Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH

Last updated: February 20, 2016
Sponsor: University Medical Center Groningen
Overall Status: Completed

Phase

3

Condition

Vascular Diseases

Scleroderma

Diabetes And Hypertension

Treatment

N/A

Clinical Study ID

NCT01726049
Sildenafil Groningen Study
  • Ages > 18
  • All Genders

Study Summary

Aim of the study is to investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure without decrease of cardiac output (CO) and in improvement of exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) with pulmonary hypertension ( PH).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • >18 years

  • Written inform consent

  • PH secondary to diastolic left heart failure defined as

  • PAP mean >25 mmHg

  • Wedge mean >15 mmHg

  • Normal systolic left ventricular (LV) function on echo/nuclear imaging (leftventricular ejection fraction (LVEF) > or =45%)

  • New York Heart Association class (NYHA) II-IV despite heart failure therapy

Exclusion

Exclusion Criteria:

  • Severe noncardiac limitation to exercise (as severe chronic obstructive pulmonarydisease)

  • Other cause of PH besides diastolic heart failure

  • Coronary ischemia or recent myocardial infarction (<6 months)

  • Hypotension ( <90/50 mmHg)

  • Ongoing nitrate therapy

  • Ongoing therapy with citochrome P450 3A4 ( CYP3A4) inhibitors (ketoconazole,erythromycin, cimetidine, clarithromycin, itraconazole, voriconazole and proteaseinhibitors) or CYP3A4 inductors(carbamacepine, phenytoin, phenobarbital, rifampicin,Sint Janskruid ). Furthermore patients will be informed not to drink grapefruit juicewhile on study medication because of the known impact of grape fruit onpharmacokinetics of Sildenafil.

  • Ongoing therapy with alpha -inhibitors

  • Significant mitral or aortic valve dysfunction

  • Severe liver dysfunction

  • Pregnancy

  • Unable to read and comprehend Dutch language

Study Design

Total Participants: 52
Study Start date:
October 01, 2011
Estimated Completion Date:
December 31, 2014

Study Description

Rationale: Treatment of diastolic left heart failure is a challenging task. Compared to systolic left heart failure the level of evidence for known medical treatment regiments is low. Sildenafil, a phosphodiesterase 5 (PDE 5) inhibitor and effective therapy for pulmonary arterial hypertension acts as a selective pulmonary vasodilator by inhibiting the impaired nitric oxide (NO) pathway. Reducing the pulmonary vascular resistance would be the primary target by treatment of diastolic left heart failure with PH. But clinical and hemodynamical studies to evaluate the role of Sildenafil in diastolic heart failure, also called heart failure with preserved ejection fraction (HFpEF) with secondary pulmonary hypertension are lacking. Our hypothesis is that Sildenafil decreases pulmonary artery pressure in patients with HFpEF and pulmonary hypertension.

Objective: To investigate whether Sildenafil treatment results in a hemodynamic improvement and in an improvement of exercise capacity in these patients.

Study design: single-center, prospective, randomized, placebo controlled study. Study population: 52 patients with HFpEF and PH Intervention : One group receives three times daily 20 mg Sildenafil for 2 weeks followed by three times daily 60 mg Sildenafil for 10 weeks. The other group receives three times daily 20 mg of Placebo, followed by 3 times daily 60 mg placebo.

Main study parameters/endpoints:

Primary objectives

  1. To investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure (PAP) in HFpEF patients with PH (investigated invasively by right heart catheterization) .

Secondary objectives

  1. To investigate whether Sildenafil treatment results in an reduction of wedge pressure in HFpEF patients.

  2. To investigate whether Sildenafil treatment results in an improvenemt of cardiac output (CO) in HFpEF patients.

  3. To investigate whether Sildenafil treatment results in improvement of exercise capacity in these patients ( defined as change in VO2max)

Connect with a study center

  • University Medical Center Groningen

    Groningen, 9700 RB
    Netherlands

    Site Not Available

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