Safety and Efficacy of Inhaled Treprostinil in Adult PH With ILD Including CPFE
A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Subjects With Pulmonary Hypertension Due to Parenchymal Lung Disease
1 other identifier
interventional
326
2 countries
97
Brief Summary
This was a multicenter, randomized (1:1 inhaled treprostinil: placebo), double-blinded, placebo-controlled trial to evaluate the safety and efficacy of inhaled treprostinil in subjects with pre-capillary pulmonary hypertension (PH) associated with interstitial lung disease (ILD) including combined pulmonary fibrosis and emphysema (CPFE). The study included 326 patients at approximately 120 clinical trial centers. The treatment phase of the study lasted approximately 16 weeks. Patients who completed all required assessments were eligible to enter an open-label, extension study (RIN-PH-202).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2017
Typical duration for phase_2
97 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 11, 2015
CompletedFirst Posted
Study publicly available on registry
December 15, 2015
CompletedStudy Start
First participant enrolled
February 3, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 26, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 26, 2019
CompletedResults Posted
Study results publicly available
July 13, 2021
CompletedJuly 27, 2022
July 1, 2022
2.9 years
December 11, 2015
April 29, 2021
July 21, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in 6-minute Walk Distance (6MWD) Measured at Peak Exposure From Baseline to Week 16
The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline to Week 16, correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status. Subjects will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Peak exposure 6MWD will occur by conducting 6-minute walk test (6MWT) within 10 to 60 minutes after the most recent dose of study drug dose.
Baseline and Week 16
Secondary Outcomes (4)
Change in Plasma Concentration of N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 16
Baseline and Week 16
Incidence of Clinical Worsening
Baseline to Week 16
Change in Peak 6-minute Walk Distance (6MWD) From Baseline to Week 12
Baseline and Week 12
Change in Trough 6-minute Walk Distance (6MWD) From Baseline to Week 15
Baseline and Week 15
Study Arms (2)
Placebo
PLACEBO COMPARATORMatching placebo inhaled using an ultrasonic nebulizer four times daily
Inhaled Treprostinil
ACTIVE COMPARATORActive Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled four times daily and titrated up to a maximum of 12 breaths four times daily
Interventions
Inhaled treprostinil (6 mcg/breath) administered four times daily
Eligibility Criteria
You may qualify if:
- Subject voluntarily gave informed consent to participate in the study.
- Males and females aged 18 years or older at the time of informed consent.
- a. Females of reproductive potential were non-pregnant (as confirmed by a urine pregnancy test at screening) and non-lactating, and: i. Abstained from intercourse (when in line with their preferred and usual lifestyle), or ii. Used 2 medically acceptable, highly effective forms of contraception for the duration of study, and at least 30 days after discontinuing study drug.
- b. Males with a partner of childbearing potential used condoms for the duration of treatment and for at least 48 hours after discontinuing study drug.
- The subject had a confirmed diagnosis of WHO Group 3 PH based on computed tomography (CT) imaging which was performed within 6 months prior to randomization and demonstrated evidence of diffuse parenchymal lung disease. Subjects had any form of ILD or CPFE.
- Subjects were required to have a right heart catheterization (RHC) within 1 year prior to randomization with the following documented parameters:
- Pulmonary vascular resistance (PVR) \>3 Wood Units (WU) and
- A pulmonary capillary wedge pressure (PCWP) of \<15 mmHg and
- A mean pulmonary arterial pressure (mPAP) of \>25 mmHg
- Baseline 6MWD ≥100 m.
- Subjects on a chronic medication for underlying lung disease (ie, pirfenidone, nintedanib, etc) were on a stable and optimized 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.
- Subjects with connective tissue disease (CTD) had a Baseline forced vital capacity (FVC) of \<70%.
You may not qualify if:
- The subject showed intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy.
- The subject received any PAH-approved therapy including: prostacyclin therapy (ie, epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), prostacyclin (IP) receptor agonist (selexipag), endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE5-I), or soluble guanylate cyclase (sGC) stimulator within 60 days of randomization.
- The subject had evidence of clinically significant left-sided heart disease as defined by:
- PCWP \>15 mmHg
- Left ventricular ejection fraction \<40%. Note: Subjects with abnormal left ventricular function attributable entirely to impaired left ventricular filling due to the effects of right ventricular overload (ie, right ventricular hypertrophy and/or dilatation) were not excluded.
- The subject was receiving \>10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
- Current use of any inhaled tobacco/marijuana products or significant history of drug abuse at the time of informed consent.
- Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of randomization.
- Initiation of pulmonary rehabilitation within 12 weeks prior to randomization.
- In the opinion of the Investigator, the subject had any condition that would interfere with the interpretation of study assessments or has any disease or condition (ie, peripheral vascular disease, musculoskeletal disorder, morbid obesity) that would likely be the primary limit to ambulation (as opposed to PH).
- Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to randomization.
- Severe concomitant illness limiting life expectancy (\<6 months).
- Acute pulmonary embolism within 90 days of randomization.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (97)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
IMC-Diagnostic & Medical Clinic
Mobile, Alabama, 36604, United States
Arizona Pulmonary Specialists, Ltd.
Phoenix, Arizona, 85012, United States
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013, United States
University of Arizona
Tucson, Arizona, 85724, United States
Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion
Beverly Hills, California, 90211, United States
University of California San Francisco - Fresno
Fresno, California, 93701, United States
University of California San Diego
La Jolla, California, 92093, United States
VA Long Beach Healthcare System
Long Beach, California, 90822, United States
University of Southern California Health Sciences
Los Angeles, California, 90033, United States
Department of Veterans Affairs Greater Los Angeles Healthcare System
Los Angeles, California, 90073, United States
Pacific Pulmonary Medical Group
Riverside, California, 92505, United States
Kaiser Permanente - Roseville
Roseville, California, 95825, United States
University of California Davis Medical Center
Sacramento, California, 95817, United States
Kaiser Permanente
San Francisco, California, 94115, United States
University of Colorado Hospital - Cardiac and Vascular Center
Aurora, Colorado, 80045, United States
National Jewish Health
Denver, Colorado, 80206, United States
Yale New Haven Hospital
New Haven, Connecticut, 06510, United States
Medstar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
Florida Lung, Asthma & Sleep Specialists, P.A.
Celebration, Florida, 34747, United States
St. Francis Sleep, Allergy and Lung Institute
Clearwater, Florida, 33765, United States
University of Florida Clinical Research Center
Gainesville, Florida, 32610, United States
University of Florida College of Medicine, Jacksonville
Jacksonville, Florida, 32209, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
St. Vincent's Health System
Jacksonville, Florida, 33204, United States
University of Miami
Miami, Florida, 33136, United States
Florida Hospital
Orlando, Florida, 32804, United States
South Miami Heart Specialists
South Miami, Florida, 33143, United States
Tampa General Hospital Center of Research Excellence
Tampa, Florida, 33606, United States
Cleveland Clinic Florida
Weston, Florida, 33331, United States
The Emory Clinic
Atlanta, Georgia, 30322, United States
Piedmont - Georgia Lung Associates
Austell, Georgia, 30106, United States
Wellstar Medical Group - Pulmonary Medicine
Marietta, Georgia, 30060, United States
Northwestern University School of Medicine
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Illinois at Chicago Hospital
Chicago, Illinois, 60612, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
U Health Physicians Advanced Heart and Lung Clinic
Indianapolis, Indiana, 46202, United States
Community Heart and Vascular Hospital East
Indianapolis, Indiana, 46250, United States
St. Vincent Medical Group, Inc.
Indianapolis, Indiana, 46260, United States
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
University of Kentucky Medical Center
Lexington, Kentucky, 40536, United States
University of Louisville Clinical Trials Unit
Louisville, Kentucky, 40202, United States
Louisiana State University Health Sciences Center New Orleans
New Orleans, Louisiana, 70112, United States
Chest Medicine Associates
South Portland, Maine, 04106, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Johns Hopkins University Pulmonary and Critical Care Medicine
Baltimore, Maryland, 21205, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
Spectrum Health Heart and Lung Specialized Care Clinic
Grand Rapids, Michigan, 49503, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
The University of New Mexico Clinical and Translational Science Center
Albuquerque, New Mexico, 87131, United States
Albany Medical College
Albany, New York, 12208, United States
New York Methodist Hospital
Brooklyn, New York, 11215, United States
Northwell Health
New Hyde Park, New York, 11040, United States
NYU Langone Medical Center
New York, New York, 10016, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
New York Presbyterian - Weill Cornell Medical Center
New York, New York, 10065, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center-Duke South Clinic
Durham, North Carolina, 27710, United States
Pinehurst Medical Clinic, Inc.
Pinehurst, North Carolina, 28374, United States
The Lindner Research Center at The Christ Hospital
Cincinnati, Ohio, 45219, United States
University of Cincinnati Health
Cincinnati, Ohio, 45267, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
The Ohio State University Medical Center
Columbus, Ohio, 43221, United States
INTEGRIS Baptist Medical Center
Oklahoma City, Oklahoma, 73112, United States
Penn Medicine University City
Philadelphia, Pennsylvania, 19104, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
UPMC Montifiore University Hospital
Pittsburgh, Pennsylvania, 15213, United States
AnMed Health Medical Center
Anderson, South Carolina, 29621, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Statcare Pulmonary Consultants
Knoxville, Tennessee, 37919, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
Texas Tech University Health Sciences Center
El Paso, Texas, 79905, United States
Houston Methodist
Houston, Texas, 77030, United States
Memoral Hermann Hospital - Texas Medical Center
Houston, Texas, 77030, United States
Michael E. DeBakey VA Medical Center
Houston, Texas, 77030, United States
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Vermont Lung Center
Colchester, Vermont, 05446, United States
Inova Fairfax Medical Campus
Fairfax, Virginia, 22042, United States
Sentara Norfolk General Hospital
Norfolk, Virginia, 23507, United States
Pulmonary Associates of Richmond
Richmond, Virginia, 23229, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin, 53792, United States
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53215, United States
Medical College of Wisconsin/Froedtert Hospital
Milwaukee, Wisconsin, 53226, United States
Auxilio Mutuo Hospital
Guaynabo, 00968, Puerto Rico
Related Publications (3)
Nathan SD, Deng C, King CS, DuBrock HM, Elwing J, Rajagopal S, Rischard F, Sahay S, Broderick M, Shen E, Smith P, Tapson VF, Waxman AB. Inhaled Treprostinil Dosage in Pulmonary Hypertension Associated With Interstitial Lung Disease and Its Effects on Clinical Outcomes. Chest. 2023 Feb;163(2):398-406. doi: 10.1016/j.chest.2022.09.007. Epub 2022 Sep 15.
PMID: 36115497DERIVEDNathan SD, Waxman A, Rajagopal S, Case A, Johri S, DuBrock H, De La Zerda DJ, Sahay S, King C, Melendres-Groves L, Smith P, Shen E, Edwards LD, Nelsen A, Tapson VF. Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: a post-hoc analysis of the INCREASE study. Lancet Respir Med. 2021 Nov;9(11):1266-1274. doi: 10.1016/S2213-2600(21)00165-X. Epub 2021 Jun 29.
PMID: 34214475DERIVEDWaxman A, Restrepo-Jaramillo R, Thenappan T, Ravichandran A, Engel P, Bajwa A, Allen R, Feldman J, Argula R, Smith P, Rollins K, Deng C, Peterson L, Bell H, Tapson V, Nathan SD. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. N Engl J Med. 2021 Jan 28;384(4):325-334. doi: 10.1056/NEJMoa2008470. Epub 2021 Jan 13.
PMID: 33440084DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- United Therapeutics Global Medical Information
- Organization
- United Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- 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
December 11, 2015
First Posted
December 15, 2015
Study Start
February 3, 2017
Primary Completion
December 26, 2019
Study Completion
December 26, 2019
Last Updated
July 27, 2022
Results First Posted
July 13, 2021
Record last verified: 2022-07