NCT01959100

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
480

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Feb 2014

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 7, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 9, 2013

Completed
4 months until next milestone

Study Start

First participant enrolled

February 1, 2014

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
5.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2022

Completed
Last Updated

January 7, 2020

Status Verified

December 1, 2019

Enrollment Period

3.2 years

First QC Date

October 7, 2013

Last Update Submit

January 6, 2020

Conditions

Malignant Hematological Diseases

Keywords

hematopoietic stem cell transplantationpulmonary non-infectious complicationsbronchiolitis obliterans syndrome

Outcome Measures

Primary Outcomes (1)

  • Airflow decline (AFD)-free survival

    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%

    2 year after allogeneic HSCT

Secondary Outcomes (8)

  • Overall survival

    within 2 years of inclusion

  • Occurrence of late-onset pulmonary non-infectious complications (=bronchiolitis obliterans syndrome, SBO)

    within 2 years after inclusion

  • Variation of pulmonary function testing parameters

    within 2 years after inclusion

  • Occurrence of acute and chronic extra-thoracic graft versus host disease (GVHD)

    within 2 years after inclusion

  • Cumulative incidence of hematological relapse

    within the 2 years after inclusion

  • +3 more secondary outcomes

Study Arms (2)

Azithromycine

EXPERIMENTAL

250 mg x 3/week during a meal for a period of 2 years

Drug: Azithromycin

Placebo

PLACEBO COMPARATOR

250 mg x 3/week during a meal for a period of 2 years.

Drug: Placebo

Interventions

AzithromycinDRUG

250 mg x 3/week per os during a meal for a period of 2 years

Azithromycine
PlaceboDRUG

250 mg x 3/week during a meal for a period of 2 years

Placebo

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients\> 16 years old
  • Experimenting an allogeneic HSCT for a hematologic malignancy
  • Pre-transplantation Pulmonary Function Testing
  • With written informed consent

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Saint Louis

Paris, Île-de-France Region, 75010, France

Location

Related Publications (3)

  • Bergeron A, Chevret S, Chagnon K, Godet C, Bergot E, Peffault de Latour R, Dominique S, de Revel T, Juvin K, Maillard N, Reman O, Contentin N, Robin M, Buzyn A, Socie G, Tazi A. Budesonide/Formoterol for bronchiolitis obliterans after hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2015 Jun 1;191(11):1242-9. doi: 10.1164/rccm.201410-1818OC.

    PMID: 25835160RESULT

  • Vallet N, Le Grand S, Bondeelle L, Hoareau B, Corneau A, Bouteiller D, Tournier S, Derivry L, Bohineust A, Tourret M, Gibert D, Mayeur E, Itzykson R, Pacchiardi K, Ingram B, Cassonnet S, Lepage P, Peffault de Latour R, Socie G, Bergeron A, Michonneau D. Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation. Blood. 2022 Dec 8;140(23):2500-2513. doi: 10.1182/blood.2022016926.

    PMID: 35984904DERIVED

  • Bergeron A, Chevret S, Granata A, Chevallier P, Vincent L, Huynh A, Tabrizi R, Labussiere-Wallet H, Bernard M, Chantepie S, Bay JO, Thiebaut-Bertrand A, Thepot S, Contentin N, Fornecker LM, Maillard N, Risso K, Berceanu A, Blaise D, Peffault de La Tour R, Chien JW, Coiteux V, Socie G; ALLOZITHRO Study Investigators. Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):557-566. doi: 10.1001/jama.2017.9938.

    PMID: 28787506DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Organizing PneumoniaBronchiolitis ObliteransBronchiolitisBronchitisBronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesGraft vs Host DiseaseImmune System Diseases

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 7, 2013

First Posted

October 9, 2013

Study Start

February 1, 2014

Primary Completion

April 1, 2017

Study Completion

August 1, 2022

Last Updated

January 7, 2020

Record last verified: 2019-12

Locations

FR(1)