant) post-operative death

• Major suture problems (airway stenosis or stent)

• Retransplantation (lung)

• Previous transplantation (solid organ)

• Multi-organ transplantation (lung+ other solid organ)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Bronchiolitis Obliterans Syndrome
• Graft Rejection
• Lymphocytic Bronchiolitis
• Respiratory Infection
• Respiratory Tract Infections

Intervention

Drug:
• Azithromycin
Azithromycin 250 mg daily during 5 days followed by 250 mg three times a week on Mon., Wed. and Fri. during study-period.
• Placebo
Placebo once daily during 5 days, followed by one placebo three times a week on Mon., Wed. and Fri during rest of study-period.

Locations

Country	Name	City	State
Belgium	Katholieke Universiteit Leuven and University Hospital Gasthuisberg	Leuven

Sponsors (3)

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

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of Bronchiolitis Obliterans Syndrome (BOS)	BOS was defined as a sustained decrease in forced Expiratory Volume in one second (FEV1) of at least 20% from the patient's maximum post-operative values in the absence of other causes.	2 years post-transplant	No
Primary	Overall Survival	Survival data were obtained using all-cause mortality information in the Leuven University Hospital transplant database, in which all our lung transplant recipients since 1991 are registered. For the end-point of all-cause mortality, survival times were not censored at retransplantation or at study-discontinuation if these preceded death, or else at 2 years after transplantation.	2 years post-transplant	No
Secondary	Acute Rejection Incidence Rate	Bronchoscopy and broncho-alveolar lavage (BAL) was routinely performed at discharge, 3, 6, 12, 18, 24 months post-transplantation and later at intervals of 1 year, or in case of clinically suspected acute allograft rejection, infection or chronic rejection. Transbronchial biopsies were routinely performed at discharge and 3 months post-transplant or in case of suspected acute rejection, infection or chronic rejection. Biopsies were graded according to the 1996 ISHLT-guidelines (grade A0-4 with concomitant B0-4), as well as assessed for other interstitial lesions of the pulmonary graft.	2 years post-transplant	No
Secondary	Infection Incidence Rate	Cytomegalovirus (CMV)-status was assessed on on every broncho-alevolar lavage sample and by serum CMV DNA at weekly intervals during hospitalization and thereafter at each outpatient evaluation or hospital admission. Immunohistochemical staining for CMV was performed on transbronchial biopsies in case of clinical suspicion of infection (i.e. dyspnea, cough, sputum, fever, increased plasma C-reactive protein, new chest radiograph infiltrates, or a decrease of at least 10% in peak expiratory flow (PEF) as measured by patient's peak flow measurements.	2 years post-transplant	No
Secondary	Pulmonary Function	Spirometry (Masterscreen, Jaeger, Hoechberg, Germany) was performed at twice weekly intervals for the first 2 postoperative months, thereafter at weekly to biweekly intervals until 6 months post-transplantation, then every 2 to 4 weeks until the first postoperative year and afterwards life-long at intervals of 2 to 3 months according to American Thoracic Society standards and forced expiratory volume in one second (FEV1) expressed in terms of the percentage of predicted values.	during first two years post-transplant	No
Secondary	Broncho-alveolar (BAL) Neutrophilia	BAL was performed with two 50 mL aliquots of sterile saline at room temperature. Five mL of the recovered BAL fluid was sent for microbiological and virological assessment, whereas the remaining fluid was analysed for cell counts after a cytospin was made in a Shandon cytocentrifuge and stained with May-Grünwald-Giemsa. Differential cell counts were determined by counting at least 300 cells.	during first two years post-transplant	No
Secondary	Plasma C-reactive Protein (CRP) Levels	Plasma C-reactive protein (CRP) levels were assessed using Tina-quant CRP latex assay, Roche, Mannheim, Germany; sensitivity threshold of 1 mg/L, upper limit of normal 5 mg/L.	during the first two years post-transplant	No