Phosphodiesterase-type 5 inhibitors in adult and adolescent patients with univentricular heart disease: a multi-center, randomized, double blind phase III study

Phase 1

• Conditions: adult and adolescent patients with univentricular heart diseases and pulmonary arterial pressure; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2018-004828-11-FR
• Lead Sponsor: niversity Hospital of Montpellier

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-29
• Last Update Posted: 17 January 2022

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1.15 years of age and over.
2.Patient’s weight over 20 kg
3.Patients with CHD with a single ventricular type defined by the classification of congenital heart diseases in Orphanet [50].
4.PAH defined by diagnostic catheterization with mean PAP > 15 mmHg and a trans-pulmonary gradient > 5 mmHg, performed as part of the usual follow-up. No definition of PAH in SV is available as a result of a particular physiology. Therefore, we chose the 15mmHg cut-off, which is used in clinical routine to allow or contra-indicate the Fontan procedure [50,51].
5.Appropriate written informed consent (adult patients, legal parents for teenagers), and formal assent (teenagers), should to be provided.
6.Beneficiary of a health insurance.

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patient who is unable to perform a cardio-pulmonary exercise test.
2.Cardiac surgery planned during the trial.
3.Patient treated by any pulmonary arterial vasodilator drug, as defined in the 2015 PH guidelines [49], within 6 months before inclusion, regardless the duration and the type(s) (oral, intravenous, subcutaneous, inhaled) of administration.
4.Patient treated by Sildenafil or any other type of phosphodiesterase--type 5 inhibitor (such as tadalafil) within 6 months before inclusion, regardless the duration of administration.
5.Interventional cardiac catheterization planned during the trial (collateral occlusion, fenestration occlusion, stenting, angioplasty, ablation of rhythm disorder), other than during the screening.
6.Participation in another clinical trial or administration of an off-label drug in the 4 weeks preceding the screening.
7.Pregnancy, desire for pregnancy, absence of contraception during the study period.
8.Severe hepatic insufficiency (Child-Pugh C class).
9.Hypersensitivity to the active substance or to any of the excipients of the tablet: microcrystalline cellulose, calcium hydrogen phosphate anhydrous, croscarmellose sodium, stearate of magnesium, hypromellose, titanium dioxide (E171), monohydrate lactose, glycerol triacetate.
10.Combination with products called nitric oxide donors (such as amyl nitrite) or with nitrates in any form, due to the hypotensive effects of nitrates.
11.Concomitant administration of PDE5 inhibitors, such as Sildenafil, with guanylate cyclase stimulators, such as Riociguat.
12.Combination with the most potent inhibitors of CYP3A4 (eg ketoconazole, itraconazole, ritonavir)
13.Disposition to priapism, sclerosis of corpora cavernosa, disease of La Peyronie, sickle cell anemia, multiple myeloma, leukemia.
14.Uncontrolled hypotension or risk of hypotension: water depletion, obstruction to ejection of the left ventricle, dysfunction of the autonomic nervous system, patient under alpha-blocker.
15.Severe cardiovascular events, recent (<3 months) or not stabilized: myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage.
16.Active hemorrhagic disorders.
17.Active gastro-duodenal ulcer.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified