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

Obstructive Airway Disease Clinical Trial

— Alloforb  

Official title:

recipientsProspective Evaluation of the Efficacy of Budesonide/Formoterol (Symbicort®) in Bronchiolitis Obliterans in Allogeneic Haematopoietic Stem Cell Transplantation (AHSCT) Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00624754
• Other study ID #: P070116
• Status: Completed
• Phase: Phase 2
• First received: February 15, 2008
• Last updated: May 3, 2013
• Start date: March 2008
• Est. completion date: July 2012

Study information

• Verified date: January 2009
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Lung Diseases, Obstructive
• Obstructive Airway Disease

Intervention

Drug:
• Formoterol/Budesonide
Budesonide/Formoterol 400/12: 800 µg b.i.d for 1 month
• lactose
Lactose 2 puffs b.i.d for 1 month

Locations

Country	Name	City	State
France	Hôpital Saint Louis	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	AstraZeneca

Country where clinical trial is conducted

France, 

References & Publications (1)

Bergeron A, Belle A, Chevret S, Ribaud P, Devergie A, Esperou H, Ades L, Gluckman E, Socié 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. Epub 2007 Mar 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No