Clinical investigation into efficacy, hemodynamics and tolerability of simvastatin vs placebo in patients with pulmonary arterial hypertension

INTERVENTION: Trade Name: simvastatin 40 mg tablets Product Name: simvastatin Pharmaceutical Form: Capsule* Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Product Name: simvastatin 40 mg Product Code: simvastatin 40 mg Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: simvastatin CAS Number: 79902‐63‐9 Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 40‐40 CONDITION: Modified NYHA class II or III patients with Pulmonary Hypertension (PH), ICD: 416.9 ; MedDRA version: 8.1 Level: LLT Classification code 10020787 Term: Hypertension pulmonary PRIMARY OUTCOME: Main Objective: To assess efficacy on pulmonary artery pressure after six months of therapy Primary end point(s): Pulmonary artery pressure after 6 months of treatment compared to baseline (Day 2) Secondary Objective: To assess clinical, hemodynamic, respiratory, functional and cardiovascular parameters following once daily multiple oral doses of simvastatin for 12 months.; ; To assess efficacy and tolerability of simvastatin in the treatment of patients with PH compared to placebo for six months.; ; To assess tolerability of long term once daily multiple oral doses of simvastatin and placebo in PH; INCLUSION CRITERIA: 1. Female and male patients of any racial origin with PH 2. Having fulfilled his/her 18th birthday on Day 1 of the study 3. Modified NYHA functional class II or III 4. PH due to idiopathic pulmonary arterial hypertension or collagen vascular disease associated PH 5. Cardiac catheterization within the last year consistent with PH, specifically PAPm greater equal 25 mmHg (at rest), pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) smaller equal 15 mmHg, and PVR >3 mmHg/L/min 6. Echocardiogram on Day 1 consistent with PH, specifically evidence of right ventricular hypertrophy or dilation, evidence of normal left ventricular function, and absence of mitral valve stenosis 7. Six‐minute walk test between 150 and 450 m 8. Patients receiving conventional PH therapy. Stable for one month. 9. Able to understand and willing to sign the Informed Consent Form. 10. Negative pregnancy test (ß‐HCG) at the start