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AzTrials

Malignant Hematological DiseasesPhase 3ALLOZITHRONCT01959100

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

A Phase 3 study testing Azithromycin in people with Malignant Hematological Diseases, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Malignant Hematological Diseases
What is being tested?
Azithromycin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
480 participants
Where
1 siteFrance
Study dates
Feb 2014to Aug 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • Saint Louis

    Paris, Île-de-France Region, 75010

Other trials in France

About this study

Official title: Evaluation of the Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation

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.

Being tested
Azithromycin, Placebo
Keywords
hematopoietic stem cell transplantation, pulmonary non-infectious complications, bronchiolitis obliterans syndrome
Medical subject headings
Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzithromycinDrug

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

  • PlaceboDrug

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

Study groups in NCT01959100
Study groupRoleWhat they receive
AzithromycineExperimental250 mg x 3/week during a meal for a period of 2 years
Receives: Drug: Azithromycin
PlaceboPlacebo comparator250 mg x 3/week during a meal for a period of 2 years.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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%

    Measured: 2 year after allogeneic HSCT

Secondary outcomes (8)

  1. Overall survival

    Measured: within 2 years of inclusion

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

    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.

    Measured: within 2 years after inclusion

  3. Variation of pulmonary function testing parameters

    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)

    Measured: within 2 years after inclusion

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

    Measured: within 2 years after inclusion

  5. Cumulative incidence of hematological relapse

    Measured: within the 2 years after inclusion

  6. Quality of life

    Measured: within 2 years after inclusion

  7. Tolerance

    adverse events

    Measured: within 2 years of inclusion

  8. Cumulative dose of steroids treatment

    Measured: within the 2 years after inclusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2013 (estimated)
  2. Study startFeb 2014
  3. Primary completionApr 2017
  4. Study completionAug 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
480 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01959100
Sponsor's protocol ID
P120110
Acronym
ALLOZITHRO
Status last verified
Dec 2019
First submitted
7 Oct 2013
Last updated
7 Jan 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25835160

  • 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.

    PubMed 35984904

  • 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.

    PubMed 28787506

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Azithromycin in people with Malignant Hematological Diseases, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Airflow decline (AFD)-free survival (time frame: 2 year after allogeneic HSCT). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01959100, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2020.

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