Overview

This trial is active, not recruiting.

Condition malignant hematological diseases
Treatments azithromycin, placebo
Phase phase 3
Sponsor Assistance Publique - Hôpitaux de Paris
Start date February 2014
End date February 2017
Trial size 480 participants
Trial identifier NCT01959100, P120110

Summary

The occurrence of bronchiolitis obliterans syndrome (SBO) after allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be a chronic pulmonary graft versus host disease (GVHD) that is associated with significant mortality and morbidity. The reported incidence of SBO varies from 6 to 26% of allogeneic HSC recipients and is usually diagnosed within 2 years after transplantation. The diagnosis of SBO relies on the occurrence of a new airflow obstruction identified during pulmonary function testing, and the definition differs between studies. Currently, no curative immunosuppressive treatment is available, and recent data suggest that the use of these treatments, especially corticosteroids, should be limited because of their toxicity. The impairment of lung function parameters is likely caused by fibrous small airway lesions. Few data on the pathogenesis of SBO after allogeneic HSCT are available. Several hypotheses are based on the occurrence of SBO during chronic graft rejection after lung transplantation, which shares many clinical and histopathological similarities with SBO after allogeneic HSCT. One hypothesis is that the first step leading to SBO is lung epithelium injury. SBO is then identified as an alloimmune reaction with only one clearly identified risk factor: extrathoracic chronic GVHD. Due to their anti-inflammatory and immunomodulatory properties, recent data suggest that low-dose macrolides may be effective at preventing SBO after lung transplants. This well-tolerated treatment may be useful for preventing SBO after allogeneic HSCT.

The objective of this Phase 3 multicentre randomized, double-blinded, clinical trial is to evaluate the efficacy of azithromycin in preventing BO syndrome after allogeneic HSCT in patients with malignant hematological diseases.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Experimental)
250 mg x 3/week during a meal for a period of 2 years
azithromycin
250 mg x 3/week per os during a meal for a period of 2 years
(Placebo Comparator)
250 mg x 3/week during a meal for a period of 2 years.
placebo
250 mg x 3/week during a meal for a period of 2 years

Primary Outcomes

Measure
Airflow decline (AFD)-free survival
time frame: 2 year after allogeneic HSCT

Secondary Outcomes

Measure
Overall survival
time frame: within 2 years of inclusion
Occurrence of late-onset pulmonary non-infectious complications (=bronchiolitis obliterans syndrome, SBO)
time frame: within 2 years after inclusion
Variation of pulmonary function testing parameters
time frame: within 2 years after inclusion
Occurrence of acute and chronic extra-thoracic graft versus host disease (GVHD)
time frame: within 2 years after inclusion
Quality of life
time frame: within 2 years after inclusion
Tolerance
time frame: within 2 years of inclusion
Cumulative dose of steroids treatment
time frame: within the 2 years after inclusion

Eligibility Criteria

Male or female participants at least 16 years old.

Inclusion Criteria: - Patients> 16 years old - Experimenting an allogeneic HSCT for a hematologic malignancy - Pre-transplantation Pulmonary Function Testing - With written informed consent Exclusion Criteria: - Allergy or Intolerance to azithromycin, macrolides or ketolide or excipient - Prolonged corrected QT (QTc) interval (>450 msec) - Taking medications that prolong the QTc interval (Cisapride, ergotamine, dyhydroergotamine) - Taking ergotamine and dyhydroergotamine due to the risk of ergotism - Family history of a prolonged QTc interval. - History of congestive heart failure - Taking colchicine Severe liver insufficiency • History of infection due to atypical mycobacteria

Additional Information

Official title Evaluation of the Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.