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Pulmonary HypertensionPhase 3NCT03037580

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

A Phase 3 study testing Oral treprostinil in people with Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction, run by United Therapeutics at 82 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Oral treprostinil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
84 participants
Where
82 sitesUnited States
Study dates
15 Aug 2017to 3 Dec 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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 received any approved pulmonary arterial hypertension (PAH) therapies within 30 days of randomization. Chronic use of an approved phosphodiesterase type 5 inhibitor (PDE5-I) was allowed as long as the subject has been on a stable dose for at least 90 days prior to randomization and had a RHC confirming the parameters necessary for inclusion in the study after being on a stable PDE5-I dose for at least 30 days.
  • 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.
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  • 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.

Trial locations and contacts

82 sites in 1 country.

82 sites in 1 country

United States82 sites

  • Albany Medical College

    Albany, New York, 12208

  • AnMed Health Pulmonary and Sleep Medicine

    Anderson, South Carolina, 29621

  • VitaLink Research - Anderson

    Anderson, South Carolina, 29621

  • Asheville Cardiology Associates

    Asheville, North Carolina, 28803

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Augusta University

    Augusta, Georgia, 30912

  • Aurora Denver Cardiology Associates

    Aurora, Colorado, 80012

  • University of Colorado Denver

    Aurora, Colorado, 80045

  • Piedmont Physicians Georgia Lung

    Austell, Georgia, 30309

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Bay Area Cardiology Associates

    Brandon, Florida, 33511

  • St. Elizabeth's Medical Center

    Brighton, Massachusetts, 02135

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • St. Luke's Hospital

    Chesterfield, Missouri, 63017

  • University of Illinois at Chicago Hospital

    Chicago, Illinois, 60612

  • The Lindner Research Center The Christ Hospital Health Network

    Cincinnati, Ohio, 45219

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • National Jewish Health

    Denver, Colorado, 80206

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Inova Heart and Vascular Institute

    Falls Church, Virginia, 22042

  • Stern Cardiovascular Foundation

    Germantown, Tennessee, 38138

  • Spectrum Health Medical Group

    Grand Rapids, Michigan, 49503

  • Houston Methodist Research Institute

    Houston, Texas, 77030

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • Indiana University Health Methodist Research Institute, INC

    Indianapolis, Indiana, 46202

  • Community Physician Network, Heart and Vascular Care

    Indianapolis, Indiana, 46250

  • Saint Vincent Hospital and Health Services

    Indianapolis, Indiana, 46260

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 55242

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

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

    Jacksonville, Florida, 33204

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Summit Medical Group

    Knoxville, Tennessee, 37909

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17601

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky Medical Center

    Lexington, Kentucky, 40536

  • South Denver Cardiology

    Littleton, Colorado, 80120

  • VA Healthcare System of Greater Los Angeles

    Los Angeles, California, 90073

  • University of California Los Angeles Pulmonary Division

    Los Angeles, California, 90095

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90211

  • Kentuckiana Pulmonary Associates

    Louisville, Kentucky, 40202

  • University of Louisville Physicians Outpatient Center

    Louisville, Kentucky, 40202

  • Texas Tech University Health Sciences Center

    Lubbock, Texas, 79905

  • WellStar Medical Group

    Marietta, Georgia, 30060

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • West Virginia University Hospital

    Morgantown, West Virginia, 26506

  • Intermountain Medical Center

    Murray, Utah, 84157-7000

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Barnabas Health Lung Center

    Newark, New Jersey, 07112

  • Sentara Cardiovascular Research Institute

    Norfolk, Virginia, 23507

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453

  • Central Florida Pulmonary Group, P.A.

    Orlando, Florida, 32803

  • Florida Hospital

    Orlando, Florida, 32806

  • OSF HealthCare

    Peoria, Illinois, 61614

  • Banner University Medical Center Phoenix

    Phoenix, Arizona, 85006

  • Pinehurst Medical Clinic

    Pinehurst, North Carolina, 28374

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • The Oregon Clinic

    Portland, Oregon, 97225

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Carilion Clinic

    Roanoke, Virginia, 24014

  • University of California - Davis Medical Center

    Sacramento, California, 95817

  • Santa Barbara Cottage Hospital

    Santa Barbara, California, 93105

  • Chest Medicine Associates

    South Portland, Maine, 04106

  • Providence Medical Research Center

    Spokane, Washington, 99204

  • Pulmonary Health Physicians, PC

    Syracuse, New York, 13066

  • University of South Florida; Tampa General Hospital

    Tampa, Florida, 33606

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • University of Toledo Medical Center

    Toledo, Ohio, 43614

  • University of Arizona

    Tucson, Arizona, 85724

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Medical Faculty Associates, George Washington University

    Washington D.C., District of Columbia, 20037

  • Iowa Heart Center

    West Des Moines, Iowa, 50266

  • Cleveland Clinic of Florida

    Weston, Florida, 33331

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral Treprostinil in Subjects With Pulmonary Hypertension (PH) in Heart Failure With Preserved Ejection Fraction (HFpEF)

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.

Read the detailed description

Study TDE-HF-301 was a multicenter, randomized, double-blind, placebo-controlled study designed to investigate the effect of oral treprostinil compared with placebo on exercise capacity in subjects with WHO Group 2 PH associated with HFpEF.

Once randomized, subjects were dispensed study drug and took an initial dose (0.125 mg) at the study site on the day of randomization. Dosing of study drug continued at 0.125 mg 3 times daily (TID; every 6 to 8 hours) with food. Dose increases could occur in 0.125-mg increments every 72 hours at the discretion of the Investigator up to a maximum allowable dose of 6 mg TID. Subjects received oral treprostinil as 0.125, 0.25, 1.0, or 2.5 mg sustained-release osmotic tablets (maximum dose 6 mg TID) or matching placebo. Doses of study drug were to be increased in the absence of dose-limiting drug-related adverse events (AEs) to ensure that each subject received the optimal dose throughout the study. Subjects returned for visits at Weeks 6, 12, 18, and 24. Subjects who terminated study drug early were asked to complete all remaining study visits. The study had an adaptive design where the maximum allowable dose was 2 mg until the Data Monitoring Committee had confirmed a satisfactory safety profile. After this confirmation, the maximum allowable dose was increased to 4 mg TID. This occurred after 45 subjects had been enrolled. A subsequent Data Monitoring Committee meeting, which occurred after 75 subjects had been enrolled, increased the maximum allowable dose to 6 mg TID.

Efficacy assessments consisted of 6-Minute Walk Distance (6MWD), blood collection for N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, clinical worsening, WHO Functional Class (FC), Borg dyspnea score, glycated hemoglobin (HbA1c), and Kansas City Cardiomyopathy Questionnaire (KCCQ).

Safety assessments consisted of AEs, physical examinations, vital signs, 12-lead electrocardiograms (ECGs), echocardiograms (ECHOs), heart failure signs and symptoms, pregnancy testing, clinical laboratory tests, hospitalizations due to cardiopulmonary indication, and worsening heart failure as demonstrated by outpatient administration of intravenous (IV) diuretics. Subjects could have optionally provided samples for the evaluation of biomarkers and pharmacogenomics.

Subjects that completed the 24-week treatment period on study drug were permitted to enter the open-label extension study (Study TDE-HF-302).

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.

Being tested
Oral treprostinil, Placebo
Keywords
Pulmonary Hypertension, 6-Minute Walk Test, HFpEF, Oral Treprostinil
Medical subject headings
Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral treprostinilDrug

    Also called Treprostinil diethanolamine, treprostinil diolamine

    Sustained-release oral tablets for TID administration

  • PlaceboDrug

    Also called Matching placebo (sugar pill)

    Placebo (sugar pill) for TID oral administration

Study groups in NCT03037580
Study groupRoleWhat they receive
Oral treprostinilExperimentalSustained-release oral tablets for TID administration
Receives: Drug: Oral treprostinil
PlaceboPlacebo comparatorPlacebo (sugar pill) for TID oral administration
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to Week 24

Secondary outcomes (3)

  1. Change in NT-proBNP Levels From Baseline to Week 24

    The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function.

    Measured: Baseline to Week 24

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

    Clinical worsening was defined as the occurrence of any 1 of the following clinical worsening events: hospitalization due to a cardiopulmonary indication (a non-elective hospitalization lasting at least 24 hours in duration caused by clinical conditions directly related to PH and/or heart failure), outpatient administration of IV diuretics, death (all causes), decrease in 6MWD >15% from Baseline (or the subject was too ill to walk, and the cause was directly related to the disease under study) at 2 consecutive visits on different days (except Week 24).

    Measured: Baseline to Week 24

  3. Change in WHO FC From Baseline to Week 24

    The WHO functional classification ranges from I (subject's disease does not affect daily activities) to IV (subject's disease causes severe impairment).

    Measured: Baseline to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2017 (estimated)
  2. Study start15 Aug 2017
  3. Primary completion3 Dec 2019
  4. Study completion3 Dec 2019

Why it stopped: Terminated by sponsor

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03037580
Sponsor's protocol ID
TDE-HF-301
Status last verified
Oct 2020
First submitted
27 Jan 2017
Last updated
10 Nov 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oral treprostinil in people with Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction, run by United Therapeutics at 82 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 82 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in 6MWD From Baseline to Week 24 (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03037580.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2020.

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