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Pulmonary HypertensionPhase 3PERFECTNCT03496623

A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Participants With Pulmonary Hypertension (PH) Due to Chronic Obstructive Pulmonary Disease (COPD)

A Phase 3 study testing Inhaled treprostinil solution in people with Pulmonary Hypertension and Chronic Obstructive Pulmonary Disease, run by United Therapeutics at 76 sites in 4 countries.

Terminated

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

Official record
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Trial summary

The primary objective of this study is to demonstrate the efficacy of inhaled treprostinil compared to placebo in improving exercise ability as measured by change from baseline in 6-Minute Walk Distance (6MWD) following 12 weeks of active treatment in participants with PH-COPD. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Inhaled treprostinil solution
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
188 participants
Where
76 sitesin 4 countries
Study dates
8 May 2018to 13 Oct 2022
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants who meet the following criteria may be included in the study:
  • Participant voluntarily gives informed consent to participate in the study.
  • Males and females 18 years of age and above at the time of informed consent.
  • Women of childbearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must agree to practice abstinence or use 2 highly effective methods of contraception (defined as a method of birth control that results in a low failure rate, [<1% per year], such as approved hormonal contraceptives, barrier methods [such as condom or diaphragm] used with a spermicide, or an intrauterine device) for the duration of study treatment and for 48 hours after discontinuing study drug. Participants must have a negative pregnancy test at the Screening Visit 1 (urine [prior to the first dose of study medication] and serum) and Baseline Visit (Study Week 1) (urine).
  • Males with a partner of childbearing potential must agree to use a barrier method (condom) with a spermicide for the duration of treatment and for at least 48 hours after discontinuing study drug.
  • Diagnosis of PH-COPD (World Heath Organization [WHO] Group 3).
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  • Clinical diagnosis of COPD will be made using the Global Initiative for Chronic
  • Obstructive Lung Disease (GOLD) diagnostic criteria (GOLD Criteria 2020) and spirometry with the following documented parameters measured during Screening Visit 1 (prior to start of low-dose inhaled treprostinil):
  • Forced expiratory volume in 1 second (FEV1) <80% predicted
  • FEV1/Forced vital capacity (FVC) <70
  • The participant has a resting saturation peripheral capillary oxygenation (SpO2) greater than or equal to 90%, with or without supplemental oxygen, but not to exceed 10 liters (L)/min oxygen supplementation by any mode of delivery during Screening Visit 1.
  • During Screening Visit 1 prior to start of low-dose inhaled treprostinil, a 6MWD greater than or equal to 100 meters.
  • Have a right heart catheterization (RHC) performed during Screening Visit 1. (A previous RHC obtained within 12 months prior to the start of Screening Visit 1 is acceptable for determining eligibility, even if done without oxygen or vasodilator challenge, and a repeat RHC is not required.) The following parameters must be documented for eligibility:
  • Pulmonary vascular resistance (PVR) greater than or equal to 4 Wood units
  • A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of less than or equal to 15 millimeters of mercury (mmHg)
  • A Pulmonary artery pressure mean (PAPm) of greater than or equal to 30 mmHg
  • Participants must be on a stable and optimized dose of chronic COPD medications for greater than or equal to 30 days prior to start of Screening Visit 1 and remain on the same dose throughout the Screening Period.
  • In the opinion of the Investigator, the participant can communicate effectively with study personnel and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.

Who cannot join

  • The following will exclude participants from the study:
  • The participant has a diagnosis of either pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) due to reasons other than COPD. This would include, but is not limited to, chronic thromboembolic PH or acute/recent deep vein thrombosis or pulmonary embolism, untreated or inadequately treated obstructive sleep apnea, connective tissue disease (including but not limited to systemic sclerosis/scleroderma or systemic lupus erythematosus), sarcoidosis, human immunodeficiency virus-1 infection, and other conditions under WHO Group 1, 2, 4, and 5 classifications.
  • Based on chest computed tomography (CT) imaging during Screening Visit 1, the participant has a confirmed diagnosis of WHO Group 3 PH, other than COPD, such as idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, diffuse parenchymal lung disease or interstitial lung disease. A previous chest CT scan performed within the 6 months prior to the start of Screening Visit 1 is also acceptable, and a repeat assessment is not required.
  • A redacted CT scan report (from Screening Visit 1 or dated within prior 6 months) should be provided to the Medical Monitor with the Pre-Baseline Review Form to confirm eligibility.
  • The participant has received any Food and Drug Administration (FDA)-approved medication for the treatment of PAH (that is, prostacyclin, prostacyclin receptor agonist, endothelin receptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I], or soluble guanylate cyclase [sGC] stimulator) at Screening Visit 1 and thereafter, except if received for acute vasoreactivity testing.
  • The participant has a previous diagnosis of homozygous alpha-1 antitrypsin deficiency.
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  • The participant has any prior intolerance to inhaled prostanoid therapy.
  • Inability to tolerate low-dose (3 breaths, 18 mcg) study drug and/or inability to follow dosing regimen during the Screening Period (pre-randomization).
  • Unwilling or unable to use Sponsor-provided devices (actigraph, spirometer, or smart device).
  • The participant has evidence of clinically significant left-sided heart disease (including but not limited to left ventricular ejection fraction <40%, left ventricular hypertrophy,) or clinically significant cardiologic conditions, such as congestive heart failure, coronary artery disease, or valvular heart disease. Note: Participants with abnormal left ventricular function attributable to the effects of right ventricular overload will not be excluded, but a discussion with and approval by the Sponsor Medical Monitor is needed.
  • Any exacerbation of COPD (including hospitalization or outpatient therapy) or active pulmonary or upper respiratory infection 60 days prior to start of Screening Visit 1 through the Baseline Visit. This is defined as worsening of respiratory symptoms that required treatment with corticosteroids and/or antibiotics.
  • Initiation of pulmonary rehabilitation within 12 weeks prior to start of Screening Visit 1 or, in the opinion of the Investigator, pulmonary rehabilitation is likely to be needed during the study Treatment Period.
  • The participant has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
  • The participant has any musculoskeletal disorder (severe arthritis of the lower limbs which limits ambulation, recent hip or knee joint replacement, artificial leg) or any other condition that would likely be the primary limitation to ambulation.
  • Use of any other investigational drug or device within 30 days prior to the start of Screening Visit 1.
  • Any other clinically significant illness or abnormal laboratory value(s) measured during the Screening Period that, in the opinion of the Investigator, might adversely affect the interpretation of the study data or safety of the participant.

Trial locations and contacts

76 sites in 4 countries.

76 sites in 4 countries

United States65 sites

  • Albany Medical College

    Albany, New York, 12208

  • The University of New Mexico

    Albuquerque, New Mexico, 87106

  • Pulmonary & Critical Care of Atlanta

    Atlanta, Georgia, 30342

  • University of Colorado Health Sciences Center

    Aurora, Colorado, 80045

  • Georgia Clinical Research

    Austell, Georgia, 30106

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • The University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27517

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Illinois Medical Center

    Chicago, Illinois, 60612

  • The Carl and Edyth Lindner Research Center at the Christ Hospital

    Cincinnati, Ohio, 45219

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • St. Francis Medical Institute

    Clearwater, Florida, 33765

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Detroit Medical Center Lung Institute

    Detroit, Michigan, 48201

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Clinical Research Associates of Central PA, LLC

    DuBois, Pennsylvania, 15801

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Texas Tech

    El Paso, Texas, 79905

  • Advocate Aurora Health Care

    Elmhurst, Illinois, 60126

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • University of Florida Clinical Research Center

    Gainesville, Florida, 32610

  • Spectrum Health

    Grand Rapids, Michigan, 49546

  • Hartford Hospital

    Hartford, Connecticut, 06106

  • Indiana University Healh North Hospital

    Indianapolis, Indiana, 46202

  • St. Vincent Medical Group, Inc.

    Indianapolis, Indiana, 46260

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

    Jacksonville, Florida, 32204

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Pulmonary Disease Specialists

    Kissimmee, Florida, 34741

  • Statcare Pulmonary Consultants

    Knoxville, Tennessee, 37909

  • University of Kentucky Medical Center

    Lexington, Kentucky, 40536

  • Advocate Condell Medical Center

    Libertyville, Illinois, 60048

  • South Denver Cardiology

    Littleton, Colorado, 80120

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • University of Southern California

    Los Angeles, California, 90033

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • West Los Angeles VA Healthcare Center

    Los Angeles, California, 90073

  • Kentuckiana Pulmonary Associates

    Louisville, Kentucky, 40202

  • University of Louisville Research Foundation

    Louisville, Kentucky, 40202

  • University of Wisconsin School of Medicine and Public Health

    Madison, Wisconsin, 53792

  • University of Miami Hospital

    Miami, Florida, 33136

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • The Mount Sinai Hospital

    New York, New York, 10029

  • Advocate Heart Institute & Pulmonology

    Normal, Illinois, 06176

  • Edward Heart Hospital

    Oakbrook Terrace, Illinois, 60181

  • Temple Lung Center

    Philadelphia, Pennsylvania, 19140

  • Banner University Medical Center

    Phoenix, Arizona, 85006

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • University of Pittsburgh Medical Center - Montefiore

    Pittsburgh, Pennsylvania, 15213

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Pulmonary Associates of Richmond, Inc.

    Richmond, Virginia, 23230

  • Carilion Clinic

    Roanoke, Virginia, 24014

  • University of Rochester Medical Center

    Rochester, New York, 14623

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • Santa Barbara Pulmonary Associates

    Santa Barbara, California, 93102

  • University of South Florida

    Tampa, Florida, 33606

  • Beaumont Health

    Troy, Michigan, 48085

  • University of Arizona Clinical and Translational Science (CATS) Research Center

    Tucson, Arizona, 85724

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Clear Lake Specialties/Tranquility Research

    Webster, Texas, 77598

Other trials in United States

Argentina6 sites

  • Hospital Britanico de Buenos Aires

    Buenos Aires, 1280AEB

  • El Cruce Hospital

    Buenos Aires

  • Fundacion Favaloro

    Ciudad Autonoma Buenos Aires, C1093AAS

  • Hospital Italiano de Buenos Aires

    Ciudad Autonoma Buenos Aires, C1093AAS

  • Hospital Italiano de Cordoba

    Córdoba

  • Centro Medico 21 de Diciembre

    Santa Fe

Other trials in Argentina

Israel4 sites

  • Lady Davis Carmel Medical Centre

    Haifa, 34362

  • Hadassah-Hebrew University Hospital

    Jerusalem, 9112001

  • Rabin Medical Center

    Petah Tiva, 49100

  • The Chaim Sheba Medical Center

    Tel HaShomer, 52621

Other trials in Israel

Puerto Rico1 site

  • CardioPulmonary Research Center

    Guaynabo, 00968

Other trials in Puerto Rico

About this study

Official title: A Phase 3, Randomized, Placebo-controlled, Double-blind, Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (PH-COPD)

The primary objective of this study is to demonstrate the efficacy of inhaled treprostinil compared to placebo in improving exercise ability as measured by change from baseline in 6-Minute Walk Distance (6MWD) following 12 weeks of active treatment in participants with PH-COPD.

Read the detailed description

This is a multicenter, randomized, double-blind, placebo-controlled, 34-week, cross-over study, with a Treatment Period of approximately 26 weeks under the Original Crossover Design or, if applicable, a 21-week parallel study, with a Treatment Period of approximately 14 weeks under the Contingent Parallel Design.

Being tested
Inhaled treprostinil solution, Placebo solution
Keywords
Pulmonary Hypertension, COPD, Inhaled Treprostinil, 6-Minute Walk Test, Tyvaso
Medical subject headings
Hypertension, Pulmonary, Pulmonary Disease, Chronic Obstructive

What participants receive

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

  • Inhaled treprostinil solutionDrug

    Treprostinil inhalation solution

  • Placebo solutionDrug

    Placebo solution

Study groups in NCT03496623
Study groupRoleWhat they receive
Inhaled TreprostinilExperimentalInhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 micrograms [mcg]) 4 times daily (QID)
Receives: Drug: Inhaled treprostinil solution
PlaceboPlacebo comparatorPlacebo delivered via an ultrasonic nebulizer for QID administration
Receives: Drug: Placebo solution

What is being measured

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

  1. Change From Baseline to Week 12 in 6-Minute Walk Distance (6MWD)

    6 MWD was calculated at peak exposure (10 to 60 minutes after dosing). 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course for 6 minutes (timed) and the distance walked (in meters) was recorded. Statistical analyses were not performed due to lack of appropriate sample size.

    Measured: Baseline, Week 12

Secondary outcomes (8)

  1. Change From Baseline to Week 12 in Moderate to Vigorous Physical Activity (MVPA)

    MVPA was defined as the number of minutes spent in moderate to vigorous physical activity as measured via a wrist-worn medical grade physical activity monitor. The screening data were used to establish a baseline level of physical activity.

    Measured: Baseline, Week 12

  2. Change From Baseline to Week 12 in Overall Activity

    Overall activity was defined as the number of minutes spent in overall activity (non-sedentary activity) as measured via a wrist-worn medical grade physical activity monitor. The screening data will be used to establish a baseline level of physical activity.

    Measured: Baseline, Week 12

  3. Change From Baseline to Week 12 in Borg Dyspnea Score

    The Borg Dyspnea Score was a 11-point scale rating the maximum level of dyspnea experienced during the 6-minute walking test (6MWT). Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea), with lower scores indicating a less exertion (a better outcome). The Borg Dyspnea Score was to be evaluated immediately after the 6MWT.

    Measured: Baseline, Week 12

  4. Change From Baseline to Week 12 in 6MWD/Borg Dyspnea Composite Score

    6MWD was calculated at peak exposure (10 to 60 minutes after dosing). 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course for 6 minutes (timed) and the distance walked (in meters) was recorded. The Borg Dyspnea Score was an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea), with lower scores indicating less exertion (a better outcome). The Borg Dyspnea Score was to be evaluated immediately after the 6MWT. The average 6WMWD data and the average Borg Dyspnea Composite Score data were summed and reported as the composite score.

    Measured: Baseline, Week 12

  5. Change From Baseline to Week 12 in Quality of Life (QOL) Measured by St. George's Respiratory Questionnaire (SGRQ)

    The SGRQ is a designed to measure how breathing impacts overall health, daily life, and perceived well-being in participants with obstructive airways disease. Scores range from 0 to 100, with lower scores indicating a better QoL.

    Measured: Baseline, Week 12

  6. Change From Baseline to Week 12 in QOL Measured by the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)

    The UCSD SOBQ is a self-administered rating of dyspnea associated with activities of daily living. The questionnaire uses a 6-point scale where 0 = "not at all" and 5 = "maximal or unable to do because of breathlessness". Lower scores indicate a better QoL.

    Measured: Baseline, Week 12

  7. Change From Baseline to Week 12 in Plasma Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Levels

    The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function. Improvement is defined as a decrease in the NT-proBNP plasma concentration.

    Measured: Baseline, Week 12

  8. Change From Baseline to Week 12 in Patient Global Assessment (PGA)

    The PGA is used to rate participant fatigue and shortness of breath. Participants will use the Sponsor-provided smart device for at-home capture of PGA data. The PGA used a 5-point response scale of: "never," "rarely," "sometimes," "often," or "always" with higher scores indicating a worse symptom rating.

    Measured: Baseline, Week 12

Timeline

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

  1. First posted12 Apr 2018
  2. Study start8 May 2018
  3. Primary completion13 Oct 2022
  4. Study completion13 Oct 2022

Why it stopped: Sponsor's decision

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
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
188 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03496623
Sponsor's protocol ID
RIN-PH-304
Acronym
PERFECT
Status last verified
Nov 2023
First submitted
29 Mar 2018
Last updated
24 Nov 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Nathan SD, Argula R, Trivieri MG, Aziz S, Gay E, Medarov B, Parambil J, Raina A, Risbano MG, Thenappan T, Soto JS, Bell H, Lacasse V, Sista P, Di Marino M, Smart A, Hawkes B, Nelson E, Bull T, Tapson V, Waxman A. Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results. Eur Respir J. 2024 Jun 6;63(6):2400172. doi: 10.1183/13993003.00172-2024. Print 2024 Jun.

    PubMed 38811045

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Inhaled treprostinil solution in people with Pulmonary Hypertension and Chronic Obstructive Pulmonary Disease, run by United Therapeutics at 76 sites in 4 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 18 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 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 sites in United States, Argentina, Israel, 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 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 24 Nov 2023). 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 From Baseline to Week 12 in 6-Minute Walk Distance (6MWD) (time frame: Baseline, Week 12). 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 NCT03496623, which also lists 1 linked publication.

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 24 Nov 2023.

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