NCT03997097

Efficacy of Phosphodiesterase-type 5 Inhibitors in Patients With Univentricular Congenital Heart Disease

Phosphodiesterase-type 5 Inhibitors in Adult and Adolescent Patients With Univentricular Heart Disease: a Multi-center, Randomized, Double Blind Phase III Study

• Status: Withdrawn
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University Hospital, Montpellier · Academic / Other
• Sex: All
• Age: 15 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

In univentricular hearts, selective lung vasodilators such as phosphodiesterase type 5 (PDE5) inhibitors would decrease pulmonary resistance and improve exercise tolerance. However, the level of evidence for the use of PDE5 inhibitors in patients with a single ventricle (SV) remains limited. the investigators present the SV-INHIBITION study rationale, design and methods.The SV-INHIBITION trial is a nationwide multicentre, randomised, double blind, placebo-controlled, phase III study, aiming to evaluate the efficacy of sildenafil on the ventilatory efficiency during exercise, in teenagers and adult patients (\>15 y.o.) with a SV. Patients with pulmonary arterial hypertension (mean pulmonary arterial pressure (mPAP) \> 15 mmHg and trans-pulmonary gradient \> 5 mmHg) measured by cardiac catheterisation, will be eligible. The primary outcome is the variation of the VE/VCO2 slope, measured by a cardiopulmonary exercise test, between baseline and 6 months of treatment. A total of 50 patients are required to observe a decrease of 5 ± 5 points in the VE/VCO2 slope, with a power of 90% power and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, 6 minute walk test, SV function, NT Pro BNP, VO2max, stroke volume, mPAP, trans-pulmonary gradient, SF36 quality of life score, safety and acceptability. This study aims to answer the question whether PDE5 inhibitors should be prescribed in patients with a SV. This trial has been built focusing on the 3 levels of research defined by the WHO: disability (exercise tolerance), deficit (SV function), and handicap (quality of life).

Detailed description

50 Patients with a single ventricle (e.g. univentricular heart), as defined by the ACC-CHD classification, with a mean pulmonary arterial pressure (mPAP) \> 15 mmHg and a trans-pulmonary gradient (TPG) \> 5 mmHg, and aged 15 years old and above, will be prospectively recruited in the participating centres during their regular follow-up. Patients wil be randomised into 2 groups: * Patients randomised in the group 1 will receive sildenafil in 3 oral doses of 20 mg per day (t.i.d.), as defined in the marketing authorization indicated for PAH in adolescent and adult patients, and for a period of 6 months. * Patients in the group 2 will receive a placebo (t.i.d.), for the same period of 6 months. To guarantee the double blind, capsules will be similar in size and colour and will be differentiated only by a vial number regarding to the randomization list. The clinical trials unit of the sponsor's pharmacy will centralize treatment allocation and supply to the participating centres. Drug management (reception, storage, delivery and traceability) will be ensured by the pharmacies of the participating centres. After the 6 month-treatment period, patients will be followed for 3 months, and undergo at least 2 safety visits (1 and 3 months after intervention, and if necessary, any supplementary unscheduled visits). In accordance with the recommendations of the drug notice, the treatment will be suspended progressively over 1 week (20 mg b.i.d for 3 days, then 20 mg q.d. for 4 days, and then stopped) with a reinforcement of the surveillance. Patients will be able to contact an emergency number during this period and the investigator may decide to continue open treatment with sildenafil if clinically justified. The study will be conducted in compliance with the Good Clinical Practices protocol and Declaration of Helsinki principles. It was approved by a drawn National Ethics Committee (CPP) and by the French National Agency of Medicine and Health Products Safety (ANSM). Informed consent will be obtained from all patients and their parents or legal guardians for minors.

Conditions

• Single-ventricle
• Pulmonary Hypertension
• Univentricular Heart

Interventions

Type	Name	Description
DRUG	Sildenafil	Patients randomised in the group 1 will receive sildenafil in 3 oral doses of 20 mg per day
DRUG	Placebos	Patients randomised in the group placebo in 3 oral doses of per day

Timeline

• Start date: 2023-06-01
• Primary completion: 2026-06-01
• Completion: 2028-06-01
• First posted: 2019-06-25
• Last updated: 2023-05-15