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

ISRCTN ISRCTN27178415
DOI https://doi.org/10.1186/ISRCTN27178415
ClinicalTrials.gov (NCT) NCT00180713
Clinical Trials Information System (CTIS) 2005-004863-41
Protocol serial number SIPHT-001; EudraCT number: 2005-004863-41
Sponsor University Hospital Giessen (Germany)
Funder University Hospital Giessen (Germany)
Submission date
13/05/2006
Registration date
14/06/2006
Last edited
02/02/2010
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Hanna Mach
Scientific

c/o Dr Riethmüller M/R/S
Mittelweg 27
Frankfurt
60318
Germany

Study information

Primary study designInterventional
Study designDouble-blind, randomised, prospective, placebo-controlled (first phase, 6 months), open-label (second phase, 6 months) trial
Secondary study designRandomised controlled trial
Scientific title
Study acronymSiPHT
Study objectivesSimvastatin is significantly effective in lowering the mean pulmonary arterial pressure versus placebo after six months of therapy.
Ethics approval(s)Ethics approval received from the Justus-Liebig-Universität Giessen Ethikkommittee des FB Medizin on the 30th August 2006 (ref: 85/06).
Health condition(s) or problem(s) studiedPulmonary hypertension
InterventionPlease note that as of 02/05/2008 the anticipated start date was updated. The previous anticipated start date was 01/08/2006.

Interventions:
Effects of simvastatin or placebo on haemodynamics (cardiac catheterisation), electrocardiogram (ECG), echocardiogram, cardiac magnetic resonance, lung function test etc.
Intervention typeDrug
PhaseNot Specified
Drug / device / biological / vaccine name(s)Simvastatin
Primary outcome measure(s)

Pulmonary arterial pressure

Key secondary outcome measure(s)

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

Completion date31/07/2008

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration40
Key inclusion criteria1. 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 (β-human chorionic gonadotropin [HCG]) at the start of the trial and appropriate contraception throughout the study for women of child-bearing potential
Key exclusion criteria1. 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
Date of first enrolment16/07/2007
Date of final enrolment31/07/2008

Locations

Countries of recruitment

  • Germany

Study participating centre

c/o Dr Riethmüller M/R/S
Frankfurt
60318
Germany

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 15/05/2010 Yes No
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