Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation (ALLOZITHRO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01959100
First received: October 7, 2013
Last updated: May 22, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Malignant Hematological Diseases
Drug: Azithromycin
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Airflow obstruction (AFO)-free survival [ Time Frame: 2 year after allogeneic HSCT ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 forced vital capacity (FVC), residual volume (RV), 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 ]

Estimated Enrollment: 460
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)
Arms Assigned Interventions
Experimental: Azithromycine
250 mg x 3/week during a meal for a period of 2 years
Drug: Azithromycin
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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01959100

Contacts
Contact: Anne Bergeron-Lafaurie, MD PhD +33 1 42 49 41 66 anne.bergeron-lafaurie@sls.aphp.fr

Locations
France
Saint Louis Recruiting
Paris, Ile de France, France, 75010
Contact: Anne Bergeron-Lafaurie, MD PhD    +33 1 42 49 41 66    anne.bergeron-lafaurie@sls.aphp.fr   
Principal Investigator: Anne bergeron-Lafaurie, MD PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01959100     History of Changes
Other Study ID Numbers: P120110
Study First Received: October 7, 2013
Last Updated: May 22, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
hematopoietic stem cell transplantation
pulmonary non-infectious complications
bronchiolitis obliterans syndrome

Additional relevant MeSH terms:
Bronchial Diseases
Bronchiolitis
Bronchiolitis Obliterans
Hematologic Diseases
Bronchitis
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 August 20, 2014