AzTrials
AzTrials

PAHPhase 3NCT03626688

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients

A Phase 3 study testing Ralinepag in people with PAH and Pulmonary Hypertension, run by United Therapeutics at 209 sites in 33 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

Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ralinepag
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
687 participants
Where
209 sitesin 33 countries
Study dates
24 Jan 2019to 31 Dec 2025
Phase
Phase 3
Are there results?
None posted in the registry

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

  • At least 18 years of age.
  • Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
  • Primary diagnosis of symptomatic PAH.
  • Has had a right heart catheterization (RHC) performed at or within 3 years prior to Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH.
  • Has WHO/ NYHA functional class II to IV symptoms.
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  • If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator.
  • Has a 6MWD of ≥150 meters.
  • If taking concomitant medications that may affect the clinical manifestations of PAH (eg, calcium channel blockers, diuretics, digoxin, or L arginine supplementation, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of diuretics must be stable for at least the 10 days prior to Baseline.
  • Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through to the 30-Day Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process during the study and for 30 days after the last dose of IMP. Eligible male subjects must agree not to participate in sperm donation for 90 days after the last dose of IMP.

Who cannot join

  • For subjects with known HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Baseline.
  • Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.
  • Has evidence of more than mild lung disease on pulmonary function tests performed within 180 days prior to, or during Screening.
  • Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.
  • Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
  • Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec and female subjects with a QTcF >470 msec on ECG recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval greater than 110 msec, will be excluded if the QTcF is >500 msec for both males and females.
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  • Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).
  • Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
  • Subjects with alanine aminotransferase or aspartate aminotransferase ≥3 times the upper limit of normal (ULN) or total bilirubin ≥2 × ULN at Screening.
  • Chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL or requiring dialysis at Screening.
  • Hemoglobin concentration <9 g/dL at Screening.
  • Subjects treated with an IV or SC prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) or activin signaling inhibitor for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
  • Subjects currently on or who were treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) for >6 months or within 90 days prior to Baseline.
  • Subject has pulmonary veno-occlusive disease.
  • Malignancy diagnosed and/or treated within 5 years prior to Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.
  • Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine or phencyclidine in urine drug screen performed at Screening, or has a recent history (6 months) of alcohol or drug abuse. A subject will not be excluded due to a positive drug screen caused by prescribed medications.
  • Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
  • Prior participation in any study of ralinepag or participation in another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, as long as the subject can fulfill all other entry criteria and comply with all study procedures.
  • Any reason that, in the opinion of the Investigator or Medical Monitor, precludes the subject from participating in the study (eg, any previous or intercurrent medical condition) that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation.
  • Known hypersensitivity to ralinepag or any of the excipients.
  • Life expectancy <12 months based on the Investigator's opinion.
  • Women who are pregnant, lactating or breast-feeding.

Trial locations and contacts

209 sites in 33 countries.

209 sites in 33 countries

United States68 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87131

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Piedmont Healthcare Pulmonary and Critical Care Research

    Austell, Georgia, 30106

  • Ascension Texas Cardiovascular

    Austin, Texas, 78705

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Boston University Medical Center

    Boston, Massachusetts, 02118

  • University of Virginia Medical Center

    Charlottesville, Virginia, 22908

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • University of Cincinnati-Medical Science Building

    Cincinnati, Ohio, 45267

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Vermont Lung Center

    Colchester, Vermont, 05446

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • National Jewish Health

    Denver, Colorado, 80206

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Ascension Alexian Brothers

    Elk Grove Village, Illinois, 60007

  • University of Florida

    Gainesville, Florida, 32610

  • Spectrum Health Medical Group

    Grand Rapids, Michigan, 49546

  • East Carolina University

    Greenville, North Carolina, 27834

  • Memorial Hermann Hospital

    Houston, Texas, 77030

  • The Methodist Hospital Research Institute

    Houston, Texas, 77030

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

  • Community Health Network Cancer Center North

    Indianapolis, Indiana, 46250

  • St. Vincent Medical Group, Inc.

    Indianapolis, Indiana, 46260

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Statcare Pulmonary Consultants

    Knoxville, Tennessee, 37919

  • UCSD Health Sciences

    La Jolla, California, 92037

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California, 90024

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Keck Hospital of USC

    Los Angeles, California, 90033

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • VA Greater Los Angeles Healthcare System

    Los Angeles, California, 90073

  • Kentuckiana Pulmonary Research Center

    Louisville, Kentucky, 40202

  • University of Miami

    Miami, Florida, 33136

  • Medical College of Wisconsin/Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Winthrop Hospital

    Mineola, New York, 11501

  • Ochsner Medical Center

    New Orleans, Louisiana, 70121

  • NYU Langone Medical Center

    New York, New York, 10016

  • Weill-Cornell-New York Presbyterian Hospital

    New York, New York, 10021

  • Mount Sinai School of Medicine

    New York, New York, 10029

  • Sentara Cardiovascular Research Institute

    Norfolk, Virginia, 23507

  • Integris Baptist Medical Center

    Oklahoma City, Oklahoma, 73112

  • Nebraska Medical Center

    Omaha, Nebraska, 68198

  • University of California, Irvine

    Orange, California, 19103

  • Central Florida Pulmonary Group

    Orlando, Florida, 32803

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Temple University

    Philadelphia, Pennsylvania, 19140

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • Oregon Clinic-Pulmonary West

    Portland, Oregon, 97225

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Carilion Clinic Pulmonary and Sleep Medicine

    Roanoke, Virginia, 24014

  • University of Rochester

    Rochester, New York, 14642

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • SBPA Research LLC

    Santa Barbara, California, 93105

  • Chest Medicine Associates

    South Portland, Maine, 04106

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford Healthcare

    Stanford, California, 94305

  • LA Biomedical Research Institute Harbor-UCLA Medical Center

    Torrance, California, 90502

  • University of Arizona

    Tucson, Arizona, 85724

  • Cleveland Clinic Florida

    Weston, Florida, 33331

Other trials in United States

Argentina12 sites

  • Sanatorio de la Trinidad Mitre

    Buenos Aires, Buenos Aires, C1039AAO

  • Cardiologia Palmero

    Caba, Buenos Aires F.D., 1425

  • Hospital Italiano

    Ciudad Autonoma Buenos Aires, Buenos Aires, C1181ACH

  • Hospital Britanico de Buenos Aires

    Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, 1280

  • Fundacion Respirar

    Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, 1426

  • Fundacion Favaloro

    Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, C1093AAS

  • Hospital Privado Centro Medico de Cordoba S.A

    Córdoba, Córdoba Province, X5016KEH

  • Hospital Italiano de Cordoba

    Córdoba, X5004BAL

  • Instituto de Cardiologia de Corrientes

    Corrientes, Corrientes Province

  • Instituto de Investigaciones Clinicas Mar del Plata

    Mar del Plata, Buenos Aires, 7600

  • Sanatorio Parque

    Rosario, Santa Fe Province, 2000

  • Hospital PROVINCIAL "Dr. Jose Maria Cullen"

    Santa Fe, Santa Fe Province, 3000

Other trials in Argentina

Australia11 sites

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • The Prince Charles Hospital

    Chermside, Queensland, 4032

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • St Vincent's Hospital Melbourne

    Fitzroy, Victoria, 3065

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • Nepean Hospital

    Kingswood, New South Wales, 2751

  • Macquarie University

    Macquarie, New South Wales, 2109

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • Westmead Hospital

    Sydney, New South Wales, 2145

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

France11 sites

  • CHU Besançon - Hôpital Jean Minjoz

    Besançon, 25030

  • CHU de Brest - Hôpital de la Cavale Blanche

    Brest, 29609

  • CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel, Service de Pneumologie, 59 Boulevard Pinel

    Bron, Rhone, 69677

  • CHU de Grenoble - Hôpital Albert Michallon, Clinique de Cardiologie, Boulevrad de la Chantourne

    Grenoble, Isere, 38048

  • Groupement Hospitalier Sud - Hôpital Bicêtre

    Le Kremlin-Bicêtre, Val de Marne, 94275

  • CHRU de Lille - Hopital Cardiologique

    Lille, 59037

  • Hôpital Nord - CHU Marseille

    Marseille, 13015

  • CHU de Rouen - Hôpital Charles Nicolle

    Rouen, Seine Maritime, 76031

  • CHU de Saint-Etienne - Hopital Nord, Service de Medecine vasculaire et therapeutique, 81 Avenue A. Raimond

    Saint-Étienne-de-Montluc, Pays de la Loire Region, 42005

  • CHU de Strasbourg - Nouvel Hôpital Civil, Ctre de competence Hypertension Arterielle Pulmona, 1 place de l Hopital

    Strasbourg, Bas Rhin, 67091

  • CHU Nancy - Hôpital de Brabois Adultes, Pneumologie- Oncologie Médicale, Rue du Morvan

    Vandœuvre-lès-Nancy, Meurthe et Moselle, 54511

Other trials in France

Germany8 sites

  • Schwarzwald-Baar Klinikum

    Donaueschingen, 78166

  • Universitaetsklinikum Carl Gustav Carus TU Dresden

    Dresden, 01307

  • Universitätsmedizin Greifswald

    Greifswald, Mecklenburg-Vorpommern, 17475

  • Universitaetsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Thoraxklinik-Heidelberg Zentrum für Pulmonale Hypertonie

    Heidelberg, Baden-Wurttemberg, 69126

  • Universitaetsklinikum des Saarlandes, Innere Medizin V, IMED, Kirrberger Strasse 100, Gebäude 41

    Homburg, Saarland, 66424

  • Universitätsklinikum Leipzig, Medizinische Klinik II, Pneumologie

    Leipzig, Saxony, 04103

  • Universitaetsmedizin der Johannes-Gutenberg-Universitaet Mainz, Zentrum für Kardiologie I, Centrum für Thrombose und Hämostase (CTH), Langenbeckstrasse 1

    Mainz, Rhineland-Palatinate, 55131

Other trials in Germany

Brazil7 sites

  • Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa

    Belo Horizonte, Minas Gerais, 30441-070

  • UNESP-Faculdade de Medicina da Universidade Estadual Paulista Campus Botucatu

    Botucatu, São Paulo, 18618-687

  • HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás

    Goiânia, Goiás, 74605-020

  • Hospital Sao Lucas da PUC-RS

    Porto Alegre, R.S, 90610-000

  • Irmandade da Santa Casa de Misericórdia de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90035-074

  • Hospital Sao Paulo

    São Paulo, São Paulo, 04037-002

  • Instituto do Coracao

    São Paulo, São Paulo, 05403-000

Other trials in Brazil

Italy7 sites

  • Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia, S.C. di Cardiologia, Viale Luigi Pinto, 1

    Foggia, Foggia, 71100

  • IRCC Ospedale Policlinico San Martino

    Genova, Genova, 16132

  • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35

    Milan, 20122

  • Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)

    Monza, 20900

  • Istituto Mediterraneo Trapianti e Terapie a Alta Specializzazione (IRCCS-ISMETT)

    Palermo, PA, 90127

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, 27100

  • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza, Viale del Policlinico, 155

    Roma, Roma, 00161

Other trials in Italy

Turkey (Türkiye)7 sites

  • Balcalı, Çukurova Üniversitesi Kardiyoloji ABD

    Adana, Saricam, 01330

  • Gazi University Medical Faculty Hospital

    Ankara, 06560

  • Uludag Universitesi Tip Fakültesi, Gorukle Kampusu

    Bursa, 16059

  • Osmangazi Uni Medical Faculty

    Eskişehir, Odunpazari, 26040

  • Marmara Universitesi Istanbul Pendik Egitim ve Arastirma Hastanesi

    Istanbul, 34899

  • Dokuz Eylul Universitesi Tip Fakultesi, Mithatpasa caddesi Inciralti Balcova

    Izmir, 35340

  • Mersin Üniversitesi Tip Fakültesi Ciftlikköy Kampüsü

    Mersin, Yenisehir, 33343

Other trials in Turkey (Türkiye)

Canada5 sites

  • Peter Lougheed Centre

    Calgary, Alberta, T1Y 6J4

  • LHSC - Victoria Hospital

    London, Ontario, N6A 5W9

  • SMBD Jewish General Hospital d/b/a Jewish General Hospital

    Montreal, Quebec, H3T1E2

  • Institut Universitaire de Cardiologie et de Pneumologie de Quebec

    Québec, Quebec, G1V 4G5

  • University Health Network-Toronto General Hospital

    Toronto, Ontario, M5G 2N2

Other trials in Canada

China5 sites

  • Beijing Shijitan Hospital, Capital Medical University

    Beijing, Beijing Municipality, 100038

  • Fuwai Hospital, Chinese Academy of Medical Sciences

    Beijing, 100037

  • Xiangya Hospital Central South University

    Changsha, Hunan, 410008

  • Guangdong Provincial People's Hospital

    Guangzhou, Guangdong, 510080

  • Shanghai Pulmonary Hospital

    Shanghai, Shanghai Municipality, 200443

Other trials in China

Israel5 sites

  • The Lady Davis Carmel Medical Center, 7 Michal st.

    Haifa, 3436212

  • Hadassah Ein Kerem Medical Center, Kiryat Hadassah

    Jerusalem, 9112001

  • Meir Medical Center, 59 Tshernichovski st.

    Kfar Saba, 4428164

  • Rabin Medical Center-Beilinson Campus, Pulmonary Institute, 39 Jabotinsky St Ground floor

    Petah Tikva, 4941492

  • Tel Aviv Sourasky Medical Center, 6 Weizmann St.

    Tel Aviv, 6423906

Other trials in Israel

Poland5 sites

  • Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Kardiologii z Oddzialem Intensywnego Nazdoru Kardiologicznego, M. Sklodowskiej 24a

    Bialystok, 15-276

  • Krakowski Szpital Specjalistyczny im. Jana Pawla II, Oddział Kliniczny Chorób Serca i Naczyń z Pododdziałem Intensywnego Nadzoru Kardiologicznego, Pradnicka 80

    Krakow, 31-202

  • NZOZ Europejskie Centrum Zdrowia, ul. Borowa 14/18

    Otwock, 05-400

  • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu, Oddzial Kardiologii - F, ul. Dluga 1/2

    Poznan, 61-848

  • Premium Clinic Wrocław CM, Podwale 83/17

    Wroclaw, 50-414

Other trials in Poland

United Kingdom5 sites

  • Golden Jubilee National Hospital

    Glasgow, West Dunbartonshire, G81 4DY

  • Royal Free London NHS Foundation Trust, Pond Street

    London, Greater London, NW3 2QG

  • Royal Brompton Hospital

    London, SW3 6NP

  • Imperial College Healthcare NHS Trust

    London, W12 0HS

  • The Newcastle upon Tyne Hospitals NHS Foundation Trust, Sir William Leech Lung Research Centre

    Newcastle upon Tyne, Tyne and Wear, NE7 7DN

Other trials in United Kingdom

Greece4 sites

  • University General Hospital of Alexandroupolis

    Alexandroupoli, 68100

  • "Onasseio" Cardiosurgery Hospital, Hemodynamic Research and Interventional Cardiology Dept., 356, Syggrou Avenue

    Athens, Kallithea, 17674

  • University General Hospital Attikon

    Chaïdári, 12462

  • AHEPA General Hospital of Thessaloniki, A' Cardiology Clinic, 1 St. Kyriakidi Street

    Thessaloniki, 54636

Other trials in Greece

Mexico4 sites

  • CICUM San Miguel

    Guadalajara, Jalisco, 44160

  • Instituto Nacional de Cardiologia Dr Ignacio Chavez Rivera

    Mexico City, Mexico City, 14080

  • Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran

    Mexico City, Mexico City, 14080

  • Unidad de Investigacion Clinica en Medicina, S.C.

    Monterrey, N.L., 64718

Other trials in Mexico

Portugal4 sites

  • Hospital Garcia de Orta, E.P.E

    Almada, 2805-267

  • Centro Hospitalar e Universitário de Coimbra, E.P.E.

    Coimbra, 3000-075

  • Centro Hospitalar Universitário Lisboa Norte, E.P.E. Hospital Pulido Valente

    Lisbon, 1769-001

  • Centro Hospitalar de Santo António E.P.E.

    Porto, Porto District, 4099-001

Other trials in Portugal

Romania4 sites

  • Institutul de Urgenta pentru Boli Cardiovasculare "Prof. Dr. C.C. Iliescu", Sos. Fundeni nr. 258

    Bucharest, 022328

  • Institutul de Pneumoftiziologie "Marius Nasta", Sos. Viilor nr. 90, Sector 5

    Bucharest, 050159

  • Institutul Inimii "Niculae Stancioiu" Cluj-Napoca, Cardiologie, Str. Motilor nr. 19-21

    Cluj-Napoca, 400001

  • Spitalul Clinic de Boli Infectioase si Pneumoftiziologie "Dr. Victor Babes" Timisoara, Str. Gheorghe Adam nr. 13

    Timișoara, 300310

Other trials in Romania

Spain4 sites

  • Hospital Universitari Vall d'Hebron, Respiratory Dept., Passeig Vall d'Hebron,119-129, Neumologia

    Barcelona, 08035

  • Hospital Clinic de Barcelona, C/ Villarroel, 170

    Barcelona, 08036

  • Hospital Universitario 12 de Octubre

    Madrid, Madrid, 28041

  • Hospoital Universitari i Politecnic La Fe

    Valencia, Valencia, 46026

Other trials in Spain

Austria3 sites

  • Medizinische Universität Innsbruck

    Innsbruck, 6020

  • Ordensklinikum Linz GmbH - Elisabethinen, Fadingerstrasse 1

    Linz, 4020

  • AKH Wien, Innere Med. II, Kardiologie, Währingergürtel 18-20

    Vienna, 1090

Other trials in Austria

Hungary3 sites

  • Gottsegen György Országos Kardiovaszkuláris Intézet

    Budapest, Budapest, 1096

  • Pecsi Tudomanyegyetem, Szivgyogyaszati Klinika, Ifjusag u. 13.

    Pécs, 7624

  • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Családorvosi Intézet és Rendelő

    Szeged, Csongrád-Csanád, Hungary

Other trials in Hungary

Serbia3 sites

  • Clinical Center of Serbia, Koste Todorovica 8

    Belgrade, 11000

  • Clinical Center Zemun. Clinic for internal medicine, Department of Cardiology

    Belgrade, 11080

  • Institute for Pulmonary Diseases of Vojvodina, Put Dr Goldmana 4

    Kamenitz, 21204

Other trials in Serbia

South Korea3 sites

  • Gachon University Hospital Gil Medical Center

    Incheon, Namdong-gu, 21565

  • Samsung Medical Center

    Seoul, Gangnam-gu, 06351

  • Seoul National University Hospital

    Seoul, Jongno-gu, 03080

Other trials in South Korea

Sweden3 sites

  • Sahlgrenska Universitetssjukhuset

    Gothenburg, 41345

  • Linköping Universitetssjukhuset

    Linköping, 58185

  • Norrlands Universitetssjukhus, Hjärtcentrum

    Umeå, 90185

Other trials in Sweden

Ukraine3 sites

  • CE Dniprop RCC&C Center of Dniprop RC Dept of Card SI DMA of MOHU, Chair of Internal Medicine 3, 28, Knyazya Volodymyra Velykogo St.

    Dnipro, 49070

  • SI F.H.Yanovskyi National Institute of Phthisiology and Pulmonology of NAMSU, Clinical and Functional Dept, 10, Amosova St.

    Kyiv, 03680

  • Communal Noncommercial Enterprise of Lviv Regional Council Lviv Clinical Hospital, Dept of Cardiology, D.Halytskyi Lviv NMU, Ch of Internal Medicine #1, 7, Chernihivska str.

    Lviv, 79010

Other trials in Ukraine

Belgium2 sites

  • Cliniques Universitaires de Bruxelles Hopital Erasme

    Brussels, 1070

  • UZ Leuven, UZ Leuven Campus Gasthuisberg, Herestraat 49

    Leuven, 3000

Other trials in Belgium

Bulgaria2 sites

  • MHAT "Sveta Anna" Sofia AD

    Sofia, Sofia, 1750

  • MHAT - "National Heart Hospital" EAD, 65, Konyovitza Str.

    Sofia, 1309

Other trials in Bulgaria

Croatia2 sites

  • Clinical Hospital Dubrava Zagreb, Avenija G.Šuška 6

    Zagreb, 10000

  • University Clinic for Pulmonary Diseases, Jordanovac 104

    Zagreb, 10000

Other trials in Croatia

Denmark2 sites

  • Århus Universitetshospital

    Aarhus, 8200

  • Copenhagen University Hospital (Rigshospitalet)

    Copenhagen, 2100

Other trials in Denmark

Singapore2 sites

  • National University Hospital

    Singapore, Singapore, 119074

  • National Heart Centre

    Singapore, 169609

Other trials in Singapore

Taiwan2 sites

  • National Cheng Kung University Hospital

    Tainan, 704

  • National Taiwan University Hospital

    Taipei, Taipei, 10002

Other trials in Taiwan

Chile1 site

  • Instiuto Nacional del Torax

    Providencia, Santiago de Chile, 7500691

Other trials in Chile

Czechia1 site

  • Vseobecna fakultni nemocnice v Praze, II. interni klinika kardiologie a angiologie VFN a 1. LF UK, U nemocnice 2

    Prague, 128 08

Other trials in Czechia

Netherlands1 site

  • VU Medisch Centrum, De Boelelaan 1117

    Amsterdam, 1081 HV

Other trials in Netherlands

About this study

Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Ralinepag When Added to PAH Standard of Care or PAH Specific Background Therapy in Subjects With WHO Group 1 PAH

Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.

Read the detailed description

Study ROR-PH-301 is a multicenter, randomized, double-blind, placebo-controlled study. Subjects who meet entry criteria will be randomly allocated 1:1 to receive ralinepag or placebo, in addition to their standard of care or PAH-specific background therapy, as applicable. The primary endpoint is the time (in days) from randomization to the first adjudicated protocol-defined clinical worsening event. All primary endpoint events will be adjudicated by an independent Clinical Event Committee (CEC) in a blinded fashion. Subjects who have a confirmed primary endpoint event adjudicated by the CEC at any time during the study and all subjects on treatment at the conclusion of the study who have completed the Week 28 Visit (after the target number of confirmed events is achieved) will have the option to enroll in an open-label extension (OLE) study. Subjects who do not choose to participate in the OLE study will discontinue study drug and should remain in the study for long-term follow-up of survival status and will receive standard of care PAH treatment, at the discretion of the treating physician.

Being tested
Ralinepag, Placebo
Keywords
Prostacyclin, Connective Tissue Disease-Associated, 6 Minute Walk Test, 6 Minute Walk Distance, Pulmonary Vascular Resistance, Right Ventricular Function
Medical subject headings
Hypertension, Pulmonary, Pulmonary Arterial Hypertension, Hypertension, Connective Tissue Diseases, Familial Primary Pulmonary Hypertension, Vascular Diseases, Cardiovascular Diseases, Lung Diseases

What participants receive

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

  • RalinepagDrug

    Also called APD811

    Active

  • PlaceboDrug

    Placebo

Study groups in NCT03626688
Study groupRoleWhat they receive
RalinepagExperimentalRalinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the highest tolerated dose.
Receives: Drug: Ralinepag
PlaceboPlacebo comparatorMatching placebo tablets (oral)
Receives: Drug: Placebo

What is being measured

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

  1. Time from randomization to the first adjudicated protocol-defined clinical worsening event

    Clinical worsening events are defined as death, nonelective hospital admission for worsening PAH (further defined in clinical study protocol), initiation of parenteral or inhaled prostacyclin pathway agent for treatment of worsening PAH, disease progression (further defined in clinical study protocol), or unsatisfactory long-term clinical response (further defined in clinical study protocol).

    Measured: The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study, up to 3 years

Secondary outcomes (11)

  1. Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)

    NT-proBNP was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

    Measured: Baseline to Week 28

  2. Change from Baseline in 6-minute walk distance (6MWD)

    6MWD was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

    Measured: Baseline to Week 28

  3. Change from Baseline in WHO/New York Heart Association (NYHA) Functional Class

    The severity of PAH was graded according to the functional status of the subject and assessed at every visit.

    Measured: Baseline to Week 28

  4. Shift and proportion of subjects who attain all 3 of the following: NT-proBNP level <300 pg/mL, 6MWD >440 meters, and WHO/NYHA Functional Class I or II

    Data from NT-proBNP, 6MWD, and WHO/NYHA functional class assessment were compiled as a composite endpoint at visits through Week 28.

    Measured: Baseline to Week 28

  5. Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score

    Data from NT-proBNP, 6MWD, WHO/NYHA functional class, systolic blood pressure, heart rate, and estimated glomerular filtration rate values collected at visits through Week 28 were used to calculate the composite REVEAL risk score.

    Measured: Baseline to Week 28

  6. Clinical improvement as defined by the absence of clinical worsening and fulfillment of at least 2 of the 3 of the following: increase in 6MWD ≥10% or ≥30 m, improvement to or maintenance of WHO FC I or II, and decrease in NT-proBNP by at least 30%.

    Data from 6MWD, WHO/NYHA functional class assessment, and NT-proBNP were compiled as a composite endpoint at visits through Week 28.

    Measured: Baseline to Week 28

  7. Change from Baseline in health-related quality of life as measured by patient-reported outcomes.

    Quality of life was assessed using patient-reported outcomes at Baseline (prior to starting study drug) and Week 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

    Measured: Baseline to Week 28

  8. Time to first all-cause nonelective hospitalization

    All nonelective hopsitalizations during the study period were collected.

    Measured: The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study (when the target number of adjudicated events was achieved, as defined in the study protocol).

  9. Time to all-cause mortality

    All deaths during the study period were collected.

    Measured: The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study (when the target number of adjudicated events was achieved, as defined in the study protocol).

  10. Change from Baseline in heart rate recovery (HRR) following completion of the 6MWT

    HRR was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

    Measured: Baseline to Week 28

  11. Safety and tolerability of ralinepag in subjects with PAH

    Safety and tolerability were assessed by adverse events.

    Measured: Baseline to Week 28

Timeline

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

  1. First posted13 Aug 2018
  2. Study start24 Jan 2019
  3. Primary completion31 Dec 2025
  4. Study completion31 Dec 2025

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
687 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03626688
Sponsor's protocol ID
ROR-PH-301
Other IDs
APD811-301
Status last verified
Jun 2026
First submitted
27 Jul 2018
Last updated
16 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • McLaughlin VV, Solum D, Lachant D, Ataya A, Barbera JA, Meyer GB, Chang SA, Channick R, Church C, Feenstra J, Gaine S, Giannakoulas G, Jerjes-Sanchez C, Khanna D, Kim NH, Oudiz R, Preston IR, Sood N, Torres F, Vachiery JL, Pulido T, Cella D, Deng C, Escudero M, Lacasse V, Peterson L, Benza R, Humbert M; ADVANCE OUTCOMES Investigators. Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES): a randomised, double-blind, placebo-controlled phase 3 study. Lancet. 2026 Aug 8;408(10554):521-531. doi: 10.1016/S0140-6736(26)01011-1. Epub 2026 Jul 28.

    PubMed 42520828

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ralinepag in people with PAH and Pulmonary Hypertension, run by United Therapeutics at 209 sites in 33 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 10 inclusion and 22 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 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 209 sites in United States, Argentina, Australia, France, Germany and 28 more countries. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Time from randomization to the first adjudicated protocol-defined clinical worsening event (time frame: The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study, up to 3 years). 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 NCT03626688, 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 16 Jun 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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