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

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ClinicalTrials.gov Identifier: NCT01959100
Recruitment Status : Unknown
Verified December 2019 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was:  Active, not recruiting
First Posted : October 9, 2013
Last Update Posted : January 7, 2020
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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.

Condition or disease Intervention/treatment Phase
Malignant Hematological Diseases Drug: Azithromycin Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 480 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : February 2014
Actual Primary Completion Date : April 2017
Estimated Study Completion Date : August 2022

Arm Intervention/treatment
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.
Drug: Placebo
250 mg x 3/week during a meal for a period of 2 years

Primary Outcome Measures :
  1. Airflow decline (AFD)-free survival [ Time Frame: 2 year after allogeneic HSCT ]
    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%

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: within 2 years of inclusion ]
  2. Occurrence of late-onset pulmonary non-infectious complications (=bronchiolitis obliterans syndrome, SBO) [ Time Frame: within 2 years after inclusion ]
    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.

  3. Variation of pulmonary function testing parameters [ Time Frame: within 2 years after inclusion ]
    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)

  4. Occurrence of acute and chronic extra-thoracic graft versus host disease (GVHD) [ Time Frame: within 2 years after inclusion ]
  5. Cumulative incidence of hematological relapse [ Time Frame: within the 2 years after inclusion ]
  6. Quality of life [ Time Frame: within 2 years after inclusion ]
  7. Tolerance [ Time Frame: within 2 years of inclusion ]
    adverse events

  8. Cumulative dose of steroids treatment [ Time Frame: within the 2 years after inclusion ]

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01959100

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Saint Louis
Paris, Ile De France, France, 75010
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01959100    
Other Study ID Numbers: P120110
First Posted: October 9, 2013    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: December 2019
Keywords provided by Assistance Publique - Hôpitaux de Paris:
hematopoietic stem cell transplantation
pulmonary non-infectious complications
bronchiolitis obliterans syndrome
Additional relevant MeSH terms:
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Bronchiolitis Obliterans
Hematologic Diseases
Respiratory Tract Infections
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Anti-Bacterial Agents
Anti-Infective Agents