Azithromycin in Bronchiolitis Obliterans Syndrome (AZI001)

This study has been completed.
Sponsor:
Collaborators:
University Hospital, Gasthuisberg
Fund for Scientific Research, Flanders, Belgium
Information provided by:
Katholieke Universiteit Leuven
ClinicalTrials.gov Identifier:
NCT01009619
First received: November 6, 2009
Last updated: August 29, 2011
Last verified: August 2011
  Purpose

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


Condition Intervention Phase
Bronchiolitis Obliterans Syndrome
Graft Rejection
Lymphocytic Bronchiolitis
Respiratory Infection
Drug: Azithromycin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized Double-blind Placebo-controlled Prevention Trial of Azithromycin in Lung Transplantation.

Resource links provided by NLM:


Further study details as provided by Katholieke Universiteit Leuven:

Primary Outcome Measures:
  • Prevalence of Bronchiolitis Obliterans Syndrome (BOS) [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Acute Rejection Incidence Rate [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: No ]
    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.

  • Infection Incidence Rate [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: No ]
    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.

  • Pulmonary Function [ Time Frame: during first two years post-transplant ] [ Designated as safety issue: No ]
    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.

  • Broncho-alveolar (BAL) Neutrophilia [ Time Frame: during first two years post-transplant ] [ Designated as safety issue: No ]
    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.

  • Plasma C-reactive Protein (CRP) Levels [ Time Frame: during the first two years post-transplant ] [ Designated as safety issue: No ]
    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.


Enrollment: 83
Study Start Date: September 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azithromycin
250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study
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.
Other Name: Zitromax (Azithromycin Dihydrate, Pfizer, ZTM250)
Placebo Comparator: Placebo
PLacebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Drug: 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.
Other Name: Lactose monohydricum Ph.Eur. (Fagron)

Detailed 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.
  Eligibility

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

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)
  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: NCT01009619

Locations
Belgium
Katholieke Universiteit Leuven and University Hospital Gasthuisberg
Leuven, Belgium, B-3000
Sponsors and Collaborators
Katholieke Universiteit Leuven
University Hospital, Gasthuisberg
Fund for Scientific Research, Flanders, Belgium
Investigators
Principal Investigator: Geert M Verleden, Prof. Dr. KULeuven and University Hospitals Leuven
  More Information

No publications provided by Katholieke Universiteit Leuven

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Dr. GM. Verleden, KULeuven and University Hospital Leuven
ClinicalTrials.gov Identifier: NCT01009619     History of Changes
Other Study ID Numbers: AZI001, EudraCT ref. 2005-003893-46
Study First Received: November 6, 2009
Results First Received: April 21, 2011
Last Updated: August 29, 2011
Health Authority: European Union: European Medicines Agency
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by Katholieke Universiteit Leuven:
Bronchiolitis Obliterans Syndrome
Acute allograft Rejection
Lymphocytic bronchiolitis
Respiratory infection
Survival
Mortality
Pulmonary function
FEV1
Broncho-alveolar lavage
Neutrophils
Interleukin
Culture
Azithromycin

Additional relevant MeSH terms:
Infection
Bronchiolitis
Respiratory Tract Infections
Bronchiolitis Obliterans
Syndrome
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Disease
Pathologic Processes

ClinicalTrials.gov processed this record on September 22, 2014