Pulmonary Hypertension ``out-of-proportion`` associated to moderate left ventricular dysfunction MedDRA version: 9.1 Level: LLT Classification code 10037406
Conditions
Interventions
Pharmaceutical Form: Tablet
INN or Proposed INN: Tadalafil
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Sponsors
AZIENDA UNIVERSITARIA POLICLINICO UMBERTO I DI ROMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: patients aged > 18 yrs with out-of-proportion hypertension associated to moderate left ventricular dysfunction (a subgroup of the 2? category of the WHO clinical classification system Venice 2003 ervision) NYHA class IIa referred to pulmonary hypertension center for evaluation. - moderate left ventricular dysfunction is defined as left ventricular ejection fraction between 35 and 45% - pulmonary hypertension out-of-proportion associated to left ventricular dysfunction is defined as mean mean pulmonary arterial pressure (PAP = 40-45 mmHg and a transpulmonary pressure gradient (mean PAP- mean pulmonary wedge pressure –PWP) > 12 mmHg (ESC-ERS Guidelines 2009) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria will be idiopatic pulmonary hypertension and pulmonary hypertension secondary to chronic obstructive or restrictive pulmonary disease, recurrent pulmonary embolism, pulmonary venous congestion, acute or chronic inflammatory lung disease, pregnancy or insufficient contraceptive measures, and previous treatment with PDE inhibitors and contraindication to assumption of PDE5i (patients with hepatic or renal insufficiency and known retinal disease) and concomitant use of nitrate. Hypersensitivity to the active substance or to any of the excipients. Acute myocardial infarction within the last 90 days. Severe hypotension (<90/50 mm Hg). Patients who have loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure. Patients with clinically significant aortic and mitral valve disease. Patients with pericardial constriction. Patients with restrictive or congestive cardiomyopathy . Patients with significant left ventricular dysfunction. Patients with life-threatening arrhythmias. Patients with symptomatic coronary artery disease . Patients with uncontrolled hypertension. Pulmonary veno-occlusive disease (PVOD). Patients with severe hepatic cirrhosis (Child-Pugh Class C) have not been studied and therefore dosing. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: TO EVALUATE THE HEMODYNAMIC EFFECT OF 6 MONTHS TADALAFIL ADMINISTRATION ON THE IMPROVEMENT OF PULMONARY VASCULAR RESISTANCE (pvr) ESTIMATION BY RIGHT HEART CATHETERIZATION IN OUT-OF-PROPORTION PULMONARY HYPERTENSION (PH) ASSOCIATED TO MODERATE LEFT VENTRICULAR DYSFUNCTION (A SUB-GROUP OF THE 2? CATEGORY OF THE WHO CLINICAL CLASSIFICATION SYSTEM-VENICE 2003 REVISION);Secondary Objective: - evaluation of the effect of 6 months treatment with tadalafil on the right heart remodelling, measuring the changes in Ventricular Mass (VM), Ventricular Volume (VV), VM/VV ratio, Ejection Fraction (EF), intraventricular asynchrony by MRI; - evaluation of the effect of 6 months treatment with Tadalafil on hemodynamic parameters: Cardiac Index (L/min/m2) and mean right atrial pressure (RAPm), mean pulmonary arterial pressure (PAPm), Pulmonary wedge Pressure (PWP), mean aortic pressure (PAom) by catheterization; - improvement in effort capacity: 6-Minutes Walking Test (6MWT) - to assess the changes in endothelial function parameters: endothelin 1, sCRP, cGMP, atrial and brain natriuretic peptide (ANP - BNP) and cytokines (IL1, IL6, TGF beta, TNF alfa, VEGF, VCAM);Primary end point(s): Primary Objective: to evaluate the hemodynamic effect of 6 months Tadalafil administration on the improvement of Pulmonary Vascular Resistance (PVR) estimation by right heart Catheterization. | — |
Countries
Italy
Outcome results
None listed