Clinical investigation into efficacy, haemodynamics and tolerability of simvastatin versus placebo in patients with pulmonary arterial hypertensio

Completed

Conditions: Pulmonary hypertension
Circulatory System
Other pulmonary heart diseases

Registration Number: ISRCTN27178415

Lead Sponsor: niversity Hospital Giessen (Germany)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 40

Inclusion Criteria

1. Female and male patients of any racial origin with pulmonary hypertension (PH)
2. Having fulfilled his/her 18th birthday on day 1 of the study
3. Modified New York Heart Association (NYHA) class II or III
4. PH due to idiopathic pulmonary arterial hypertension or collagen vascular disease associated PH
5. Cardiac catheterisation within the last year consistent with PH, specifically pulmonary artery mean pressure (PAPM) greater than or equal to 25 mmHg (at rest), pulmonary capillary wedge pressure (PCWP) (or left ventricular [LV] end diastolic pressure) less than or equal to 15 mmHg, and peripheral vascular resistance (PVR) greater than 3 mmHg/l/min
6. Echocardiogram on day 1 consistent with PH, more 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-human chorionic gonadotropin [HCG]) at the start of the trial and appropriate contraception throughout the study for women of child-bearing potential

Exclusion Criteria

1. Pregnancy and/or lactation
2. PH of any cause other than permitted in the entry criteria
3. Contraindication for cardiac magnetic resonance (CMR) scan or heart catheterisation
4. Any change in disease-targeted therapy within the last four weeks
5. Patients requiring prostanoid therapy at the start of the study
6. Patients already taking a statin
7. Any subject who has 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 hydroxy-methylglutaryl coenzyme A (HMG-CoA)-inhibitors (statins) or any of the excipients
9. Active liver disease, porphyria or elevations of serums transaminases greater than three times upper limit of normal (ULN) or bilirubin greater than 1.5 x ULN
10. Concomitant administration of potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, human immunodeficiency virus [HIV] protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone, ciclosporin and danazole)
11. History or suspicion of inability to cooperate adequately

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Pulmonary arterial pressure

Secondary Outcome Measures

Name	Time	Method
1. Pulmonary vascular resistance<br>2. Cardiac output<br>3. Right ventricle mass<br>4. Six-minute walk test<br>5. Left ventricular (LV) systolic eccentricity index<br>6. Tei index<br>7. Right atrial area<br>8. Levels of brain natriuretic peptide (BNP) and inflammatory markers<br>9. Urinary iPF2alpha-III levels<br>10. Adverse events<br>11. Concomitant medication