Prospective Evaluation of the Efficacy of Budesonide/Formoterol in Bronchiolitis Obliterans in AHSCT

NCT00624754 | Completed Phase 2 DMC

• 1 other identifier: P070116
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The usual treatment for obstructive airway disease (OAD) after allogeneic hematopoietic stem cell transplantation (AHSCT) , which is related to graft versus host disease (GVHD), consists of intensification of systemic immunosuppressive therapy.

Conditions

Obstructive Airway Disease

Keywords

Obstructive airway disease; bronchiolitis obliterans; allogeneic hematopoietic stem cell transplantation; bone marrow transplantation; inhaled treatment; Budesonide Formoterol

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is based on pulmonary function tests (PFT): the absolute variation of FEV1 after 1 month of treatment will be assessed.

  1 month

Secondary Outcomes (1)

• Improvement or stabilisation of FEV1; Prevalence of improvement of FEV1 by at least 200 ml and 12% at 1 month compared to baseline; Variation of FEF 25-75% and vital capacity; Quality of life measurement; Evaluation of the clinical score

  1, 6 and 7 months

Study Arms (2)

1

EXPERIMENTAL

Patients with OAD will receive Symbicort® at the dose of two puffs morning and evening, each delivering 400/12 µg of budesonide/formoterol. Symbicort® will be administered by inhalation using the Turbuhaler (TH) system

Drug: Formoterol/Budesonide

2

PLACEBO COMPARATOR

Patients with OAD will receive lactose as a placebo, administered by inhalation using the Turbuhaler (TH) system

Drug: lactose

Interventions

Formoterol/Budesonide DRUG

Budesonide/Formoterol 400/12: 800 µg b.i.d for 1 month

1

lactose DRUG

Lactose 2 puffs b.i.d for 1 month

2

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥16 years.
• Previous normal PFTs available.
• Absence of extrathoracic GVH disease justifying initiation or intensification of systemic immunosuppressive therapy.
• Respiratory signs present for less than 6 months.
• AHSCT recipients who have developed moderate to severe bronchiolitis obliterans, defined by reduction of FEV1/VC below the 5th percentile of predicted normal or \< 80% of predicted, with FEV1 \< 80% of predicted and ≥ 40% of predicted, not reversible after inhalation of short-acting beta-2 agonist. AHSCT recipients with FEV1 \< 80% of predicted and ≥ 40% of predicted, not reversible after inhalation of short-acting beta-2 agonist and TLC ≥ 80% of predicted.
• Respiratory symptoms related to obstructive lung disease present for at least 6 months.
• Negative respiratory microbiology work-up.
• Informed consent signed by the patient or both parents of a minor.

You may not qualify if:

• Extrathoracic graft versus host reaction justifying initiation or intensification of systemic immunosuppressive therapy.
• Known intolerance to inhaled bronchodilators and/or corticosteroids and/or lactose.
• Personal or donor history of asthma.
• Active smoking
• FEV1 \< 40% of predicted normal or ≥ 80% of predicted normal or PO2 \< 50 mmHg.
• Documented respiratory tract infection.
• Pregnancy.
• Absence of effective contraception during the trial.
• Not covered by French national health insurance.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• AstraZeneca: collaborator

Study Sites (1)

Hôpital Saint Louis

Paris, 75010, France

Location

Related Publications (2)

• Bergeron A, Belle A, Chevret S, Ribaud P, Devergie A, Esperou H, Ades L, Gluckman E, Socie G, Tazi A. Combined inhaled steroids and bronchodilatators in obstructive airway disease after allogeneic stem cell transplantation. Bone Marrow Transplant. 2007 May;39(9):547-53. doi: 10.1038/sj.bmt.1705637. Epub 2007 Mar 12.

  PMID: 17351647 BACKGROUND

• 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: 25835160 DERIVED

MeSH Terms

Conditions

Lung Diseases, Obstructive; Bronchiolitis Obliterans

Interventions

Formoterol Fumarate; Budesonide; Lactose

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Bronchiolitis; Bronchitis; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Anne BERGERON

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2008
• First Posted: February 27, 2008
• Study Start: March 1, 2008
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: May 6, 2013

Record last verified: 2009-01

Locations

FR (1)