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 Decline of FEV1 ≥10% From Pre Transplantation

NCT04655508 | Terminated Phase 3

• 1 other identifier: APHP180600
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Stem Cell Transplant Complications; Respiratory Disease; Bronchiolitis Obliterans

Outcome Measures

Primary Outcomes (1)

• FEV: Forced Expiratory Volume in 1 second

  The primary criterion will be the change in the FEV1% predicted value from inclusion to 6 months following the initiation of treatment

  The primary criterion will be measured at months 0, 1, 3, 6, 9 and 12.

Secondary Outcomes (12)

• Graft Versus Host Disease

  The criterion will be measured at months 0, 1, 3, 6, 9 and 12.

• Dyspnea

  The criterion will be measured at months 0, 1, 3, 6, 9 and 12.

• Step Test

  The criterion will be measured at months 0, 1, 3, 6, 9 and 12.

• Bronchiolitis Obliterative Syndrome

  The criterion will be measured at months 0, 1, 3, 6, 9 and 12.

• Adverse events

  The criterion will be measured at months 0, 1, 3, 6, 9 and 12.

Study Arms (2)

Seretide

EXPERIMENTAL

For children between 6 to 11 years (\< 12 years): 50 μg inhaled fluticasone propionate and 25 μg salmeterol (SERETIDE® 50/25) :two puffs twice a day from randomisation during 6 months using inhalation chamber \- For children between 12 to 17 years (\> or = 12 years) : 125 μg inhaled fluticasone propionate and 25 μg salmeterol (SERETIDE® 125/25): two puffs twice a day from randomisation during 6 months using inhalation chamber

Drug: Seretide

placebo

PLACEBO COMPARATOR

For children between 6 to 11 years (\< 12 years): placebo of SERETIDE® 50/25 :two puffs twice a day from randomisation during 6 months using inhalation chamber For children between 12 to 17 years (\> or = 12 years) : placebo of SERETIDE® 125/25: two puffs twice a day from randomisation during 6 months using inhalation chamber

Drug: Placebo

Interventions

Seretide DRUG

For children between 6 to 11 years (\< 12 years): 50 μg inhaled fluticasone propionate and 25 μg salmeterol (SERETIDE® 50/25) :two puffs twice a day from randomisation during 6 months using inhalation chamber \- For children between 12 to 17 years (\> or = 12 years) : 125 μg inhaled fluticasone propionate and 25 μg salmeterol (SERETIDE® 125/25): two puffs twice a day from randomisation during 6 months using inhalation chamber

Seretide

Placebo DRUG

For children between 6 to 11 years (\< 12 years): placebo of SERETIDE® 50/25 :two puffs twice a day from randomisation during 6 months using inhalation chamber For children between 12 to 17 years (\> or = 12 years) : placebo of SERETIDE® 125/25: two puffs twice a day from randomisation during 6 months using inhalation chamber

placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Houdouin véronique

Paris, 75019, France

Location

MeSH Terms

Conditions

Respiration Disorders; Bronchiolitis Obliterans

Interventions

Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Bronchiolitis; Bronchitis; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: December 7, 2020
• Study Start: May 21, 2021
• Primary Completion: September 27, 2023
• Study Completion: September 27, 2023
• Last Updated: September 16, 2025

Record last verified: 2024-02

Locations

FR (1)