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Pulmonary HypertensionPhase 2/3NCT02630316

Safety and Efficacy of Inhaled Treprostinil in Adult PH With ILD Including CPFE

A Phase 2/3 study testing Inhaled Treprostinil in people with Pulmonary Hypertension and Interstitial Lung Disease, run by United Therapeutics at 97 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Inhaled Treprostinil
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
326 participants
Where
97 sitesin 2 countries
Study dates
3 Feb 2017to 26 Dec 2019
Phase
Phase 2/3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject voluntarily gave informed consent to participate in the study.
  • Males and females aged 18 years or older at the time of informed consent.
  • 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.
  • 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:
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  • 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%.

Who cannot join

  • The subject had a diagnosis of PAH or PH for reasons other than WHO Group 3 PH ILD as outlined in Inclusion Criterion 3.
  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

97 sites in 2 countries.

97 sites in 2 countries

United States96 sites

  • Albany Medical College

    Albany, New York, 12208

  • The University of New Mexico Clinical and Translational Science Center

    Albuquerque, New Mexico, 87131

  • AnMed Health Medical Center

    Anderson, South Carolina, 29621

  • The Emory Clinic

    Atlanta, Georgia, 30322

  • University of Colorado Hospital - Cardiac and Vascular Center

    Aurora, Colorado, 80045

  • Piedmont - Georgia Lung Associates

    Austell, Georgia, 30106

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University Pulmonary and Critical Care Medicine

    Baltimore, Maryland, 21205

  • Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion

    Beverly Hills, California, 90211

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • New York Methodist Hospital

    Brooklyn, New York, 11215

  • Florida Lung, Asthma & Sleep Specialists, P.A.

    Celebration, Florida, 34747

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University School of Medicine

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Illinois at Chicago Hospital

    Chicago, Illinois, 60612

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • The Lindner Research Center at The Christ Hospital

    Cincinnati, Ohio, 45219

  • University of Cincinnati Health

    Cincinnati, Ohio, 45267

  • St. Francis Sleep, Allergy and Lung Institute

    Clearwater, Florida, 33765

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Vermont Lung Center

    Colchester, Vermont, 05446

  • The Ohio State University Medical Center

    Columbus, Ohio, 43221

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • National Jewish Health

    Denver, Colorado, 80206

  • Duke University Medical Center-Duke South Clinic

    Durham, North Carolina, 27710

  • Texas Tech University Health Sciences Center

    El Paso, Texas, 79905

  • Inova Fairfax Medical Campus

    Fairfax, Virginia, 22042

  • University of California San Francisco - Fresno

    Fresno, California, 93701

  • University of Florida Clinical Research Center

    Gainesville, Florida, 32610

  • Spectrum Health Heart and Lung Specialized Care Clinic

    Grand Rapids, Michigan, 49503

  • Houston Methodist

    Houston, Texas, 77030

  • Memoral Hermann Hospital - Texas Medical Center

    Houston, Texas, 77030

  • Michael E. DeBakey VA Medical Center

    Houston, Texas, 77030

  • U Health Physicians Advanced Heart and Lung Clinic

    Indianapolis, Indiana, 46202

  • Community Heart and Vascular Hospital East

    Indianapolis, Indiana, 46250

  • St. Vincent Medical Group, Inc.

    Indianapolis, Indiana, 46260

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Florida College of Medicine, Jacksonville

    Jacksonville, Florida, 32209

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • St. Vincent's Health System

    Jacksonville, Florida, 33204

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Statcare Pulmonary Consultants

    Knoxville, Tennessee, 37919

  • University of California San Diego

    La Jolla, California, 92093

  • University of Kentucky Medical Center

    Lexington, Kentucky, 40536

  • VA Long Beach Healthcare System

    Long Beach, California, 90822

  • University of Southern California Health Sciences

    Los Angeles, California, 90033

  • Department of Veterans Affairs Greater Los Angeles Healthcare System

    Los Angeles, California, 90073

  • University of Louisville Clinical Trials Unit

    Louisville, Kentucky, 40202

  • University of Wisconsin School of Medicine and Public Health

    Madison, Wisconsin, 53792

  • Wellstar Medical Group - Pulmonary Medicine

    Marietta, Georgia, 30060

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • University of Miami

    Miami, Florida, 33136

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin/Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • IMC-Diagnostic & Medical Clinic

    Mobile, Alabama, 36604

  • Yale New Haven Hospital

    New Haven, Connecticut, 06510

  • Northwell Health

    New Hyde Park, New York, 11040

  • Louisiana State University Health Sciences Center New Orleans

    New Orleans, Louisiana, 70112

  • NYU Langone Medical Center

    New York, New York, 10016

  • Mount Sinai Medical Center

    New York, New York, 10029

  • New York Presbyterian - Weill Cornell Medical Center

    New York, New York, 10065

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • INTEGRIS Baptist Medical Center

    Oklahoma City, Oklahoma, 73112

  • Florida Hospital

    Orlando, Florida, 32804

  • Penn Medicine University City

    Philadelphia, Pennsylvania, 19104

  • Arizona Pulmonary Specialists, Ltd.

    Phoenix, Arizona, 85012

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Pinehurst Medical Clinic, Inc.

    Pinehurst, North Carolina, 28374

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • UPMC Montifiore University Hospital

    Pittsburgh, Pennsylvania, 15213

  • Pulmonary Associates of Richmond

    Richmond, Virginia, 23229

  • Pacific Pulmonary Medical Group

    Riverside, California, 92505

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Kaiser Permanente - Roseville

    Roseville, California, 95825

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • The University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Kaiser Permanente

    San Francisco, California, 94115

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • South Miami Heart Specialists

    South Miami, Florida, 33143

  • Chest Medicine Associates

    South Portland, Maine, 04106

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Tampa General Hospital Center of Research Excellence

    Tampa, Florida, 33606

  • University of Arizona

    Tucson, Arizona, 85724

  • Medstar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Cleveland Clinic Florida

    Weston, Florida, 33331

Other trials in United States

Puerto Rico1 site

  • Auxilio Mutuo Hospital

    Guaynabo, 00968

Other trials in Puerto Rico

About this study

Official title: 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

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).

Read the detailed description

Study RIN-PH-201 was a multicenter, randomized, double-blind, placebo controlled, 16 week, parallel group study designed to investigate the safety and efficacy of inhaled treprostinil in subjects with PH-ILD. Subjects initiated inhaled treprostinil or placebo at a dose of 3 breaths (18 mcg) 4 times daily (QID) (during waking hours). Study drug doses were maximized throughout the study. Dose escalations (additional 1 breath QID) could occur up to every 3 days with a target dosing regimen of 9 breaths (54 mcg) QID and a maximum dose of 12 breaths (72 mcg) QID, as clinically tolerated. Subjects were assessed during Screening and Baseline to determine eligibility for the study. Once eligible, 5 Treatment Phase visits to the clinic were required at Week 4, Week 8, Week 12, Week 15, and Week 16 (final study visit). An Early Termination (ET) Visit was conducted for subjects who discontinued prior to Week 16; all assessments planned for the final Week 16 Visit were conducted during the ET Visit, if applicable. Subjects were contacted at least weekly by telephone or email to assess tolerance to study drug, AEs, and changes to concomitant medications. Efficacy assessments consisted of 6-minute walk distance (6MWD), plasma N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentration, and incidence of clinical worsening. Exploratory endpoints included change in St. George's Respiratory Questionnaire (SGRQ), change in distance saturation product (DSP), time to exacerbation of underlying lung disease, and pulmonary function tests (PFT). Safety assessments consisted of the development of AEs, vital signs, clinical laboratory parameters, ECG parameters, hospitalizations due to cardiopulmonary indications, exacerbations of underlying lung disease, and oxygenation. Subjects who remained on study drug, completed all assessments during the 16-week Treatment Phase, and met all eligibility criteria were eligible for the open-label extension study (RIN-PH-202). Additionally, subjects who withdrew from study drug prior to Week 16 due to clinical worsening and returned to the clinic for scheduled visits (excluding the Week 15 Visit) were eligible for RIN PH-202.

Being tested
Inhaled Treprostinil, Placebo
Keywords
Treprostinil, PH, ILD, CPFE, 6 Minute Walk Test
Medical subject headings
Hypertension, Pulmonary, Lung Diseases, Interstitial, Emphysema

What participants receive

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

  • Inhaled TreprostinilDrug

    Also called Tyvaso

    Inhaled treprostinil (6 mcg/breath) administered four times daily

  • PlaceboDrug

    Placebo administered four times daily

Study groups in NCT02630316
Study groupRoleWhat they receive
PlaceboPlacebo comparatorMatching placebo inhaled using an ultrasonic nebulizer four times daily
Receives: Drug: Placebo
Inhaled TreprostinilActive 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
Receives: Drug: Inhaled Treprostinil

What is being measured

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

  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.

    Measured: Baseline and Week 16

Secondary outcomes (4)

  1. Change in Plasma Concentration of N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 16

    The NT-proBNP serum concentration is a useful biomarker associated with changes in right heart morphology and function. NT-proBNP serum concentration will be assessed to compare the severity of heart failure at Baseline and Week 16. Blood for NT-proBNP assessment must be drawn prior to conducting the 6MWT.

    Measured: Baseline and Week 16

  2. Incidence of Clinical Worsening

    Subjects were monitored for clinical worsening from the time of randomization until 1 of the following criteria were met: hospitalization due to a cardiopulmonary indication; decrease in 6MWD >15% from Baseline directly related to the disease under study, at 2 consecutive visits and at least 24 hours apart; death (all causes); or lung transplantation.

    Measured: Baseline to Week 16

  3. Change in Peak 6-minute Walk Distance (6MWD) From Baseline to Week 12

    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 12, 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 6MWT within 10 to 60 minutes after the most recent dose of study drug dose.

    Measured: Baseline and Week 12

  4. Change in Trough 6-minute Walk Distance (6MWD) From Baseline to Week 15

    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 15, 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. Distance <500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance >800 meters (with no rests) suggests mild or no limitation. Trough exposure 6MWD will occur by conducting 6-minute walk test (6MWT) at least four hours after the most recent study drug dose.

    Measured: Baseline and Week 15

Timeline

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

  1. First posted15 Dec 2015 (estimated)
  2. Study start3 Feb 2017
  3. Primary completion26 Dec 2019
  4. Study completion26 Dec 2019

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
326 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02630316
Sponsor's protocol ID
RIN-PH-201
Status last verified
Jul 2022
First submitted
11 Dec 2015
Last updated
27 Jul 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36115497

  • Nathan 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.

    PubMed 34214475

  • Waxman 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.

    PubMed 33440084

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Inhaled Treprostinil in people with Pulmonary Hypertension and Interstitial Lung Disease, run by United Therapeutics at 97 sites in 2 countries.

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 13 inclusion and 14 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: finished, as of the sponsor's last update on 27 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 97 sites in United States, Puerto Rico. 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 13 Jul 2021). 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 6-minute Walk Distance (6MWD) Measured at Peak Exposure From Baseline to Week 16 (time frame: Baseline and Week 16). 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 NCT02630316, which also lists 3 linked publications.

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 27 Jul 2022.

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