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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Hospital General Universitario Gregorio Marañon
Instituto de Salud Carlos III
Fundación de Investigación en Red en Enfermedades Cardiovasculares
Information provided by (Responsible Party):
Hospital General Universitario Gregorio Marañon Identifier:
First received: March 13, 2009
Last updated: August 18, 2015
Last verified: August 2015
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.

Condition Intervention Phase
Pulmonary Hypertension
Valvular Heart Disease
Drug: Sildenafil Citrate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Sildenafil for Improving Outcomes After Valvular Correction

Resource links provided by NLM:

Further study details as provided by Hospital General Universitario Gregorio Marañon:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

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

Estimated Enrollment: 198
Study Start Date: April 2009
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00862043

Contact: Javier Bermejo, MD, PhD 34 91 5868815
Contact: Raquel Yotti, MD, PhD 34 91 5868279

Hospital Universitario Santiago de Compostela Recruiting
Santiago de Compostela, A Coruña, Spain
Principal Investigator: Jose Ramón González-Juanatey, MD, PhD         
Hospital Universitario Alava Recruiting
Vitoria, Alava, Spain
Principal Investigator: Angel María Alonso, MD, PhD         
Hospital German Trias y Pujol Recruiting
Badalona, Barcelona, Spain
Principal Investigator: Antoni Bayés-Genís, MD, PhD         
Hospital de la Santa Creu y San Pau Recruiting
Barcelona, Barcelon, Spain
Principal Investigator: Xavier Borrás, MD, PhD         
Hospital Fundación de Alcorcón Recruiting
Alcorcón, Madrid, Spain
Principal Investigator: Javier Botas, MD, PhD         
Hospital Puerta de Hierro Recruiting
Majadahonda, Madrid, Spain
Principal Investigator: Javier Segovia, MD, PhD         
Hospital de Galdakao Recruiting
Galdakao, Vizcaya, Spain
Principal Investigator: Eva Laraudogoitia, MD         
Hospital Reina Sofía Recruiting
Córdoba, Spain
Principal Investigator: Jose María Arizón, MD, PhD         
Hospital Virgen de las Nieves Recruiting
Granada, Spain
Principal Investigator: Rocío García-Orta, MD, PhD         
Sub-Investigator: Mercedes González de Molinar, MD         
Hospital Juan Canalejo Recruiting
La Coruna, Spain
Sub-Investigator: Maria G Crespo, MD, PhD         
Principal Investigator: Jose Cuenca, MD, PhD         
Hospital de Leon Recruiting
Leon, Spain
Principal Investigator: Mario Castano, MD         
Sub-Investigator: Armando Perez de Prado, MD         
Hospital Infanta Leonor Not yet recruiting
Madrid, Spain
Principal Investigator: Roberto Muñoz-Aguilera, MD, PhD         
Hospital 12 de Octubre Recruiting
Madrid, Spain
Principal Investigator: Fernando Arribas, MD, PhD         
Sub-Investigator: Pilar Escribano, MD, PhD         
Hospital General Universitario Gregorio Maranon Recruiting
Madrid, Spain, 28007
Principal Investigator: Javier Bermejo, MD, PhD         
Sub-Investigator: Raquel Yotti, MD, PhD         
Hospital Virgen de la Victoria Recruiting
Malaga, Spain
Principal Investigator: Eduardo de Teresa, MD, PhD         
Sub-Investigator: Manuel Jiménez-Navarro, MD, PhD         
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain
Principal Investigator: Jose Maria Gonzalez-Santos, MD, PhD         
Sub-Investigator: Candido Martin-Luengo, MD, PhD         
Hospital Universitario de Canarias Not yet recruiting
Tenerife, Spain
Principal Investigator: Francisco Bosa, MD         
Hospital Clínico de Valladolid Recruiting
Valladolid, Spain
Principal Investigator: Jose A San-Roman, MD, PhD         
Sub-Investigator: Luis de la Fuente, MD, PhD         
Sponsors and Collaborators
Hospital General Universitario Gregorio Marañon
Instituto de Salud Carlos III
Fundación de Investigación en Red en Enfermedades Cardiovasculares
Principal Investigator: Javier Bermejo, MD, PhD Hospital General Universitario Gregorio Maranon
  More Information

Additional Information:
No publications provided

Responsible Party: Hospital General Universitario Gregorio Marañon Identifier: NCT00862043     History of Changes
Other Study ID Numbers: FIBHGM-SIOVAC, 2007-007033-40, EC07-90772
Study First Received: March 13, 2009
Last Updated: August 18, 2015
Health Authority: Spain: Spanish Agency of Medicines
Spain: Ministry of Health
Spain: Ethics Committee

Keywords provided by Hospital General Universitario Gregorio Marañon:
Secondary Pulmonary Hypertension
Valvular Heart Disease
Outcomes Research

Additional relevant MeSH terms:
Heart Valve Diseases
Heart Diseases
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents processed this record on December 01, 2015