Clinical trial NCT00624754: Prospective Evaluation of the Efficacy of Budesonide/Formoterol in Bronchiolitis Obliterans in AHSCT
Official title: recipientsProspective Evaluation of the Efficacy of Budesonide/Formoterol (Symbicort®) in Bronchiolitis Obliterans in Allogeneic Haematopoietic Stem Cell Transplantation (AHSCT) Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obstructive Airway Disease
Keywords: Obstructive airway disease
bronchiolitis obliterans
allogeneic hematopoietic stem cell transplantation
bone marrow transplantation
inhaled treatment
Budesonide Formoterol
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2008-02-27
Enrollment: 32
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: The primary endpoint is based on pulmonary function tests (PFT): the absolute variation of FEV1 after 1 month of treatment will be assessed.
timeFrame: 1 month
Secondary outcomes:
measure: 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
timeFrame: 1, 6 and 7 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Saint Louis
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Anne BERGERON
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.