Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Sildenafil in HFpEF and PH

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University Medical Centre Groningen
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
E.S. Hoendermis, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01726049
First received: September 21, 2012
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

Aim of the study is to investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure without decrease of CO and in improvement of exercise capacity in HFpEF patients with PH.


Condition Intervention Phase
Heart Failure With Preserved Ejection Fraction
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 Centre Groningen:

Primary Outcome Measures:
  • mean pulmonary artery pressure measured by right heart catheterization [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • cardiac output measured invasively by right heart catheterization [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • VO2max [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • echocardiographic parameters of diastolic LV dysfunction [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: October 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sildenafil 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 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 PDE 5 inhibitor and effective therapy for pulmonary arterial hypertension acts as a selective pulmonary vasodilator by inhibiting the impaired 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 without decrease of CO in HFpEF patients with PH (investigated invasively by right heart catheterization) .

Secondary objectives

  1. To investigate whether Sildenafil treatment results in a reduction of wedge pressure in HFpEF patients.
  2. 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
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 LV function on echo/MUGA (LVEF > 45%)
  • NYHA II-IV despite HF therapy

Exclusion Criteria:

  • Severe noncardiac limitation to exercise (COPD etc)
  • 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 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

Contacts
Contact: E S Hoendermis, MD PhD 0031 50 3616161 E.S.Hoendermis@umcg.nl
Contact: O Bondarenko, MD 0031503616161 o.bondarenko@umcg.nl

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

No publications provided

Responsible Party: E.S. Hoendermis, MD, PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01726049     History of Changes
Other Study ID Numbers: Sildenafil Groningen Study
Study First Received: September 21, 2012
Last Updated: September 5, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
HFpEF
PH

Additional relevant MeSH terms:
Heart Failure
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Sildenafil
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on November 25, 2014