Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation (ALLOZITHRO)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Evaluation of the Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation|
- Airflow decline (AFD)-free survival [ Time Frame: 2 year after allogeneic HSCT ] [ Designated as safety issue: No ]Defined on the criteria from Chien JW et al (Am J Resp Crit Care Med 2003;168:208-14) by an annualized decline of percent predicted forced expiratory volume in 1 second (FEV1) of more than 5%
- Overall survival [ Time Frame: within 2 years of inclusion ] [ Designated as safety issue: No ]
- Occurrence of late-onset pulmonary non-infectious complications (=bronchiolitis obliterans syndrome, SBO) [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]bronchiolitis obliterans syndrome (SBO) is defined as the absence of infection with an forced expiratory volume in 1 second (FEV1) of <75% of predicted or a decline of > 10% and FEV1/Slow vital capacity (SVC) < 0.7 or residual volume (RV) or RV/total lung capacity (TLC) > 120%, and interstitial lung disease, which is defined as the onset of new interstitial lung abnormalities observed with a lung CT scan and the absence of infection.
- Variation of pulmonary function testing parameters [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]variation in mean forced expiratory volume in 1 second (FEV1) decline, forced vital capacity (FVC), residual volume (RV), Total Lung capacity (TLC), Forced expiratory flow at 25% point to the 75% point of Forced Vital Capacity (FEF25-75%) as compared to baseline values (at inclusion)
- Occurrence of acute and chronic extra-thoracic graft versus host disease (GVHD) [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]
- Quality of life [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]
- Tolerance [ Time Frame: within 2 years of inclusion ] [ Designated as safety issue: Yes ]adverse events
- Cumulative dose of steroids treatment [ Time Frame: within the 2 years after inclusion ] [ Designated as safety issue: No ]
|Study Start Date:||February 2014|
|Estimated Study Completion Date:||February 2018|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
250 mg x 3/week during a meal for a period of 2 years
250 mg x 3/week per os during a meal for a period of 2 years
Placebo Comparator: Placebo
250 mg x 3/week during a meal for a period of 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01959100
|Paris, Ile de France, France, 75010|