Bronchiolitis Obliterative Syndrome after hematopoietic stem cell transplantation (HSCT). .
Conditions
Interventions
Trade Name: SERETIDE 125 microgrammes/25 microgrammes/dose, suspension pour inhalation en flacon pressurisé avec valve doseuse
Pharmaceutical Form: Inhalation solution
Pharmaceutical form of the place
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria before HCST : - Children and adolescent aged 6 to 17 years - Getting an Allo Hematopoietic cell stem transplantation - Provide written informed consent from legal guardian - Covered by medical insurance (sécurité sociale ou CMU). Randomisation criteria: - Decline of FEV1 = 10% from pre transplantation between M3 and M12 after the transplantation, confirmed over two functional test performed one week apart, without BOS international criteria, neither initiation of inhaled treatment from transplantation to randomization visit. Are the trial subjects under 18? yes Number of subjects for this age range: 243 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Non-Inclusion criteria before HSCT : Patients with no affiliation to a social security scheme (beneficiary or legal) Pregnancy Asthma defined by reversibility with salbutamol (FEV1 > 12% or FEV1> 200ml) under inhaled corticosteroids or long acting beta agonists during the last three months Non-Randomisation criteria : - Viral respiratory infection (fever = 38°C, tachypnea according to age, positive viral PCR pharyngeal aspiration) during the last month; - Lower respiratory tract infection (fever = 38°C, tachypnea, radiologicaly or echography confirmed pneumonia, sputum) during the last month; - Invasive fungal disease (as defined by EORTC/MSG consensus group) during the last month. - Potent cytochrome P450 3A4 inhibitors, such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nilfinavir and nefazodone. - Corticosteroids or bronchodilatators inhaled treatment after transplantation - BOS
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of a Fluticasone Propionate associated with Salmeterol using inhalation chamber compared to placebo on respiratory function at 6 months in children over six years of age who underwent allogeneic hematopoietic stem cell transplantation with a decline of FEV1 = 10% from pre transplantation during the first year after transplantation. ;Secondary Objective: To assess the effect of a Fluticasone Propionate associated with Salmeterol using inhalation chamber compared to placebo in children over six years old underwent allogeneic hematopoietic stem cell transplantation with a decline of FEV1 = 10% from pre transplantation to 6 months following the initiation of the treatment on pulmonary function, respiratory symptoms, Bonchiolitis Obliterative Syndrome (BOS) rate, oral steroid exposure and the occurrence of infections.;Primary end point(s): The primary criterion will be the difference in the FEV1% predicted value from inclusion to 6 months following the initiation of treatment. ;Timepoint(s) of evaluation of this end point: 6 Months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1)Endpoints relative to respiratory symptoms : * dyspnea will be evaluate at the NYHA scoring; * step test (patient climb up and down step during three minutes at the frequency of 30/mn) : Respiratory rate, dyspnea Heart rate, SaO2 during the exercise. 2) Endpoints relative to pulmonary function : * FEV1 (Forced expiratoy volume) VC (Vital Capacity) , TLC (Total Lung capacity) , RV (Residual volume), FRC (Functional Residual Capacity), sRaw (specific airway resistance) DLCO (diffusing capacity of the lungs) using a similar method of measurement for static lung volumes (plethysmography) * Number of patients presented with BOS defined as the absence of infection, and FEV1 120% or air trapping or bronchiectasies or small airways thyckening on computed tomography 3) Endpoints relative to GVHD : * Acute and Chronic GVHD manifestations defined on NIH consensus with scoring; * First line of treatment: cumulative dose of corticosteroid systemic exposure and cumulative dose of calcineurins inhibitors. * Second line of GVHD treatment exposure will be assed using the other type of treatment. 4) Endpoints relative to respiratory infections : - Number of adverse events. 5) Endpoints relative to safety and tolerance: - Adverse events during the study period such as treatment tolerance, thrush, death. ;Timepoint(s) of evaluation of this end point: 12 Months | — |
Countries
France
Contacts
Public ContactDRCI Hopital Saint louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Outcome results
None listed