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

This study has been completed.
Sponsor:
Collaborators:
Instituto de Salud Carlos III
Fundación de Investigación en Red en Enfermedades Cardiovasculares
Information provided by (Responsible Party):
Hospital General Universitario Gregorio Marañon
ClinicalTrials.gov Identifier:
NCT00862043
First received: March 13, 2009
Last updated: September 22, 2016
Last verified: September 2016
  Purpose
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 ]

Enrollment: 200
Study Start Date: April 2009
Study Completion Date: July 2016
Primary Completion Date: July 2016 (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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT00862043

Locations
Spain
Hospital Universitario Santiago de Compostela
Santiago de Compostela, A Coruña, Spain
Hospital Universitario Alava
Vitoria, Alava, Spain
Hospital German Trias y Pujol
Badalona, Barcelona, Spain
Hospital de la Santa Creu y San Pau
Barcelona, Barcelon, Spain
Hospital Fundación de Alcorcón
Alcorcón, Madrid, Spain
Hospital Puerta de Hierro
Majadahonda, Madrid, Spain
Hospital de Galdakao
Galdakao, Vizcaya, Spain
Hospital Reina Sofía
Córdoba, Spain
Hospital Virgen de las Nieves
Granada, Spain
Hospital Juan Canalejo
La Coruna, Spain
Hospital de Leon
Leon, Spain
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
Hospital 12 de Octubre
Madrid, Spain
Hospital Infanta Leonor
Madrid, Spain
Hospital Virgen de la Victoria
Malaga, Spain
Hospital Universitario de Salamanca
Salamanca, Spain
Hospital Universitario de Canarias
Tenerife, Spain
Hospital Clínico de Valladolid
Valladolid, Spain
Sponsors and Collaborators
Hospital General Universitario Gregorio Marañon
Instituto de Salud Carlos III
Fundación de Investigación en Red en Enfermedades Cardiovasculares
Investigators
Principal Investigator: Javier Bermejo, MD, PhD Hospital General Universitario Gregorio Maranon
  More Information

Additional Information:
Responsible Party: Hospital General Universitario Gregorio Marañon
ClinicalTrials.gov Identifier: NCT00862043     History of Changes
Other Study ID Numbers: FIBHGM-SIOVAC  2007-007033-40  EC07-90772 
Study First Received: March 13, 2009
Last Updated: September 22, 2016
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
Phosphodiesterase-Inhibitors
Sildenafil
Outcomes Research

Additional relevant MeSH terms:
Hypertension
Heart Diseases
Hypertension, Pulmonary
Heart Valve Diseases
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Citric Acid
Sildenafil Citrate
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents

ClinicalTrials.gov processed this record on September 23, 2016