A Study to Evaluate Whether Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

NCT03153111 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: AC-055G2022016-003653-15
• Study Type: interventional
• Target: 143
• Locations: 17 countries
• Sites: 95

Brief Summary

This is a study to evaluate whether macitentan is an effective and safe treatment for patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary vascular disease. The primary objective is to evaluate whether macitentan 10 mg reduces N-terminal pro-brain natriuretic peptide (NT-pro-BNP) as compared to placebo in these patients.

Conditions

Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Percent of Baseline N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Assessed at Week 24

  Percent of baseline NT-proBNP assessed at Week 24 was reported. Percent of baseline is calculated as the ratio of the Week 24 NT-proBNP value over baseline value, expressed in percentage. NT-proBNP is one of the best established cardiovascular response markers among all available surrogates in heart failure (HF).

  Week 24

Secondary Outcomes (3)

• Change From Baseline to Week 24 in the Clinical Summary Score Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) Score

  Baseline to Week 24

• Change From Baseline to Week 24 in Accelerometer-assessed Proportion of Time Spent in Light to Vigourous Physical Activity

  Baseline to Week 24

• Number of Participants With Worsening of Heart Failure (WHF) Events Over 52 Weeks

  Weeks 16, 24, 36, 52

Study Arms (2)

Macitentan

ACTIVE COMPARATOR

Subjects randomized to the macitentan arm receives one tablet of macitentan 10 mg every day for at least 24 to maximum 52 weeks.

Drug: Macitentan

Placebo

PLACEBO COMPARATOR

Subjects randomized to the placebo arm received one tablet of placebo every day for at least 24 to maximum 52 weeks.

Drug: Placebo

Interventions

Macitentan DRUG

macitentan 10 mg; film-coated tablet; oral use

Also known as: ACT-064992

Macitentan

Placebo DRUG

film-coated tablet (identical to the macitentan tablet); oral use

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signs or symptoms of Heart Failure (HF) (NYHA FC I I and II I ) requiring treatment with at least one oral diuretic (any type)
• Left ventricular ejection fraction (LVEF) ≥ 40% (by echocardiography at Screening)
• Structural heart disease consistent with heart failure with preserved ejection fraction (HFpEF) established by echocardiography at Screening
• Elevated NT-proBNP
• Pulmonary vascular disease or right ventricular dysfunction

You may not qualify if:

• Any prior valid measurement of LVEF \< 40%. An echocardiogram is considered valid if its quality is sufficient to allow accurate assessment of LVEF and if it is reflective of the true status of the subject
• Cardiovascular co-morbidities (e.g., significant unrepaired structural valvular heart disease; acute coronary syndrome, coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) within 3 months of Screening; uncontrolled heart rate from atrial fibrillation or atrial flutter, history of serious life-threatening or hemodynamically significant arrhythmia; history of or anticipated heart transplant or ventricular assist device implantation, etc)
• Systolic blood pressure (SBP) ≥ 180 mmHg, or diastolic blood pressure (DBP) ≥ 110 mmHg during Screening
• Hemoglobin \< 100g/L (\< 10 g/dl) at Screening
• Significant parenchymal lung disease (e.g., severe COPD, moderate or severe restrictive lung disease, diffuse interstitial fibrosis or alveolitis, pulmonary thromboembolism)
• Severe renal dysfunction with an estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min per 1.73 m2
• Severe hepatic impairment, e.g., Child Pugh Class C

Sponsors & Collaborators

• Actelion: lead

Study Sites (95)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Cedars Sinai Heart Institute

Beverly Hills, California, 90211, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Harbor Ucla Medical Center

Torrance, California, 90502, United States

Location

South Denver Cardiology Associates PC

Littleton, Colorado, 80120, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University Of Iowa - Hospitals & Clinics

Iowa City, Iowa, 52242-1081, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Peak Clinical Trials

Apex, North Carolina, 27502, United States

Location

University of North Carolina (UNC) - School of Medicine

Chapel Hill, North Carolina, 27599, United States

Location

The Lindner Clinical Trial Center

Cincinnati, Ohio, 45219-2906, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Allegheny

Pittsburgh, Pennsylvania, 15212, United States

Location

Vascular Medicine Institute University Of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

AnMed Health

Anderson, South Carolina, 29621, United States

Location

North Dallas Research Associates

McKinney, Texas, 75069, United States

Location

Baylor Scott and White Research Institute

Temple, Texas, 76508, United States

Location

Inova Heart and Vascular Institute

Falls Church, Virginia, 22042, United States

Location

MultiCare Health System

Tacoma, Washington, 98405, United States

Location

Aurora Saint Lukes Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Centro Médico Dra. De Salvo

Buenos Aires, C1426ABP, Argentina

Location

CCBR - Buenos Aires - AR

Buenos Aires, C1430CKE, Argentina

Location

Clinica Adventista Belgrano

CABA, C1430EGF, Argentina

Location

Instituto de Investigaciones Clinicas Mar del Plata

Mar del Plata, B7600FZN, Argentina

Location

Medizinische Universitaet Wien

Vienna, 1090, Austria

Location

Maestri E Kormann Consultoria Médico- Científica Ltda

Blumenau, 89020-430, Brazil

Location

Rede D or Sao Luiz S A Hospital do Coracao do Brasil

Brasília, 70390-700, Brazil

Location

Instituto de Pesquisa Clinica de Campinas

Campinas, 13060-080, Brazil

Location

Instituto do Coracao de Marília

Marília, 17515-000, Brazil

Location

Instituto de Moléstias Cardiovasculares Tatuí

Tatuí, 18270-170, Brazil

Location

Specialized Hospital for Active Treatment in Cardiology - Pleven

Pleven, 5800, Bulgaria

Location

Diagnostic Consulting Center I Sliven

Sliven, 8800, Bulgaria

Location

Multiprofile Hospital for Active Treatment - National Heart Hospital

Sofia, 1309, Bulgaria

Location

University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD

Sofia, 1750, Bulgaria

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

University Hospital Plzeň-Lochotín

Pilsen, 304 60, Czechia

Location

General University Hospital II.department of Internal Medicine-cardiology and angiology

Prague, 128 08, Czechia

Location

IKEM

Prague, 140 21, Czechia

Location

Aarhus Universitetshospital

Aarhus, 8200, Denmark

Location

Bispebjerg Og Frederiksberg Hospital

Copenhagen, 2400, Denmark

Location

Sydvestjysk Sygehus

Esbjerg, 6700, Denmark

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

CHU de Grenoble Hopital Albert Michallon

Grenoble, 38043, France

Location

Hopital de Bicetre

Le Kremlin-Bicêtre, 94270, France

Location

Hopital Cardiologique

Lille, 59037, France

Location

CHU Rouen Hopital Charles Nicolle

Rouen, 76031, France

Location

Charite Universitatsmedizin Berlin Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Universitatsklinikum Bonn

Bonn, 53105, Germany

Location

Herzzentrum Uniklinik Köln Klinik III für Innere Medizin

Cologne, 50937, Germany

Location

Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie

Dresden, 01307, Germany

Location

Universitaetsklinikum Giessen

Giessen, 35392, Germany

Location

Universitaetsklinikum Schleswig Holstein Campus Kiel

Kiel, 24105, Germany

Location

Klinikum Würzburg Mitte gGmbH Standort Missioklinik

Würzburg, 97074, Germany

Location

Budai Irgalmasrendi Korhaz

Budapest, 1023, Hungary

Location

Semmelweis Egyetem Varosmajor Sziv es Ergyogyaszati Klinika

Budapest, 1122, Hungary

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, 1134, Hungary

Location

Barzilai Medical Center

Ashkelon, Israel

Location

Hillel Yaffe Medical Center

Hadera, 3810101, Israel

Location

Bnai Zion Medical Center

Haifa, 3339419, Israel

Location

Wolfson Medical Center

Holon, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Galilee Medical Center

Nahariya, 2210001, Israel

Location

Rabin Medical Center Beilinson Campus

Petah Tikva, 4941492, Israel

Location

Kaplan Medical Center

Rehovot, 7610001, Israel

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 952, Poland

Location

Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn

Krakow, 31 202, Poland

Location

Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ

Lublin, 20 718, Poland

Location

4 Wojskowy Szpital Kliniczny Z Poliklinika SP ZOZ

Wroclaw, 50 513, Poland

Location

Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu

Bucharest, 022328, Romania

Location

Cardiomed

Craiova, 200505, Romania

Location

SAL MED Pitesti

Piteşti, 110437, Romania

Location

Cmi Dr Podoleanu Cristian

Târgu Mureş, 540503, Romania

Location

Federal State Budget Scientific Institution

Kemerovo, 650002, Russia

Location

Krasnodar Regional Clinical Hospital

Krasnodar, 350086, Russia

Location

Moscow City Clinical Hospital No.51

Moscow, 121309, Russia

Location

National Medical Research Center of Cardiology of MoH of Russian Federation

Moscow, 121552, Russia

Location

Federal State Budgetary Institution

Saint Petersburg, 197341, Russia

Location

State Healthcare Institution, Regional Clinical Cardiology Dispensary

Saratov, 410028, Russia

Location

State Autonomous Healthcare Institution Of Yaroslavl Region

Yaroslavl, 150003, Russia

Location

Ekaterinburg City Clinical Hospital #14

Yekaterinburg, 620039, Russia

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

Sahlgrenska Universitetsjukhuset

Gothenburg, 413 45, Sweden

Location

Royal Papworth Hospital NHS Foundation Trust

Cambridge, CB2 0AY, United Kingdom

Location

Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Sheffield, S10 2RX, United Kingdom

Location

Related Publications (1)

• Shah SJ, Bonderman D, Borlaug BA, Cleland JGF, Lack G, Lu W, Voors AA, Zannad F, Gladwin MT. Macitentan for Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Pulmonary Vascular Disease: Results of the SERENADE Randomized Clinical Trial and Open-Label Extension Study. Circ Heart Fail. 2025 Mar;18(3):e011381. doi: 10.1161/CIRCHEARTFAILURE.123.011381. Epub 2025 Mar 11.

  PMID: 40066571 DERIVED

MeSH Terms

Interventions

macitentan

Limitations and Caveats

Recruitment was stopped prematurely in December 2019 due to slow enrollment which resulted in an underpowered study and impacted the meaningful interpretation of the results.

Results Point of Contact

• Title: Clinical Scientific Leader
• Organization: Actelion

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: May 15, 2017
• Study Start: July 11, 2017
• Primary Completion: March 12, 2021
• Study Completion: March 12, 2021
• Last Updated: March 30, 2025
• Results First Posted: April 4, 2022

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); DE (7); PL (4); RU (8); BR (5); IL (8); BU (4); AR (4); ES (5); GB (4); HU (3); FR (5); CZ (5); RO (4); DK (3); US (24); SE (1)