Sildenafil for Secondary Pulmonary Hypertension Due to Valvular Disease

Phase 4

Completed

• Conditions: Pulmonary Hypertension; Valvular Heart Disease
• Interventions: Drug: Sildenafil Citrate; Drug: Placebo

• Registration Number: NCT00862043
• Lead Sponsor: Hospital General Universitario Gregorio Marañon

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2009-03-13
• Study First Submitted QC: 2009-03-13
• Study First Posted: 2009-03-16
• Study Start: 2009-04
• Primary Completion: 2016-07
• Study Completion: 2016-07
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-22
• Last Update Posted: 2016-09-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sildenafil Citrate	Sildenafil Citrate	Sildenafil Citrate 40 mg t.i.d. oral
Placebo	Placebo	Sildenafil-matched oral placebo 40 mg t.i.d

Primary Outcome Measures

Name	Time	Method
Combined Outcome End-Point: all-cause mortality or hospital admission for heart failure, worsening of World Health Organization (WHO) functional class, or of the patient global assessment score	Six months

Secondary Outcome Measures

Name	Time	Method
Rate of progression/regression of tricuspid regurgitation by Doppler-echocardiography	3 & 6 Months
Number of hospital admissions caused by or related to heart failure in each patient	6 months
Change from baseline to the sixth month in the in the six-minute walk test	6 Months
All cause mortality	6 Months
Cardiovascular mortality	6 months
Change on right ventricular (RV) dimensions and function assessed by Doppler echocardiography	3 & 6 months
Change on RV volumes and function assessed by cardiac magnetic resonance	6 Months
Change on the right catheterization hemodynamic parameters	6 Months
Identify patients who are more likely to respond to therapy by pharmacogenetics analysis	6 Months
Change on WHO functional capacity	3 & 6 Months

Trial Locations

Locations (18)

Hospital Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Clínico de Valladolid; 🇪🇸 Valladolid, Spain

Hospital Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital Universitario Alava; 🇪🇸 Vitoria, Alava, Spain

Hospital de Leon; 🇪🇸 Leon, Spain

Hospital German Trias y Pujol; 🇪🇸 Badalona, Barcelona, Spain

Hospital Juan Canalejo; 🇪🇸 La Coruna, Spain

Hospital Fundación de Alcorcón; 🇪🇸 Alcorcón, Madrid, Spain

Hospital Universitario Santiago de Compostela; 🇪🇸 Santiago de Compostela, A Coruña, Spain

Hospital Puerta de Hierro; 🇪🇸 Majadahonda, Madrid, Spain

Hospital de la Santa Creu y San Pau; 🇪🇸 Barcelona, Barcelon, Spain

Hospital Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital de Galdakao; 🇪🇸 Galdakao, Vizcaya, Spain

Hospital General Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

Hospital Infanta Leonor; 🇪🇸 Madrid, Spain

Hospital Universitario de Canarias; 🇪🇸 Tenerife, Spain

Hospital Virgen de la Victoria; 🇪🇸 Malaga, Spain