Sildenafil for Secondary Pulmonary Hypertension Due to Valvular Disease (SIOVAC)

Hospital General Universitario Gregorio Marañon

Status and phase

Completed

Phase 4

Conditions

Valvular Heart Disease

Pulmonary Hypertension

Treatments

Drug: Placebo

Drug: Sildenafil Citrate

Study type

Interventional

Funder types

Other

Identifiers

NCT00862043

FIBHGM-SIOVAC

EC07-90772 (Other Identifier)

2007-007033-40 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate the clinical efficacy of the mid-term treatment with sildenafil in patients with persistent moderate or severe pulmonary hypertension (PH) after a heart valve intervention.

Full description

Phase IV, prospective, multicenter, randomized, double-blind, placebo-controlled, academically funded clinical trial, with 6 months follow-up. A total of 354 patients will be recruited. Inclusion criteria are: 1) successful surgical or percutaneous repair of a cardiac valve at least one year before screening and 2) persistent moderate or severe PH, and 3) absence of any residual significant valvular lesion. Patients will be randomized 1:1 to received sildenafil 40 mg t.i.d. or placebo. The primary endpoint is a clinical composite score combining: all-cause mortality, hospital admission for heart failure, World Health Organization (WHO) functional class, and the patient global assessment score. Additional clinical and mechanistic secondary end-points are defined.

Enrollment

200 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age at the date of selection ≥ 18 years
Mean pulmonary pressure ≥ 30 mmHg, measured by a Swan-Ganz catheter placed in the pulmonary artery
Heart valve intervention: surgical or percutaneous replacement, repair or dilatation performed at least one year before inclusion
Stable clinical condition for at least one month, without hospital admissions for heart failure, and on appropriate and stable doses of conventional cardiovascular medications

Exclusion criteria

Requiring or likely to require the following medications: organic nitrates, alpha-blocker therapy, potent cytochrome P450 3A4 inhibitors (erythromycin, ketoconazole, cimetidine, HIV protease inhibitors such ritonavir and saquinavir) Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
Patients with resting hypotension, with systolic blood pressure < 90 mmHg
Patients with retinitis pigmentosa
Anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease) or patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia)
Severe renal impairment with creatinine clearance < 30 ml/min
Significant hepatic dysfunction
Prosthesis or valvular dysfunction with hemodynamic repercussion.
Pregnant or breast-feeding women
Patients unlikely to cooperate in the study or with inability or unwillingness to give informed consent
Life expectancy less than 2 years due to non-cardiac disease