Efficacy of Phosphodiesterase-type 5 Inhibitors in Patients With Univentricular Congenital Heart Disease (VU-INHIB)
Single-ventricle, Pulmonary Hypertension, Univentricular Heart
About this trial
This is an interventional treatment trial for Single-ventricle focused on measuring Congenital heart defect, single ventricle, Pulmonary hypertension, sildenafil, pulmonary vasodilator, Eexercise capacity
Eligibility Criteria
Inclusion Criteria:
- 15 years of age and over.
- Patient's weight over 20 kg
- Patients with CHD with a single ventricular type defined by the classification of congenital heart diseases in Orphanet (53).
- 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].
- Appropriate written informed consent (adult patients, legal parents for teenagers), and formal assent (teenagers), should to be provided.
- Beneficiary of a health insurance.
Exclusion Criteria:
- Patient who is unable to perform a cardio-pulmonary exercise test.
- Cardiac surgery planned during the trial.
- Patient treated by any pulmonary arterial vasodilator drug, as defined in the 2015 PH guidelines (52), within 6 months before inclusion, regardless the duration and the type(s) (oral, intravenous, subcutaneous, inhaled) of administration.
- 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.
- Interventional cardiac catheterization planned during the trial (collateral occlusion, fenestration occlusion, stenting, angioplasty, ablation of rhythm disorder), other than during the screening.
- Participation in another clinical trial or administration of an off-label drug in the 4 weeks preceding the screening.
- Pregnancy, desire for pregnancy, absence of contraception during the study period.
- Severe hepatic insufficiency (Child-Pugh C class).
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.
- Combination with products called "nitric oxide donors" (such as amyl nitrite) or with nitrates in any form, due to the hypotensive effects of nitrates.
- Concomitant administration of PDE5 inhibitors, such as Sildenafil, with guanylate cyclase stimulators, such as Riociguat.
- Combination with the most potent inhibitors of CYP3A4 (eg ketoconazole, itraconazole, ritonavir).
- Disposition to priapism, sclerosis of corpora cavernosa, disease of La Peyronie, sickle cell anemia, multiple myeloma, leukemia.
- 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.
- Severe cardiovascular events, recent (<3 months) or not stabilized: myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage.
- Active hemorrhagic disorders.
- Active gastro-duodenal ulcer.
- Patients with loss of vision of an eye due to non-arteritic anterior ischemic optic neuropathy (NAION), whether or not this event has been associated with previous exposure to a PDE5 inhibitor.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
sildenafil
placebo
• 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