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

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ClinicalTrials.gov Identifier: NCT03037580
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : March 7, 2019
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Brief Summary:
This is 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 will take the initial dose of study drug at the study site on the day of randomization. Subjects will return to the study site for visits scheduled at Weeks 6, 12, 18, and 24. The treatment phase of the study will last approximately 24 weeks.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Heart Failure With a Preserved Ejection Fraction Drug: Oral treprostinil Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 15, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Oral treprostinil
Sustained-release oral tablets for three times daily (TID) administration
Drug: Oral treprostinil
Sustained-release oral tablets for TID administration
Other Name: Treprostinil diethanolamine

Placebo Comparator: Placebo
Placebo (sugar pill) for TID oral administration
Drug: Placebo
Placebo (sugar pill) for TID oral administration
Other Name: Matching placebo (sugar pill)




Primary Outcome Measures :
  1. Change in 6-Minute Walk Distance (6MWD) from Baseline to Week 24 [ Time Frame: 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.


Secondary Outcome Measures :
  1. Change in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Levels from Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]
    The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function.

  2. Time to the First Clinical Worsening Event Over the 24-week Treatment Period [ Time Frame: Baseline to Week 24 ]
    Clinical worsening is 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 intravenous diuretics, death (all causes), decrease in 6MWD >15% from Baseline (or the subject is too ill to walk, and the cause is directly related to the disease under study) at 2 consecutive visits on different days (except Week 24).

  3. Change in WHO Functional Class from Baseline to Week 24 [ Time Frame: 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).



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A subject can qualify if they have undergone a right heart catheterization (RHC) within 180 days of Baseline.
  2. The subject has a diagnosis of heart failure with a left ventricular ejection fraction (LVEF) ≥45% by echocardiogram (ECHO) completed during Screening (prior to randomization).
  3. The subject's baseline 6MWD must be at least 150 meters.
  4. The subject has pulmonary function tests conducted within 6 months of Screening or during the Screening phase.
  5. Subjects on a chronic medication for heart failure must be on a stable dose for ≥30 days prior to randomization.
  6. Subjects on chronic medications for any underlying respiratory condition must be on a stable dose for ≥30 days prior to randomization.

Exclusion Criteria:

  1. The subject is pregnant or lactating.
  2. In the opinion of the Principal Investigator, the subject has a primary diagnosis of PH other than WHO Group 2 PH.
  3. The subject has 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.
  4. The subject has received any approved PAH therapies within 30 days of randomization. Chronic use of an approved phosphodiesterase type 5 inhibitor (PDE5-I) is allowed as long as the subject has been on a stable dose for at least 90 days prior to randomization and has had an RHC confirming the parameters necessary for inclusion in the study after being on a stable PDE5-I dose for at least 30 days.
  5. The subject has been hospitalized for a cardiopulmonary indication within 30 days of randomization.
  6. The subject had a myocardial infarction within 90 days of randomization.
  7. The subject had cardiac resynchronization therapy within 90 days of randomization or anticipated resynchronization therapy during the study treatment period.
  8. The subject has 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.
  9. The subject has uncontrolled systemic hypertension, systolic blood pressure <100 mmHg, or a resting heart rate >100 beats per minute at Baseline.
  10. The subject has known genetic hypertrophic cardiomyopathy, sarcoidosis, or cardiac amyloidosis.
  11. The subject has 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) is allowed.
  12. The subject has 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)
  13. The subject has a Body Mass Index >45 kg/m^2.
  14. The subject has any musculoskeletal disorder, or has any other condition that limits ambulation.
  15. The subject has end-stage renal disease requiring/receiving dialysis.
  16. The subject participated in an investigational drug or device study within 30 days prior to signing consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03037580


Contacts
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Contact: David B Yehle, RPh 919 485-8350 dyehle@unither.com
Contact: Louis Holdstock, PhD 919 485-8350 lholdstock@unither.com

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Sponsors and Collaborators
United Therapeutics

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Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT03037580     History of Changes
Other Study ID Numbers: TDE-HF-301
First Posted: January 31, 2017    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by United Therapeutics:
Pulmonary Hypertension
6-Minute Walk Test
HFpEF
Oral Treprostinil

Additional relevant MeSH terms:
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Hypertension
Heart Failure
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases
Treprostinil
Antihypertensive Agents