adult and adolescent patients with univentricular heart diseases and pulmonary arterial pressure
Conditions
Interventions
Product Name: Mysildecard
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Sponsors
University Hospital of Montpellier
Eligibility
Sex/Gender
All
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the tolerance to effort and the adaptation of pulmonary perfusion by measuring the VE/VCO2 slope in a CPET before and after a 6-month treatment period, between the sildenafil group and the placebo group, among adolescents and adult SV patients with pulmonary hypertension.;Secondary Objective: Comparison before and after a 6-month treatment period, between the Sildenafil group and the placebo group for: 1. The evolution of the clinical, biological and functional status, the health-related quality of life, the function of the univentricular heart in non-invasive imaging and the degree of pulmonary hypertension in cardiac catheterization 2. The compliance and the tolerance of the drug ;Primary end point(s): - The evolution of the VE/VCO2 slope (ventilation per minute / volume of carbon dioxide released slope) measured with CPET before and after the 6 month-treatment period;Timepoint(s) of evaluation of this end point: after the 6-months treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Evolution between inclusion and end of treatment (6 months) for the following criteria: - Clinical endpoints: o Functional class from I to IV (New York Heart Association Functional classification). o Oxygen saturation (SaO2): measured routinely using a transcutaneous sensor in all cyanogen CHD and/or patient with PAH [30]. o 6-minute walk test (6MWT). - Health-related quality of life: o The SF-36 questionnaire [33]. - SV function evaluation with non-invasive imaging: o Echocardiography: systemic blood flow, SV systolic ejection fraction, 2D Strain SV function. o MRI: systemic and pulmonary blood flows in phase contrast, SV systolic ejection fraction and volumes [34]. - NT Pro BNP: this blood test is a biomarker routinely checked in heart failure. It is also a prognostic factor in PAH [35]. - Cardio-pulmonary exercise test (CPET): The CPET has become the "gold standard" exam in the follow-up of heart failure [25] even in CHD patients [30]. The following values will be measured as detailed in our previous studies [3, 36]: o The maximum oxygen consumption (VO2max), o The first anaerobic threshold (AT), the ventilatory anaerobic threshold (AT) using Beaver’s method [37], o The oxygen pulse (ratio VO2/heart rate) at rest, at AT and at the peak, o The OUES (oxygen uptake efficiency slope); VO2 = OUES x log10 VE + b) [38]–[40]. - Lung function: o Spirometry: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio (FEV1%), DEMM25/75, o Capillary lung volume: pulmonary CO/NO transfer (patient seated and lying down) [42,43]. - Cardiac catheterization: mean pulmonary arterial pressure (mmHg). - Percentage of patients compliant at 6 months of study treatment. ;Timepoint(s) of evaluation of this end point: 6 months | — |
Countries
France
Contacts
Public ContactGuillemette TACONNET DECKER
University Hospital of Montpellier
Outcome results
None listed