Sildenafil in HFpEF and PH

Pulmonary Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01726049
• Other study ID #: Sildenafil Groningen Study
• Status: Completed
• Phase: Phase 3
• First received: September 21, 2012
• Last updated: February 2, 2015
• Start date: October 2011
• Est. completion date: December 2014

Study information

• Verified date: February 2015
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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 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 CO in HFpEF patients.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

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
Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Pfizer

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	echocardiographic parameters of diastolic LV dysfunction		12 weeks	No
Primary	mean pulmonary artery pressure measured by right heart catheterization		12 weeks	No
Secondary	VO2max		12 weeks	No
Secondary	cardiac output measured invasively by right heart catheterization		12 weeks	No
Secondary	wedge pressure measured invasively by right heart catheterization		12 weeks	No