Sildenafil for Secondary Pulmonary Hypertension Due to Valvular Disease

Pulmonary Hypertension Clinical Trial

— SIOVAC  

Official title:

Sildenafil for Improving Outcomes After Valvular Correction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00862043
• Other study ID #: FIBHGM-SIOVAC
• Secondary ID: 2007-007033-40EC
• Status: Completed
• Phase: Phase 4
• First received: March 13, 2009
• Last updated: September 22, 2016
• Start date: April 2009
• Est. completion date: July 2016

Study information

• Verified date: September 2016
• Source: Hospital General Universitario Gregorio Marañon
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of MedicinesSpain: Ministry of HealthSpain: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Diseases
• Heart Valve Diseases
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension
• Valvular Heart Disease

Intervention

Drug:
• Sildenafil Citrate
40 mg t.i.d.
• Placebo
Placebo t.i.d.

Locations

Country	Name	City	State
Spain	Hospital Fundación de Alcorcón	Alcorcón	Madrid
Spain	Hospital German Trias y Pujol	Badalona	Barcelona
Spain	Hospital de la Santa Creu y San Pau	Barcelona	Barcelon
Spain	Hospital Reina Sofía	Córdoba
Spain	Hospital de Galdakao	Galdakao	Vizcaya
Spain	Hospital Virgen de las Nieves	Granada
Spain	Hospital Juan Canalejo	La Coruna
Spain	Hospital de Leon	Leon
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Infanta Leonor	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Santiago de Compostela	Santiago de Compostela	A Coruña
Spain	Hospital Universitario de Canarias	Tenerife
Spain	Hospital Clínico de Valladolid	Valladolid
Spain	Hospital Universitario Alava	Vitoria	Alava

Sponsors (3)

Lead Sponsor	Collaborator
Hospital General Universitario Gregorio Marañon	Fundación de Investigación en Red en Enfermedades Cardiovasculares, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change from baseline to the sixth month in the in the six-minute walk test		6 Months	No
Secondary	Change on WHO functional capacity		3 & 6 Months	No
Secondary	All cause mortality		6 Months	Yes
Secondary	Cardiovascular mortality		6 months	Yes
Secondary	Number of hospital admissions caused by or related to heart failure in each patient		6 months	No
Secondary	Rate of progression/regression of tricuspid regurgitation by Doppler-echocardiography		3 & 6 Months	No
Secondary	Change on right ventricular (RV) dimensions and function assessed by Doppler echocardiography		3 & 6 months	No
Secondary	Change on RV volumes and function assessed by cardiac magnetic resonance		6 Months	No
Secondary	Change on the right catheterization hemodynamic parameters		6 Months	No
Secondary	Identify patients who are more likely to respond to therapy by pharmacogenetics analysis		6 Months	No

External Links

•   Cardiovascular Research Spanish National Network
•   Funding Agent
•   Funding Agent