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Pulmonary Arterial HypertensionPhase 3FREEDOM-EVNCT01560624

Phase III Clinical Worsening Study of UT-15C in Subjects With PAH Receiving Background Oral Monotherapy

A Phase 3 study testing Treprostinil Diolamine in people with Pulmonary Arterial Hypertension, run by United Therapeutics at 155 sites in 23 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 is an international, multicenter, randomized, double-blind, placebo-controlled, event driven study in subjects with pulmonary arterial hypertension. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
Treprostinil Diolamine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
690 participants
Where
155 sitesin 23 countries
Study dates
26 Jun 2012to 24 Jun 2018
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Subject Inclusion Criteria:

  1. Voluntarily gave informed consent to participate in the study.
  2. Are 18 to 75 years of age (inclusive) at Screening.
  3. Women of childbearing potential must practice abstinence from intercourse when in line with their preferred and usual lifestyle, or use 2 different forms of highly effective contraception for the duration of the study, and for at least 30 days after discontinuing study medication. A negative urine pregnancy test is required at Screening and Baseline prior to initiating study medication.
  4. Male subjects must consent to use a condom during intercourse for the duration of the study, and for at least 48 hours after discontinuing study medication.
  5. Have a diagnosis of symptomatic idiopathic or heritable PAH, PAH associated with connective tissue disease (CTD), PAH associated with HIV infection, PAH associated with repaired congenital systemic-to-pulmonary shunt, or PAH associated with appetite suppressant or toxin use.
  6. If known to be positive for HIV infection, have a CD4 lymphocyte count of at least 200 cells/mm^3 assessed at Screening and are receiving current standard of care anti retroviral or other effective medication for the treatment of HIV infection.
  7. Have a baseline 6MWD greater than or equal to 150 m in the absence of a concurrent injury, illness, or other confounding factor including, but not limited to, use of an aid for ambulation or connection to a nonportable machine, that would have prevented the accurate assessment of the subject's exercise capacity.
  8. Are optimally treated with conventional pulmonary hypertension therapy with no additions, discontinuations, or dose changes for a minimum of 10 days prior to randomization. The exceptions are the discontinuation or dose changes of anticoagulants and/or dose change of diuretics.
  9. Are receiving a PAH-approved oral monotherapy at a minimum dose that complies with the approved prescribing information for the product for at least 30 days prior to randomization and are receiving a stable dose for at least 10 days prior to randomization.
  10. Have had previously undergone a cardiac catheterization within 3 years prior to the start of Screening or during the Screening Period, and the most recent assessment documented a pulmonary artery pressure mean of at least 25 mmHg, a pulmonary capillary wedge pressure (PCWP) (or in the event a PCWP could not be reliably obtained, a left ventricular end diastolic pressure [LVEDP]) less than or equal to 15 mmHg, and absence of unrepaired congenital heart disease (other than patent foramen ovale). If a reliable PCWP or LVEDP are unable to be obtained during cardiac catheterization, subjects with clinically normal left heart function and absence of clinically relevant mitral valve disease on echocardiography are eligible for enrollment.
  11. Undergo echocardiography with evidence of clinically normal systolic and diastolic left ventricular function and absence of any clinically significant left sided heart disease (eg, mitral valve disease). Subjects with clinically insignificant left ventricular diastolic dysfunction due to the effects of right ventricular overload (ie, right ventricular hypertrophy and/or dilatation) are eligible.
  12. Have a previous ventilation perfusion lung scan, high-resolution computerized tomography scan of the chest, and/or pulmonary angiography that are consistent with the diagnosis of PAH.
  13. Have pulmonary function tests conducted within 6 months before Screening or during the Screening Period to confirm the following:
  14. Total lung capacity is at least 60%
  15. Forced expiratory volume at 1 second is at least 50%
  16. In the opinion of the Principal Investigator, is able to communicate effectively with study personnel and is considered reliable, willing, and likely to cooperate with protocol requirements, including attending all study visits.

Subject Exclusion Criteria:

  1. Is pregnant or lactating.
  2. Have previously received oral treprostinil.
  3. Have received a PGI2 (except if used during acute vasoreactivity testing) within 30 days prior to randomization or have previous intolerance or significant lack of efficacy to any PGI2 or PGI2 analogue that resulted in discontinuation or inability to titrate that therapy effectively.
  4. Have any background conventional therapies for PAH added, removed, or dose-adjusted within 10 days prior to randomization. The exceptions are removal or dose adjustments of anticoagulants and/or dose adjustments of diuretics.
  5. Receive their first dose of a PAH-approved oral monotherapy less than 30 days prior to randomization, or have their PAH-approved oral monotherapy dose changed within 10 days prior to randomization, or the subject discontinues any PAH approved therapy within 30 days prior to Screening, or the subject has previously received 2 PAH approved oral therapies at the same time (specifically, a PDE5-I, an ERA, or a sGC stimulator) concomitantly for more than 90 days cumulatively.
  6. Have any disease associated with PAH other than CTD, HIV infection, repaired (for at least 1 year) congenital systemic-to-pulmonary shunt, PAH associated with appetite suppressant/toxin use, or have an atrial septostomy.
  7. Have a current diagnosis of uncontrolled sleep apnea as defined by their physician.
  8. Have a history of ischemic heart disease, including a previous myocardial infarction or symptomatic coronary artery disease within 6 months prior to Screening or a history of left-sided myocardial disease as evidenced by a mean PCWP (or a LVEDP) greater than 15 mmHg or left ventricular ejection fraction less than 40% as assessed by either multigated angiogram, angiography, or echocardiography.
  9. Have uncontrolled systemic hypertension as evidenced by systolic blood pressure (BP) greater than 160 mmHg or diastolic BP greater than 100 mmHg.
  10. Have alanine aminotransferase or aspartate aminotransferase levels at least 3 times greater than the upper limit of normal, clinically significant liver disease/dysfunction, or known Child-Pugh Class C hepatic disease at Screening.
  11. Have any other disease or condition that would interfere with the interpretation of study assessments.
  12. Have a musculoskeletal disorder, is using a device to assist walking, or any disease that is likely to limit ambulation, or is connected to a machine that is nonportable.
  13. Have an unstable psychiatric condition or is mentally incapable of understanding the objectives, nature, or consequences of the study, or has any condition which in the Investigator's opinion would constitute an unacceptable risk to the subject's safety.
  14. Is receiving an investigational drug, have an investigational device in place, or have participated in an investigational drug or device study within 30 days prior to Screening.
  15. Have chronic renal insufficiency as defined by either a Screening creatinine value greater than 2.5 mg/dL or the requirement for dialysis.
  16. Does not have 3 or more of the following left ventricular disease/dysfunction risk factors:
  17. Body mass index at least 30 kg/m^2
  18. History of essential hypertension
  19. Diabetes mellitus (any type)
  20. Historical evidence of significant coronary artery disease established by any 1 of the following: history of myocardial infarction, percutaneous coronary intervention, or angiographic evidence of coronary artery disease; positive stress test with imaging; previous coronary artery bypass graft; or stable angina.

Trial locations and contacts

155 sites in 23 countries.

155 sites in 23 countries

United States40 sites

  • Asheville Cardiology Associates

    Asheville, North Carolina, 28803

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Augusta University

    Augusta, Georgia, 30912

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Piedmont - Georgia Lung Associates

    Austell, Georgia, 30106

  • University of Maryland

    Baltimore, Maryland, 21201

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Indiana University Hospital

    Carmel, Indiana, 46032

  • University of Cincinnati

    Cincinnati, Ohio, 45267-0564

  • University Hospital

    Cleveland, Ohio, 44106

  • The Ohio State University

    Columbus, Ohio, 43321

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • University of California, San Francisco-Fresno

    Fresno, California, 93721

  • University of Florida

    Gainesville, Florida, 32610

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 55242

  • University of Florida College of Medicine Jacksonville- Division of Pulmonary & Critical Medicine

    Jacksonville, Florida, 32209

  • University of Florida College of Medicine Jacksonville

    Jacksonville, Florida, 32209

  • University of Florida College of Medicine, Jacksonville

    Jacksonville, Florida, 32209

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90211

  • Kentuckiana Pulmonary Associates

    Louisville, Kentucky, 40202

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Sentara Cardiovascular Research Institute

    Norfolk, Virginia, 23507

  • Nebraska Medical Center

    Omaha, Nebraska, 68198-5990

  • HeartCare Midwest

    Peoria, Illinois, 61614

  • Perelman Center for Advanced Medicine; University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Arizona Pulmonary Specialists, Ltd.

    Phoenix, Arizona, 85012

  • University of Pittsburgh Medical Center - Presbyterian Cardiovascular Institute

    Pittsburgh, Pennsylvania, 15213

  • Oregon Health and Science University

    Portland, Oregon, 97201-3098

  • Legacy Research Institute

    Portland, Oregon, 97210

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • University of Rochester

    Rochester, New York, 14642

  • University of California-Davis Medical Group, Advanced Lung Disease/Transplant Program

    Sacramento, California, 95817

  • David Geffen School of Medicine

    Torrance, California, 90502

  • Beaumont Health

    Troy, Michigan, 48085

  • University of Arizona

    Tucson, Arizona, 85724

  • Cleveland Clinic Florida

    Weston, Florida, 33331

Other trials in United States

China16 sites

  • Beijing Chao-Yang Hospital

    Beijing, Beijing Municipality, 100020

  • Peking Union Medical College Hospital

    Beijing, 100005

  • Beijing Shijitan Hospital

    Beijing, 100038

  • Chinese PLA General Hospital

    Beijing, 100853

  • Xiangya Hospital

    Changsha, Hunan, 410008

  • West China Hospital

    Chengdu, Sichuan, 610047

  • Guangdong General Hospital

    Guangzhou, Guangdong, 510080

  • The Second Affiliated Hospital of Nanchang Medical University

    Nanchang, Jiangxi, 330006

  • The First Affiliated Hospital of Nanjing Medical University

    Nanjing, Jiangsu, 210029

  • The Affiliated Hospital of Qingdao University

    Qingdao, 26603

  • Zhongshan Hospital Fudan University

    Shanghai, Shanghai Municipality, 200032

  • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

    Shanghai, Shanghai Municipality, 200120

  • Renji Hospital of Shanghai Jiaotong University

    Shanghai, 200001

  • Shanghai Pulmonary Hospital of Tongji University

    Shanghai, 200433

  • Shenyang General Hospital of Shenyang Military Command

    Shenyang, 110015

  • Wuhan Asia Heart Hospital

    Wuhan, Hubei, 430022

Other trials in China

Germany14 sites

  • Bergmannsheil Berufsgenossenschaftliche Universitätsklinik GmbH

    Bochum, North Rhine-Westphalia, 44789

  • Universitätsklinikum Köln

    Cologne, North Rhine-Westphalia, 50937

  • Technische Universität Dresden

    Dresden, Saxony, 01307

  • Herzzentrum Duisburg

    Duisburg, North Rhine-Westphalia, 47137

  • Universitätsmedizin Greifswald

    Greifswald, Mecklenburg-Vorpommern, 17475

  • Universitätskrankenhaus Hamburg-Eppendorf

    Hamburg, 20246

  • Thoraxklinik am Universitätsklinikum Heidelberg

    Heidelberg, Baden-Wurttemberg, 69126

  • Universitätsklinikum des Saarlandes

    Homburg, Saarland, 66424

  • Universitätsklinikum Leipzig

    Leipzig, Saxony, 04103

  • Universitätsmedizin der Johannes Gutenberg Universität

    Mainz, Rhineland-Palatinate, 55131

  • Ludwig-Maximilians-Universitat Munchen

    München, Bavaria, 81377

  • Universitätsklinikum Regensburg

    Regensburg, Bavaria, 93053

  • Technische Universität Dresden

    Sachsen, 01307

  • Missionsarztliche Klinik Wurzburg gGmbH

    Würzburg, Bavaria, 97074

Other trials in Germany

India12 sites

  • Care Institute Medical Sciences

    Ahmedabad, Gujarat, 38006

  • Narayana Institute of Cardiac Sciences

    Bangalore, Karnataka, 560 099

  • Apollo Hospital

    Chennai, Tamil Nadu, 600006

  • G. Kuppuswamy Naidu Memorial Hospital

    Coimbatore, Tamil Nadu, 641037

  • Apollo Hospitals International, Ltd.

    Gandhinagar, Gujarat, 382428

  • Medanta - The Medicity

    Gurgaon, Haryana, 122 001

  • CARE Hospital

    Hyderabad, Andhra Pradesh, 500 001

  • Mediciti Hospital

    Hyderabad, Andhra Pradesh, 500 063

  • KEM Hospital

    Mumbai, Maharashtra, 400012

  • Sir Ganga Ram Hospital

    New Delhi, National Capital Territory of Delhi, 110060

  • Indraprastha Apollo Hospital

    New Delhi, National Capital Territory of Delhi, 110076

  • Ruby Hall Clinic

    Pune, Maharashtra, 411 001

Other trials in India

Australia8 sites

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • Prince Charles Hospital

    Chermside, Queensland, 4032

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • Nepean Hospital

    Kingswood, New South Wales, 2751

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • Royal Melbourne Hospital

    Parkville, Victoria, 3052

  • Saint Vincents Hospital

    Sydney, New South Wales, 2010

  • Macquarie University

    Sydney, New South Wales, 2109

Other trials in Australia

Brazil8 sites

  • Hospital das Clínicas da Universidade Federal de Minas Gerais

    Belo Horizonte, Minas Gerais, 30130-100

  • Hospital Madre Teresa

    Belo Horizonte, Minas Gerais, 30380-090

  • Hospital das Clínicas da Faculdade de Medicina de Botucatu- UNESP

    Botucatu, São Paulo, 18618-970

  • Hospital das Clinicas da Universidade Federal de Goias

    Goiânia, Goiás, 74605-050

  • Complexo Hospitalar Santa Casa de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90020-090

  • Hospital da Clínicas da Faculdade de Medicina da Universidade de São Paulo

    São Paulo, São Paulo, 05403-000

  • Escola Paulista de Medicina, Universidade Federal de São Paulo

    São Paulo, São Paulo

  • Hospital Alemão Oswaldo Cruz

    São Paulo, 01323-020

Other trials in Brazil

France6 sites

  • Hopital Jean Minjoz Centre Hospitalier Universitaire Besancon

    Besançon, Franche-comte, 25030

  • Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez

    Lille, Hauts-de-France, 59037

  • Centre Hospitalier Universitaire Hopital Nord

    Marseille, Provence-Alpes-Côte d'Azur Region, 13015

  • CHU de Montpellier

    Montpellier, Languedoc-roussillon, 34295

  • Hopital Haut-Leveque, CHU Bordeaux

    Pessac, Aquitaine, 33064

  • Hopital Brabois

    Vandœuvre-lès-Nancy, Limousin, Lorraine, 54500

Other trials in France

Argentina5 sites

  • Hospital Italiano de Buenos Aires

    Buenos Aires, Distrito Federal, C1181ACH

  • Sanatorio de la Trinidad Mitre

    Buenos Aires

  • Sanatorio San José

    CABA, Buenos Aires, C1425DUH

  • Hospital Italiano Garibaldi

    Rosario, Santa Fe Province, S2001OAD

  • Hospital Dr. José María Cullen

    Santa Fe, S3000EOY

Other trials in Argentina

Israel5 sites

  • Rambam Health Corp.

    Haifa, 31096

  • Carmel Medical Center

    Haifa, 34362

  • Hadassah Medical Center

    Jerusalem, 91120

  • Rabin Medical Center

    Petach Tikvah, Petah Tiqwa, 49100

  • The Chaim Sheba Medical Center at Tel Hashomer

    Tel HaShomer, Tel Aviv, 52621

Other trials in Israel

South Korea5 sites

  • Gachon University Gil Medical Center

    Incheon, 405-760

  • Seoul National University Hospital

    Seoul, 110-744

  • Severance Hospital, Yonsei University Health System

    Seoul, 120-752

  • Samsung Medical Center

    Seoul, 135-710

  • Asan Medical Center

    Seoul, 138-736

Other trials in South Korea

Canada4 sites

  • Respiratory Research Foundation

    Calgary, Alberta, T1Y 6J4

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • Lawson Health Research Institute

    London, Ontario, N6A 5A5

  • Vancouver Coastal Health

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

Italy4 sites

  • Azienda Ospedaliera Universitaria

    Naples

  • Istituto Mediterraneo Trapianti e Terapia Alta Specializzazione (ISMETT)

    Palermo, 90127

  • Fondazione IRCCS Policlinico S. Matteo

    Pavia, 27100

  • Azienda Policlinico Umberto I di Roma

    Roma, 00161

Other trials in Italy

Poland4 sites

  • Uniwersytecki Szpital Kliniczny w Bialymstoku

    Bialystok, 15276

  • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K. Marcinkowskiego w Poznaniu

    Krakow, 61848

  • Krakowski Szpital Specjalistyczny im. Jana Pawla II

    Małogoskie, 31202

  • Europejskie Centrum Zdrowia Otwock, Szpital im. Fryderyka Chopina

    Otwock

Other trials in Poland

Taiwan4 sites

  • Veterans General Hospital-Kaohsiung

    Kaohsiung City, 81362

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Cheng Kung University Hospital

    Tainan, Tainan CITY, 70403

  • National Taiwan University Hospital

    Taipei, 10002

Other trials in Taiwan

United Kingdom4 sites

  • Royal Free Hospital

    London, England, NW3 2QG

  • Freeman Hospital

    Newcastle upon Tyne, England, NE7 7DN

  • Papworth Hospital

    Papworth Everard, Cambridgshire, CB3 8RE

  • Royal Hallamshire Hospital

    Sheffield, England, S10 2JF

Other trials in United Kingdom

Austria2 sites

  • Krankenhaus Elisabethinen Linz

    Linz, Upper Austria, 4020

  • Medizinische Universität Wien

    Vienna, 1090

Other trials in Austria

Chile2 sites

  • Centro de Investigaciones TASOL

    Santiago, Santiago Metropolitan, 7500710

  • Clínica Tabancura

    Vitacura, Santiago Metropolitan, 7650018

Other trials in Chile

Denmark2 sites

  • Aarhus Universitetshospital, Skejby

    Aarhus, 8200

  • Rigshospitalet-Copenhagen University Hospital

    Copenhagen, 2100

Other trials in Denmark

Greece2 sites

  • University General Hospital of Attikon

    Athens, Attica, 12462

  • General Hospital of Thessaloniki, "G.Papanikolaou"

    Thessaloniki, Macedoni, 57010

Other trials in Greece

Mexico2 sites

  • Unidad de Investigacion Clinica en Medicina S.C.

    Monterrey, Nuevo León, 64718

  • Instituto Nacional de Cardiologia Ignacio Chavez

    Tlalpan, Mexico City, 14080

Other trials in Mexico

Netherlands2 sites

  • Vrije Universiteit Medisch Centrum

    Amsterdam, North Holland, 1081 HV

  • Universitair Medisch Centrum Sint Radboud

    Nijmegen, Gelderland, 6525 GA

Other trials in Netherlands

Singapore2 sites

  • National University Hospital

    Singapore, 119228

  • National Heart Centre Singapore

    Singapore, 168 752

Other trials in Singapore

Sweden2 sites

  • Sahlgrenska University Hospital

    Gothenburg, Västra Götaland County, 413 45

  • Karolinska University Hospital Solna

    Stockholm, 171 76

Other trials in Sweden

About this study

Official title: A Phase III, International, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Clinical Worsening Study of UT-15C in Subjects With Pulmonary Arterial Hypertension Receiving Background Oral Monotherapy

This is an international, multicenter, randomized, double-blind, placebo-controlled, event driven study in subjects with pulmonary arterial hypertension.

Read the detailed description

Study TDE-PH-310 is an international, multicenter, randomized (1:1 oral treprostinil (UT-15C): placebo), double-blind, placebo-controlled study in subjects with pulmonary arterial hypertension (PAH) who are receiving background oral monotherapy for PAH for at least 30 days at randomization. Subjects are randomly allocated to receive oral treprostinil extended-release tablets or placebo by a stratified randomization by type of background therapy (Strata 1: phosphodiesterase type 5 inhibitor [PDE5-I] or soluble guanylate cyclase [sGC] stimulator; Strata 2: endothelin receptor antagonist [ERA]. Subjects are also stratified by baseline 6-minute walk distance (6MWD) less than or equal to 350 m or greater than 350 m. Subjects receive their first dose of study drug (0.125 mg) or matching placebo on the day of randomization. Oral dosing of study drug is continued at 0.125 mg 3 times daily (TID; every 6 to 8 hours) with food. The dose (or matching placebo) is titrated throughout the study up to a maximum dose of 12 mg TID to reach and maintain a tolerated dosing regimen that provided optimal clinical benefit. Once randomized, subjects return for study visits every 4 weeks for the first 12 weeks, then every 12 weeks for the duration of the study. Subjects continue in the study until experiencing clinical worsening, the number of adjudicated events necessary for study closure occurr, or prematurely discontinue participation in the study for any reason other than protocol-specified clinical worsening. At each scheduled visit, subjects undergo efficacy assessments for clinical worsening, exercise capacity (6MWD and Borg dyspnea score), WHO functional class (FC), and plasma N-Terminal pro-brain natriuretic peptide (NT-proBNP). Subjects could participate in an optional hemodynamic sub-study (assessed by RHC). Safety assessments consist of adverse events (AEs), physical examinations, vital signs, 12-lead electrocardiograms (ECGs), and clinical laboratory parameters. Patients who complete all required assessments are eligible to enter a long-term, open-label, extension study (TDE-PH-311).

Being tested
Treprostinil Diolamine, Placebo
Keywords
Pulmonary arterial hypertension (PAH), Pulmonary hypertension (PH), Clinical Worsening, Freedom, Freedom-EV, Treprostinil, UT-15C, 6 Minute walk test
Medical subject headings
Pulmonary Arterial Hypertension, Hypertension, Pulmonary

What participants receive

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

  • Treprostinil DiolamineDrug

    Also called UT--15C

    Active

  • PlaceboDrug

    Placebo

Study groups in NCT01560624
Study groupRoleWhat they receive
UT-15CExperimentalTreprostinil diolamine extended-release tablets (oral) 0.125 to 12 mg TID
Receives: Drug: Treprostinil Diolamine
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 to First Clinical Worsening Event

    Clinical worsening was assessed continuously from randomization until the subject's last study visit. Clinical worsening events were defined as death (all causes), hospitalizations due to worsening pulmonary arterial hypertension (PAH), initiation of an inhaled or infused prostacyclin (PGI2) for the treatment of worsening PAH, disease progression, or unsatisfactory long-term clinical response. All clinical worsening events reported by the study sites were reviewed by the Sponsor Medical Monitors. Once a clinical worsening event occurred, it was entered in the eCRF and a narrative was submitted for review by the Sponsor's Medical Monitor within 48 hours after the event became known to the Investigator or designee. Subsequently, the narratives for subjects with the reported clinical worsening events were sent to an independent adjudication committee. The independent adjudication committee reviewed and adjudicated all clinical worsening events throughout the study.

    Measured: From randomization to approximately 4 years

Secondary outcomes (3)

  1. Change in 6-Minute Walk Distance

    The intent of the 6-Minute Walk Test (6MWT) is to evaluate exercise capacity associated with carrying out activities of daily living. A baseline 6MWT was performed prior to initiation of study drug on the day of randomization. 6MWTs were conducted at Weeks 4, 8, 12, 24, and every 12 weeks thereafter. The change between Baseline and Week 24 is reported.

    Measured: From Baseline to Week 24

  2. Change in Plasma N-Terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 24

    Plasma NT-proBNP concentration is a useful biomarker for the severity of PAH as it is associated with changes in right heart morphology and function. NT-proBNP sample collection occurred at Baseline (prior to starting study drug), Week 12, Week 24, the first Continued Visit, and every other Continued Visit thereafter (ie, Continued Visits 3, 5, 7, etc). NT-proBNP was also assessed at the Study Drug Termination Visit. The change between Baseline and Week 24 is reported.

    Measured: From Baseline to Week 24

  3. Change in World Health Organization Functional Class (WHO FC) From Baseline to Week 48

    The WHO FC for PAH was assessed at Baseline prior to starting study drug, at all subsequent scheduled study visits, and every time the 6MWT was performed for purposes of assessing clinical worsening status.

    Measured: Baseline to Week 48

Timeline

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

  1. First posted22 Mar 2012 (estimated)
  2. Study start26 Jun 2012
  3. Primary completion24 Jun 2018
  4. Study completion24 Jun 2018

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
690 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01560624
Sponsor's protocol ID
TDE-PH-310
Acronym
FREEDOM-EV
Status last verified
Feb 2020
First submitted
9 Mar 2012
Last updated
13 Feb 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • White RJ, Jerjes-Sanchez C, Bohns Meyer GM, Pulido T, Sepulveda P, Wang KY, Grunig E, Hiremath S, Yu Z, Gangcheng Z, Yip WLJ, Zhang S, Khan A, Deng CQ, Grover R, Tapson VF; FREEDOM-EV Investigators. Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial. Am J Respir Crit Care Med. 2020 Mar 15;201(6):707-717. doi: 10.1164/rccm.201908-1640OC.

    PubMed 31765604

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Treprostinil Diolamine in people with Pulmonary Arterial Hypertension, run by United Therapeutics at 155 sites in 23 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 13 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 155 sites in United States, China, Germany, India, Australia and 18 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?

Yes. Results are posted in the registry (first posted 13 Feb 2020). 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?

Time to First Clinical Worsening Event (time frame: From randomization to approximately 4 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 NCT01560624, 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 13 Feb 2020.

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