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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 : Active, not recruiting
First Posted : October 9, 2013
Last Update Posted : July 23, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE October 7, 2013
First Posted Date  ICMJE October 9, 2013
Last Update Posted Date July 23, 2018
Study Start Date  ICMJE February 2014
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2015)
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%
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2013)
Airflow obstruction (AFO)-free survival [ Time Frame: 2 year after allogeneic HSCT ]
Change History Complete list of historical versions of study NCT01959100 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2016)
  • 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 ]
    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 ]
    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 ]
  • Cumulative incidence of hematological relapse [ Time Frame: within the 2 years after inclusion ]
  • Quality of life [ Time Frame: within 2 years after inclusion ]
  • Tolerance [ Time Frame: within 2 years of inclusion ]
    adverse events
  • Cumulative dose of steroids treatment [ Time Frame: within the 2 years after inclusion ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2013)
  • 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 ]
    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 ]
    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 ]
  • Quality of life [ Time Frame: within 2 years after inclusion ]
  • Tolerance [ Time Frame: within 2 years of inclusion ]
    adverse events
  • Cumulative dose of steroids treatment [ Time Frame: within the 2 years after inclusion ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Official Title  ICMJE Evaluation of the Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Malignant Hematological Diseases
Intervention  ICMJE
  • Drug: Azithromycin
    250 mg x 3/week per os 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
Study Arms  ICMJE
  • Experimental: Azithromycine
    250 mg x 3/week during a meal for a period of 2 years
    Intervention: Drug: Azithromycin
  • Placebo Comparator: Placebo
    250 mg x 3/week during a meal for a period of 2 years.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 20, 2016)
480
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2013)
460
Estimated Study Completion Date  ICMJE August 2020
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01959100
Other Study ID Numbers  ICMJE P120110
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP