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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01726049
Recruitment Status : Completed
First Posted : November 14, 2012
Results First Posted : March 21, 2016
Last Update Posted : March 21, 2016
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
E.S. Hoendermis, University Medical Center Groningen

Study Description
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Brief 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).

Condition or disease Intervention/treatment Phase
Heart Failure, Diastolic Pulmonary Hypertension Drug: Sildenafil Drug: Placebo Phase 3

Detailed 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)
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Sildenafil on Pulmonary Arterial Pressure in Patients With Heart Failure With Preserved Ejection Fraction ( HFpEF) and Pulmonary Hypertension
Study Start Date : October 2011
Actual Primary Completion Date : September 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Sildenafil
Sildenafil orally 3 times 20mg for 2 weeks , followed by 3 times 60 mg for 10 weeks
 Drug: Sildenafil
Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks
Placebo Comparator: Placebo
placebo orally 3 times 20mg tablets, followed by 3 times 60 mg for 10 weeks
 Drug: Placebo
Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks


Outcome Measures
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Primary Outcome Measures :
  1. Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization [ Time Frame: baseline and 12 weeks ]
    change of mean pulmonary artery pressure between baseline and 12 weeks measured by heart catheterisation


Secondary Outcome Measures :
  1. VO2max [ Time Frame: baseline and 12 weeks ]
    difference in change of VO2 max between baseline and 12 weeks between Sildenafil and placebo group

  2. Cardiac Output Measured Invasively by Right Heart Catheterization [ Time Frame: baseline and 12 weeks ]
    difference in change of cardiac output between baseline and 12 weeks between Sildenafil and Placebo group

  3. Wedge Pressure Measured Invasively by Right Heart Catheterization [ Time Frame: baseline and 12 weeks ]
    Difference in change of wedge pressure between baseline and 12 weeks between Sildenafil group and Placebo group


Other Outcome Measures:
  1. Echocardiographic Parameters of Diastolic LV Dysfunction [ Time Frame: 12 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (left ventricular ejection fraction (LVEF) > or =45%)
  • New York Heart Association class (NYHA) II-IV despite heart failure therapy

Exclusion Criteria:

  • Severe noncardiac limitation to exercise (as severe chronic obstructive pulmonary disease)
  • 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 protease inhibitors) or CYP3A4 inductors(carbamacepine, phenytoin, phenobarbital, rifampicin, Sint Janskruid ). Furthermore patients will be informed not to drink grapefruit juice while on study medication because of the known impact of grape fruit on pharmacokinetics of Sildenafil.
  • Ongoing therapy with alpha -inhibitors
  • Significant mitral or aortic valve dysfunction
  • Severe liver dysfunction
  • Pregnancy
  • Unable to read and comprehend Dutch language
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01726049


Locations
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Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700 RB
Sponsors and Collaborators
University Medical Center Groningen
Pfizer
Investigators
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Principal Investigator: E S Hoendermis, MD PhD University Medical Center Groningen
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: E.S. Hoendermis, MD, PhD, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT01726049    
Other Study ID Numbers: Sildenafil Groningen Study
First Posted: November 14, 2012    Key Record Dates
Results First Posted: March 21, 2016
Last Update Posted: March 21, 2016
Last Verified: February 2016
Keywords provided by E.S. Hoendermis, University Medical Center Groningen:
HFpEF
PH
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Hypertension
Heart Failure
Heart Failure, Diastolic
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Lung Diseases
 Respiratory Tract Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents