Sildenafil in Heart Failure With Reactive Pulmonary Hypertension (Sildenafil-HF)

The purpose of this study is to determine whether Sildenafil 20mg taken three times a day is effective in the treatment of Heart Failure with Reactive Pulmonary Hypertension. This is a double-blind, placebo controlled trial.

Study Overview

• Status: Terminated
• Conditions: Heart Failure With Reactive Pulmonary Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Sildenafil

Detailed Description

Patients will be screened at the time of a diagnositic Right Heart Catheterization. Patients will be selected based on pressures measured during this procedure, current medications, and current symptoms. At baseline a 6 minute walk test and quality of life questionnaire will be administered. Medical records will be reviewed and results of recent testing will be recorded. Qualifying participants will be randomized to receive 90 days of either placebo or sildenafil 20 mg three times a day. Randomized patients will be followed for safety and efficacy by phone and as otherwise clinically indicated.

At the end of the 90 day treatment period, patients will be evaluated via 6 minute walk, quality of life questionnaire, and other diagnostic tests as clinically indicated. Primary outcome will be change in the 6 minute walk distance. Secondary outcomes will be based on clinically available results such as change in heart pressures measured by right heart catheterization and echocardiogram.

At the end of the treatment period, providers and patients will be unblinded in order to optimize further treatment.

To achieve statistical significance, 64 patients will be enrolled and randomized.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Known chronic heart failure appropriately treated with Angiotensin converting enzyme (ACE) inhibitors and beta blockers, unless contraindicated or poorly tolerated
• indication for right heart catheterization
• pulmonary artery mean pressure >25 mmHg
• pulmonary capillary wedge pressure > 15 mmHg
• pulmonary vascular resistance > 3 Wood units

Exclusion Criteria:

• hypersensitivity, allergy, or intolerable side effect to sildenafil
• history of primary pulmonary hypertension, connective tissue disorder, severe chronic obstructive pulmonary disorder (COPD), pulmonary embolism, or left to right shunt

• co-morbidities, limited exercise intolerance:

  • morbid obesity (BMI >40)
  • COPD with oxygen dependence
  • severe peripheral vascular disease with intermittent claudication
  • status post amputation of lower extremity at any level
  • severe degenerative joint disease preventing normal walking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo three times per day, orally	Drug: Placebo; One capsule three times daily by mouth for 90 days
Active Comparator: Sildenafil; Sildenafil 20 mg three times per day, orally	Drug: Sildenafil; 20 mg three times daily by mouth for 90 days; Other Names: Viagra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Exercise Tolerance	In a controlled laboratory environment, participants will be asked to walk on a treadmill as fast as they can for 6 minutes. The test will be conducted at baseline and after 90 days of treatment. Data will be presented as the change in distance (in feet) walked in 6 minutes between baseline and treatment.	Baseline and 90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Right Ventricular Function	Right ventricular function will be measured using tricuspid annular plane systolic excursion via two dimensional apical four-chamber echocardiography. Data will be collected at baseline and after 90 days of treatment	Baseline and 90 day
Change in Cardiac Output Relative to Body Surface Area (Cardiac Index)	cardiac output will be calculated by multiplying stroke volume by heart rate. Cardiac index will be calculated by dividing cardiac output (Liters/minute) by body surface area (meters squared). Data will be collected at baseline and the end of treatment (90 days)	Baseline and 90 days
Change in Pulmonary Vascular Resistance	Pulmonary vascular resistance will be determined by right heart catheterization. Data will be collected at baseline and at the end of treatment (90 days)	Baseline and 90 days
Change in Blood Pressure	through standard cuff method, participants will have blood pressure measured to determine systolic and diastolic blood pressure as well as mean arterial pressure. data will be collected at baseline and 90 days.	Baseline and 90 days

Collaborators and Investigators

• Sponsor: Maya Guglin
• Investigators: Principal Investigator: Maya E Guglin, MD, PhD, University of Kentucky

Publications and helpful links

General Publications

• Guglin M, Rajagopalan N, Anaya P, Charnigo R. Sildenafil in heart failure with reactive pulmonary hypertension (Sildenafil HF) clinical trial (rationale and design). Pulm Circ. 2016 Jun;6(2):161-7. doi: 10.1086/685548.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: November 26, 2014
• First Submitted That Met QC Criteria: December 1, 2014
• First Posted (Estimate): December 2, 2014

Study Record Updates

• Last Update Posted (Actual): November 7, 2019
• Last Update Submitted That Met QC Criteria: October 23, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Heart Failure; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 14-0628-F3R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No