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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
E.S. Hoendermis, University Medical Center Groningen
ClinicalTrials.gov Identifier:
NCT01726049
First received: September 21, 2012
Last updated: February 20, 2016
Last verified: February 2016
  Purpose
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 Intervention Phase
Heart Failure, Diastolic
Pulmonary Hypertension
Drug: Sildenafil
Drug: Placebo
Phase 3

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: Effects of Sildenafil on Pulmonary Arterial Pressure in Patients With Heart Failure With Preserved Ejection Fraction ( HFpEF) and Pulmonary Hypertension

Resource links provided by NLM:


Further study details as provided by University Medical Center Groningen:

Primary Outcome Measures:
  • Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    change of mean pulmonary artery pressure between baseline and 12 weeks measured by heart catheterisation


Secondary Outcome Measures:
  • VO2max [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    difference in change of VO2 max between baseline and 12 weeks between Sildenafil and placebo group

  • Cardiac Output Measured Invasively by Right Heart Catheterization [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    difference in change of cardiac output between baseline and 12 weeks between Sildenafil and Placebo group

  • Wedge Pressure Measured Invasively by Right Heart Catheterization [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Difference in change of wedge pressure between baseline and 12 weeks between Sildenafil group and Placebo group


Other Outcome Measures:
  • Echocardiographic Parameters of Diastolic LV Dysfunction [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 52
Study Start Date: October 2011
Study Completion Date: December 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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)
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
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: NCT01726049

Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700 RB
Sponsors and Collaborators
University Medical Center Groningen
Pfizer
Investigators
Principal Investigator: E S Hoendermis, MD PhD University Medical Center Groningen
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: E.S. Hoendermis, MD, PhD, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT01726049     History of Changes
Other Study ID Numbers: Sildenafil Groningen Study 
Study First Received: September 21, 2012
Results First Received: October 16, 2015
Last Updated: February 20, 2016
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Center Groningen:
HFpEF
PH

Additional relevant MeSH terms:
Hypertension
Heart Failure
Hypertension, Pulmonary
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

ClinicalTrials.gov processed this record on September 28, 2016