Efficacy of Fluticasone Propionate Associated With Salmeterol Using Inhalation Chamber Versus Placebo to Improve the Respiratory Function in Children Over Six Years of Age Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation With a Decli

• Status: Recruiting
• Trial end date: 2024-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Bronchiolitis Obliterative Syndrome (BOS) is the primary noninfectious pulmonary complication after hematopoietic stem cell transplantation (HSCT) and usually carries a poor prognosis. It occurs in about 10% of children underwent HSCT. The National Institutes of Health (NIH) published guidelines and criteria for the diagnosis of BOS. BOS defined by spirometric criteria according to modified NIH consensus guidelines: FEV1 < 75% predicted and a greater than 10% decline from pretransplant baseline, and FEV1/FVC <0.7 (FCV: Forced Vital Capacity). Nevertheless Cheng and al. indicate that the magnitude of FEV1 decline before diagnosis exceeded the diagnostic requirement of a greater than 10% decline compared with baseline FEV. Moreover, the decline in FEV1 prior to BOS diagnosis appeared to occur within 6 months for those patients. Recent studies suggest that any intervention should be targeted during the FEV1 decline, and before the diagnosis of BOS. For this, inhalated treatment are used: Bergeron et al. reported improvements in symptoms as well in FEV1 one month followed treatment including formoterol and budesonide in a prospective trial including adults (12% increase of FEV1 for 62% adults). Williams and al. in another prospective adult's cohort, showed that the association between fluticasone, montelukast and azythromycin was associated with stable lung function, reduced systemic corticosteroids, and improved quality of life at 3 months for adults with BOS.

In our national French prospective cohort which include 300 children with HSCT from 2014 to 2017 (RESPPEDHEM Programme Hospitalier de Recherche Clinique 2012), 35% of children presented a decline of FEV1≥ 10% without BOS criteria (FEV1 < 75% and FEV1/FVC <0.7). Among them, some received combination of corticoids and long acting beta agonists for 6 months. Children with this type of inhalated treatment improved their FEV1 to 88.1% predicted while children without any treatment have a FEV1 at 80.7% predicted. Our hypothesis is that association of Fluticasone Propionate and Salmeterol can be used as a treatment of the decline of FEV1 for children and so prevent BOS.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: GlaxoSmithKline
• Treatments: Fluticasone-Salmeterol Drug Combination

Criteria

Inclusion Criteria:

• 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 (social security 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 Bronchiolitis Obliterative Syndrome international criteria, neither initiation of inhaled treatment from transplantation to randomization visit.

Exclusion Criteria:

• 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

• Patients with hypersensitivity to the active substances: salmeterol, fluticasone propionate, or to the excipients: norflurane.

Non-Randomisation criteria :

• Viral respiratory infection (fever ≥ 38°C, tachypnea according to age, positive viral PCR (Polymerase Chain Reaction) pharyngeal aspiration) during the last month;

• Lower respiratory tract infection (fever ≥ 38°C, tachypnea, radiologically or echography confirmed pneumonia, sputum) during the last month;

• Invasive fungal disease (as defined by European Organisation for Research and Treatment of Cancer/Mycoses Study Group consensus group) during the last month.

• Potent cytochrome P450 3A4 inhibitors, such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir and nefazodone.

• Corticosteroids or bronchodilatators inhaled treatment after transplantation

• Bronchiolitis Obliterative Syndrome