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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00624754

Collaborator

AstraZeneca (Industry)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obstructive Airway Disease	Drug: Formoterol/Budesonide Drug: lactose	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Formoterol/Budesonide Budesonide/Formoterol 400/12: 800 µg b.i.d for 1 month
Placebo Comparator: 2 Patients with OAD will receive lactose as a placebo, administered by inhalation using the Turbuhaler (TH) system	Drug: lactose Lactose 2 puffs b.i.d for 1 month

Arm

Intervention/Treatment

Experimental: 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

Drug: Formoterol/Budesonide

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

Placebo Comparator: 2

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

Drug: lactose

Lactose 2 puffs b.i.d for 1 month

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.