Sildenafil for Secondary Pulmonary Hypertension Due to Valvular Disease

Overview

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.

Full Title of Study: “Sildenafil for Improving Outcomes After Valvular Correction”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 2016

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.

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Sildenafil Citrate
    • Sildenafil Citrate 40 mg t.i.d. oral
  • Placebo Comparator: Placebo
    • Sildenafil-matched oral placebo 40 mg t.i.d

Clinical Trial Outcome Measures

Primary 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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Hospital General Universitario Gregorio Marañon
  • Collaborator
    • Instituto de Salud Carlos III
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Javier Bermejo, MD, PhD, Principal Investigator, Hospital General Universitario Gregorio Maranon

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