Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction

NCT03037580 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: TDE-HF-301
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 82

Brief Summary

This was a multicenter, randomized (1:1; oral treprostinil to placebo), double-blind, placebo-controlled study in subjects with World Health Organization (WHO) Group 2 pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF). Once randomized, subjects took the initial dose of study drug at the study site on the day of randomization. Subjects returned to the study site for visits scheduled at Weeks 6, 12, 18, and 24. The duration of study participation was approximately 28 weeks from Screening until study completion (includes a 30-day Screening Phase and 24-week Treatment Phase). The study was discontinued by the Sponsor on 14 October 2019 due to slow enrollment. As only a small portion of the anticipated total subjects had been enrolled, with many terminating early due to the study termination, there was a limited ability to explore the effect of oral treprostinil in this indication in this study.

Conditions

Pulmonary Hypertension; Heart Failure With Preserved Ejection Fraction

Keywords

Pulmonary Hypertension; 6-Minute Walk Test; HFpEF; Oral Treprostinil

Outcome Measures

Primary Outcomes (1)

• Change in 6MWD From Baseline to Week 24

  The intent of the 6-Minute Walk Test (6MWT) is to evaluate exercise capacity associated with carrying out activities of daily living.

  Baseline to Week 24

Secondary Outcomes (3)

• Change in NT-proBNP Levels From Baseline to Week 24

  Baseline to Week 24

• Number of Subjects With First Clinical Worsening Event From Baseline to Week 24

  Baseline to Week 24

• Change in WHO FC From Baseline to Week 24

  Baseline to Week 24

Study Arms (2)

Oral treprostinil

EXPERIMENTAL

Sustained-release oral tablets for TID administration

Drug: Oral treprostinil

Placebo

PLACEBO COMPARATOR

Placebo (sugar pill) for TID oral administration

Drug: Placebo

Interventions

Oral treprostinil DRUG

Sustained-release oral tablets for TID administration

Also known as: Treprostinil diethanolamine, treprostinil diolamine

Oral treprostinil

Placebo DRUG

Placebo (sugar pill) for TID oral administration

Also known as: Matching placebo (sugar pill)

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject voluntarily gave informed consent to participate in the study.
• The subject was 18 to 85 years of age (inclusive) at Screening (ie, date of providing written informed consent).
• A subject could qualify if they had undergone a right heart catheterization (RHC) within 180 days of Baseline.
• The subject had a diagnosis of heart failure with a left ventricular ejection fraction (LVEF) ≥45% by ECHO completed during Screening (prior to randomization).
• The subject's baseline 6MWD was at least 150 meters.
• The subject had pulmonary function tests conducted within 6 months of Screening or during the Screening Phase.
• Subjects on a chronic medication for heart failure were on a stable dose for ≥30 days prior to randomization.
• In the opinion of the Investigator, the subject was able to communicate effectively with study personnel, and was considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.
• Women of childbearing potential, including any female who had experienced menarche and who had not undergone successful surgical sterilization or was not postmenopausal, must have practiced true abstinence from intercourse when it was in line with their preferred and usual lifestyle, or have used 2 different forms of highly effective contraception for the duration of the study, and for at least 30 days after discontinuing study drug. Male subjects with a partner of childbearing potential must have used a condom during the length of the study, and for at least 48 hours after discontinuing study drug.
• Subjects on chronic medications (eg, inhaled corticosteroids, long-acting beta2 adrenergic agonist, long acting muscarinic antagonists, combination inhaled drugs, anti-inflammatory drugs, oral/parenteral corticosteroids, or biologic agents) for any underlying respiratory condition were on a stable dose for ≥30 days prior to randomization.

You may not qualify if:

• The subject was pregnant or lactating.
• In the opinion of the Principal Investigator, the subject had a primary diagnosis of PH other than WHO Group 2 PH.
• The subject had shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation of therapy or inability to effectively titrate that therapy.
• The subject had been hospitalized for a cardiopulmonary indication within 30 days of randomization.
• The subject had a myocardial infarction within 90 days of randomization.
• The subject had cardiac resynchronization therapy within 90 days of randomization or anticipated resynchronization therapy during the study treatment period.
• The subject had liver function tests greater than 3 times the upper limit of normal at Screening, clinically significant liver disease/dysfunction, known Child-Pugh Class C hepatic disease, or noncirrhotic portal hypertension.
• The subject had uncontrolled systemic hypertension, systolic blood pressure \<100 mmHg, or a resting heart rate \>100 beats per minute at Baseline.
• The subject had known genetic hypertrophic cardiomyopathy, sarcoidosis, or cardiac amyloidosis.
• The subject had a known history of any LVEF less than 40% by ECHO within 3 years of randomization. Note: a transient decline in LVEF below 40% that occurred and recovered more than 6 months before the start of Screening and was associated with an acute intercurrent condition (eg, atrial fibrillation) was allowed.
• The subject had hemodynamically significant valvular heart disease as determined by the Investigator, including: greater than mild aortic and/or mitral stenosis or severe mitral and/or aortic regurgitation (\>Grade 3)
• The subject had a Body Mass Index \>45 kg/m\^2.
• The subject had any musculoskeletal disorder, or had any other condition that limited ambulation.
• The subject had end-stage renal disease requiring/receiving dialysis.
• The subject participated in an investigational drug or device study within 30 days prior to the first dose of study drug.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (82)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Banner University Medical Center Phoenix

Phoenix, Arizona, 85006, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

VA Healthcare System of Greater Los Angeles

Los Angeles, California, 90073, United States

Location

University of California Los Angeles Pulmonary Division

Los Angeles, California, 90095, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90211, United States

Location

University of California - Davis Medical Center

Sacramento, California, 95817, United States

Location

Santa Barbara Cottage Hospital

Santa Barbara, California, 93105, United States

Location

Aurora Denver Cardiology Associates

Aurora, Colorado, 80012, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

South Denver Cardiology

Littleton, Colorado, 80120, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Medical Faculty Associates, George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Bay Area Cardiology Associates

Brandon, Florida, 33511, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

St. Vincent's Lung, Sleep, and Critical Care Specialists

Jacksonville, Florida, 33204, United States

Location

Central Florida Pulmonary Group, P.A.

Orlando, Florida, 32803, United States

Location

Florida Hospital

Orlando, Florida, 32806, United States

Location

University of South Florida; Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Cleveland Clinic of Florida

Weston, Florida, 33331, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Piedmont Physicians Georgia Lung

Austell, Georgia, 30309, United States

Location

WellStar Medical Group

Marietta, Georgia, 30060, United States

Location

University of Illinois at Chicago Hospital

Chicago, Illinois, 60612, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

OSF HealthCare

Peoria, Illinois, 61614, United States

Location

Indiana University Health Methodist Research Institute, INC

Indianapolis, Indiana, 46202, United States

Location

Community Physician Network, Heart and Vascular Care

Indianapolis, Indiana, 46250, United States

Location

Saint Vincent Hospital and Health Services

Indianapolis, Indiana, 46260, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 55242, United States

Location

Iowa Heart Center

West Des Moines, Iowa, 50266, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40202, United States

Location

University of Louisville Physicians Outpatient Center

Louisville, Kentucky, 40202, United States

Location

Chest Medicine Associates

South Portland, Maine, 04106, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

St. Elizabeth's Medical Center

Brighton, Massachusetts, 02135, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Spectrum Health Medical Group

Grand Rapids, Michigan, 49503, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

St. Luke's Hospital

Chesterfield, Missouri, 63017, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Barnabas Health Lung Center

Newark, New Jersey, 07112, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Pulmonary Health Physicians, PC

Syracuse, New York, 13066, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Asheville Cardiology Associates

Asheville, North Carolina, 28803, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Pinehurst Medical Clinic

Pinehurst, North Carolina, 28374, United States

Location

The Lindner Research Center The Christ Hospital Health Network

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

The Oregon Clinic

Portland, Oregon, 97225, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17601, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

AnMed Health Pulmonary and Sleep Medicine

Anderson, South Carolina, 29621, United States

Location

VitaLink Research - Anderson

Anderson, South Carolina, 29621, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Stern Cardiovascular Foundation

Germantown, Tennessee, 38138, United States

Location

Summit Medical Group

Knoxville, Tennessee, 37909, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Texas Tech University Health Sciences Center

Lubbock, Texas, 79905, United States

Location

Intermountain Medical Center

Murray, Utah, 84157-7000, United States

Location

Inova Heart and Vascular Institute

Falls Church, Virginia, 22042, United States

Location

Sentara Cardiovascular Research Institute

Norfolk, Virginia, 23507, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Carilion Clinic

Roanoke, Virginia, 24014, United States

Location

Providence Medical Research Center

Spokane, Washington, 99204, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

treprostinil; Sugars

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Carbohydrates

Results Point of Contact

• Title: Louis Holdstock
• Organization: United Therapeutics

lholdstock@unither.com

919-425-8866

Study Officials

• Mardi Gomberg-Maitland, MD

  George Washington University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2017
• First Posted: January 31, 2017
• Study Start: August 15, 2017
• Primary Completion: December 3, 2019
• Study Completion: December 3, 2019
• Last Updated: November 10, 2020
• Results First Posted: October 22, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (82)