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

September 22, 2016 updated by: Hospital General Universitario Gregorio Marañon

Sildenafil for Improving Outcomes After Valvular Correction

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Córdoba, Spain
        • Hospital Reina Sofía
      • Granada, Spain
        • Hospital Virgen de las Nieves
      • La Coruna, Spain
        • Hospital Juan Canalejo
      • Leon, Spain
        • Hospital de León
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañón
      • Madrid, Spain
        • Hospital 12 de Octubre
      • Madrid, Spain
        • Hospital Infanta Leonor
      • Malaga, Spain
        • Hospital Virgen de la Victoria
      • Salamanca, Spain
        • Hospital Universitario De Salamanca
      • Tenerife, Spain
        • Hospital Universitario de Canarias
      • Valladolid, Spain
        • Hospital Clínico de Valladolid
    • A Coruña
      • Santiago de Compostela, A Coruña, Spain
        • Hospital Universitario Santiago de Compostela
    • Alava
      • Vitoria, Alava, Spain
        • Hospital Universitario Alava
    • Barcelon
      • Barcelona, Barcelon, Spain
        • Hospital de la Santa Creu y San Pau
    • Barcelona
      • Badalona, Barcelona, Spain
        • Hospital German Trias y Pujol
    • Madrid
      • Alcorcón, Madrid, Spain
        • Hospital Fundación de Alcorcón
      • Majadahonda, Madrid, Spain
        • Hospital Puerta de Hierro
    • Vizcaya
      • Galdakao, Vizcaya, Spain
        • Hospital de Galdakao

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sildenafil Citrate
Sildenafil Citrate 40 mg t.i.d. oral
Drug: Sildenafil Citrate
40 mg t.i.d.
Placebo Comparator: Placebo
Sildenafil-matched oral placebo 40 mg t.i.d
Drug: Placebo
Placebo t.i.d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: Six months
Six months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital General Universitario Gregorio Marañon

Collaborators

Instituto de Salud Carlos III
Fundación de Investigación en Red en Enfermedades Cardiovasculares

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

March 13, 2009

First Submitted That Met QC Criteria

March 13, 2009

First Posted (Estimate)

March 16, 2009

Study Record Updates

Last Update Posted (Estimate)

September 23, 2016

Last Update Submitted That Met QC Criteria

September 22, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIBHGM-SIOVAC
  • 2007-007033-40 (EudraCT Number)
  • EC07-90772 (Other Identifier: Agencia Española del Medicamento y Productos Sanitarios)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe