Clinical investigation into efficacy, hemodynamics and tolerability of simvastatin vs placebo in patients with pulmonary arterial hypertension(Shorttitle: SIPHT)Double-blind, randomized, prospective Phase III-b study for 6 months with adjusting doses of simvastatin (40/80 mg daily) or placebo followed by an open-label period with a final dose of simvastatin 80 mg daily for another 6 months - SIPHT

• Conditions: Modified NYHA class II or III patients with Pulmonary Hypertension (PH), ICD: 416.9; MedDRA version: 8.1Level: LLTClassification code 10020787Term: Hypertension pulmonary

• Registration Number: EUCTR2005-004863-41-DE
• Lead Sponsor: Dept. of Internal Medicine II, University Hospital Giessen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-07-25
• Last Update Posted: 4 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

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 of the trial and appropriate contraception throughout the study for women with child-bearing potential

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

1.Pregnancy and/or lactation
2.PH of any cause other than permitted in the entry criteria
3.Contraindication for CMR scan or heart catheterization
4.Any change in disease-targeted therapy within the last 4 weeks
5.Patients requiring prostanoid therapy at the start of the study
6.Patients already taking a statin
7.Any subject who had received any investigational medication within 1 month prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study
8.Known intolerance to HMG-CoA-inhibitors (statins) or any of the excipients
9.Active liver disease, porphyria or elevations of serums transaminases >3 x ULN (upper limit of normal) or bilirubin > 1.5 x ULN
10.Concomitant administration of potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone), ciclosporin and danazole.
11.History or suspicion of inability to cooperate adequately
12. Severe renal insufficiency (serum creatinine level 4.0 mg/dL [354 µmol/L])

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess efficacy on pulmonary artery pressure after six months of therapy;Secondary Objective: To assess clinical, hemodynamic, respiratory, functional and cardiovascular parameters following once daily multiple oral doses of simvastatin for 12 months.<br><br>To assess efficacy and tolerability of simvastatin in the treatment of patients with PH compared to placebo for six months.<br><br>To assess tolerability of long term once daily multiple oral doses of simvastatin and placebo in PH<br>;Primary end point(s): Pulmonary artery pressure after 6 months of treatment compared to baseline (Day 2)