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Trial record 1 of 1 for:    NCT01726049
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Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH

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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

Tracking Information
First Submitted Date  ICMJE September 21, 2012
First Posted Date  ICMJE November 14, 2012
Results First Submitted Date  ICMJE October 16, 2015
Results First Posted Date  ICMJE March 21, 2016
Last Update Posted Date March 21, 2016
Study Start Date  ICMJE October 2011
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2016)
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
Original Primary Outcome Measures  ICMJE
 (submitted: November 8, 2012)
  • mean pulmonary artery pressure measured by right heart catheterisatien [ Time Frame: 12 weeks ]
  • cardiac output measured invasively by right heart catheterization [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2016)
  • VO2max [ Time Frame: baseline and 12 weeks ]
    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 ]
    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 ]
    Difference in change of wedge pressure between baseline and 12 weeks between Sildenafil group and Placebo group
Original Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2012)
VO2max [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: November 8, 2012)
Echocardiographic Parameters of Diastolic LV Dysfunction [ Time Frame: 12 weeks ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH
Official Title  ICMJE Effects of Sildenafil on Pulmonary Arterial Pressure in Patients With Heart Failure With Preserved Ejection Fraction ( HFpEF) and Pulmonary Hypertension
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Heart Failure, Diastolic
  • Pulmonary Hypertension
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
Study Arms  ICMJE
  • Active Comparator: Sildenafil
    Sildenafil orally 3 times 20mg for 2 weeks , followed by 3 times 60 mg for 10 weeks
    Intervention: Drug: Sildenafil
  • Placebo Comparator: Placebo
    placebo orally 3 times 20mg tablets, followed by 3 times 60 mg for 10 weeks
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 8, 2012)
52
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01726049
Other Study ID Numbers  ICMJE Sildenafil Groningen Study
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party E.S. Hoendermis, University Medical Center Groningen
Study Sponsor  ICMJE University Medical Center Groningen
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: E S Hoendermis, MD PhD University Medical Center Groningen
PRS Account University Medical Center Groningen
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP