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

NCT ID: NCT00624754

Last Updated: 2013-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2012-07-31

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.

Detailed Description

Although it has not been evaluated prospectively, 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. However, this treatment has a limited efficacy and is associated with a significant number of serious adverse effects, particularly infectious. Alternative treatments are therefore necessary.We have retrospectively reported clinical and functional improvement in patients with OAD following AHSCT treated with inhaled budesonide/formoterol combination.These encouraging results need to be confirmed by the present randomised, prospective double-blind trial. This study is therefore designed to evaluate the efficacy of budesonide/formoterol versus placebo in patients with moderate to severe OAD, not requiring initiation or intensification of systemic immunosuppressive therapy for extra thoracic GVHD.

Inclusion criteria modified according to amendment of 02/11/2009

Conditions

Obstructive Airway Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

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

Group Type: EXPERIMENTAL

Formoterol/Budesonide

Intervention Type: DRUG

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

2

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

Group Type: PLACEBO_COMPARATOR

lactose

Intervention Type: DRUG

Lactose 2 puffs b.i.d for 1 month

Interventions

Formoterol/Budesonide

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

Intervention Type: DRUG

lactose

Lactose 2 puffs b.i.d for 1 month

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Extrathoracic graft versus host reaction justifying initiation or intensification of systemic immunosuppressive therapy.
• Use of inhaled bronchodilator and/or corticosteroid therapy at the time of inclusion.
• 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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne BERGERON

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Saint Louis

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 17351647 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25835160 (View on PubMed)

Other Identifiers

P070116

Identifier Type: -

Identifier Source: org_study_id