Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV‐INHIBITION study design

Abstract

AimsIn 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. We present the SV-INHIBITION study rationale, design, and methods. Methods and resultsThe SV-INHIBITION trial is a nationwide multicentre, randomized, 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 years old) with an SV. Patients with a mean pulmonary arterial pressure >15 mmHg and a trans-pulmonary gradient >5 mmHg, measured by cardiac catheterization, will be eligible. The primary outcome is the variation of the VE/VCO 2 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/VCO 2 slope, with a power of 90% and an alpha risk of 5%. The secondary outcomes are clinical outcomes, oxygen saturation, 6 min walk test, SV function, NT-proBNP, peak VO 2 , stroke volume, mean pulmonary arterial pressure, trans-pulmonary gradient, SF36 quality of life score, safety, and acceptability. Conclusions The SV-INHIBITION study aims to answer the question whether PDE5 inhibitors should be prescribed in patients with an SV. This trial has been built focusing on the three levels of research defined by the World Health Organization: disability (exercise tolerance), deficit (SV function), and handicap (quality of life).

2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

“…While some series have reported promising results, there have been cases where therapies were not tolerated [581]. Similarly, using PAH therapies in Fontan circulation has yielded conflicting results, and results of further studies are awaited [582][583][584].…”

Focused Update on Pulmonary Hypertension in Children—Selected Topics of Interest for the Adult Cardiologist

“…Of note, there is only one "longer" term randomized, double blind, cross over trial investigating the effects of sildenafil over 6 weeks [ 76 ]. The SV INHIBITION study (NCT03997097), a French multicentre, randomized, double blind, placebo-controlled Phase III study was designed and is currently starting enrolment [ 80 ]. Results of this important trial will hopefully answer the question whether PDE5 should be routinely used in suitable Fontan patients.…”

Impact of COVID-19 disease on clinical research in pediatric and congenital cardiology

“…Therefore, recent regulatory initiatives have modified the pediatric clinical trials landscape by significantly increasing capital investment and trial volume in pediatric cardiology [4] . As a result, advances in evidence-based medicine are progressively emerging in pediatric and congenital cardiology [5] , [6] , [7] and research protocols dedicated to patients with CHD are being increasingly published [8] , [9] , [10] , [11] , [12] , [13] . To note, for children with the most severe conditions, such as pulmonary hypertension, being enrolled in a clinical trial may represent a real promising opportunity [14] , [15] , [16] .…”