Prospective Evaluation of the Efficacy of Budesonide/Formoterol in Bronchiolitis Obliterans in AHSCT - Full Text View

Sponsor:	Assistance Publique - Hôpitaux de Paris
Collaborator:	AstraZeneca
Information provided by (Responsible Party):	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00624754

Purpose

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	Intervention	Phase
Obstructive Airway Disease	Drug: Formoterol/Budesonide Drug: lactose	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, 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

Resource links provided by NLM:

Drug Information available for: Lactose Formoterol fumarate Budesonide Arformoterol Formoterol Symbicort Arformoterol Tartrate

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

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. [ Time Frame: 1 month ] [ Designated as safety issue: No ]

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 [ Time Frame: 1, 6 and 7 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	32
Study Start Date:	March 2008
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Other Name: Formoterol/Budesonide
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 Other Name: lactose

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.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 1 year.
AHSCT recipients who have developed moderate to severe bronchiolitis obliterans, defined by reduction of FEV1/VC below the 5th percentile of predicted normal, with FEV1 ≤ 70% of predicted normal and ≥ 40% of predicted normal , not reversible after inhalation of short-acting beta-2 agonist.
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 > 70% 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00624754

Contacts

Contact: Anne BERGERON, MD, PhD

+33(0) 1 42 49 96 18

anne.bergeron-lafaurie@sls.aphp.fr

Locations

France
Hôpital Saint Louis	Recruiting
Paris, France, 75010
Contact: Anne BERGERON, MD, PhD +33(0) 1 42 49 96 18 anne.bergeron@sls.aphp.fr
Principal Investigator: Anne Bergeron, MD, PhD

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

AstraZeneca

Investigators

Principal Investigator:

Anne BERGERON

Assistance Publique - Hôpitaux de Paris

More Information

Publications:

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.

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00624754 History of Changes
Other Study ID Numbers:	P070116
Study First Received:	February 15, 2008
Last Updated:	January 18, 2012
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Obstructive airway disease
bronchiolitis obliterans
allogeneic hematopoietic stem cell transplantation

bone marrow transplantation
inhaled treatment
Budesonide Formoterol

Additional relevant MeSH terms:

Bronchiolitis
Bronchiolitis Obliterans
Lung Diseases, Obstructive
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases
Respiratory Tract Infections
Budesonide
Formoterol
Symbicort
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012