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 (SERENADE)

April 28, 2023 updated by: Actelion

A Multi-center, Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of Macitentan in Subjects With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

143

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1430CKE
        • CCBR - Buenos Aires - AR
      • Caba, Argentina, C1430EGF
        • Clinica Adventista Belgrano
      • Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
        • Centro Médico Dra. De Salvo
      • Mar Del Plata, Argentina, B7600FZN
        • Instituto de Investigaciones Clinicas Mar del Plata
  • Austria
      • Vienna, Austria, 1090
        • Medizinische Universität Wien
  • Brazil
      • Blumenau, Brazil, 89020-430
        • Maestri E Kormann Consultoria Médico- Científica Ltda
      • Brasilia, Brazil, 70390-700
        • Rede D´or Sao Luiz S.A. - Hospital do Coracao do Brasil
      • Campinas, Brazil, 13060-080
        • Instituto de Pesquisa Clínica de Campinas
      • Marilia, Brazil, 17515-000
        • Instituto Do Coracao De Marilia
      • Tatuí, Brazil, 18270-170
        • Instituto de Moléstias Cardiovasculares Tatuí
  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Specialized Hospital for Active Treatment in Cardiology - Pleven
      • Sliven, Bulgaria, 8800
        • Diagnostic - Consulting Center I-Sliven
      • Sofia, Bulgaria, 1750
        • University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
      • Sofia, Bulgaria, 1309
        • Multiprofile Hospital for Active Treatment - National Heart Hospital
  • Czechia
      • Brno, Czechia, 625 00
        • Fakultní Nemocnice Brno
      • Hradec Králové, Czechia, 500 05
        • Fakultni nemocnice Hradec Kralove
      • Plzen, Czechia, 304 60
        • University Hospital Plzeň-Lochotín
      • Praha 2, Czechia, 128 08
        • General University Hospital II.department of Internal Medicine-cardiology and angiology
      • Praha 4, Czechia, 140 21
        • IKEM
  • Denmark
      • Aarhus, Denmark, 8200
        • Aarhus Universitetshospital
      • Copenhagen, Denmark, 2400
        • Bispebjerg og Frederiksberg Hospital
      • Esbjerg, Denmark, 6700
        • Sydvestjysk Sygehus
  • France
      • Creteil Cedex, France, 94010
        • Hôpital Henri Mondor
      • Grenoble Cedex 9, France, 38043
        • CHU de Grenoble - Hôpital Albert Michallon
      • Le Kremlin Bicetre, France, 94270
        • Hopital de Bicetre
      • Lille Cedex, France, 59037
        • Hopital Cardiologique
      • Rouen Cedex, France, 76031
        • CHU Rouen - Hôpital Charles Nicolle
  • Germany
      • Berlin, Germany, 13353
        • Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
      • Bonn, Germany, 53105
        • Universitätsklinikum Bonn
      • Dresden, Germany, 01307
        • Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie
      • Giessen, Germany, 35392
        • Universitaetsklinikum Giessen
      • Kiel, Germany, 24105
        • Universitaetsklinikum Schleswig-Holstein Campus Kiel
      • Köln, Germany, 50937
        • Herzzentrum Uniklinik Köln Klinik III für Innere Medizin
      • Würzburg, Germany, 97074
        • Klinikum Würzburg Mitte gGmbH Standort Missioklinik
  • Hungary
      • Budapest, Hungary, 1023
        • Budai Irgalmasrendi Korhaz
      • Budapest, Hungary, 1134
        • Magyar Honvedseg Egeszsegugyi Kozpont
      • Budapest, Hungary, 1122
        • Semmelweis Egyetem Városmajor Szív- és Érgyógyászati Klinika
  • Israel
      • Ashkelon, Israel
        • Barzilai Medical Center
      • Hadera, Israel, 3810101
        • Hillel Yaffe Medical Center
      • Haifa, Israel, 3339419
        • Bnai Zion Medical Center
      • Holon, Israel
        • Wolfson Medical Center
      • Jerusalem, Israel, 9112001
        • Hadassah Medical Center
      • Nahariya, Israel, 2210001
        • Galilee Medical Center
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center, Beilinson Campus
      • Rehovot, Israel, 7610001
        • Kaplan Medical Center
  • Poland
      • Gdansk, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne
      • Krakow, Poland, 31-202
        • Krakowski Szpital Specjalityczny im. Jana Pawla II, Oddzial Kliniczny Chorob Serca i Naczyn
      • Lublin, Poland, 20-718
        • Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ
      • Wroclaw, Poland, 50-513
        • 4 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ
  • Romania
      • Bucuresti, Romania, 022328
        • Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu Sectia cardiologie III
      • Craiova, Romania, 200505
        • Cardiomed
      • Pitesti, Romania, 110437
        • SAL MED Pitesti
      • Targu-Mures, Romania, 540503
        • Cmi Dr Podoleanu Cristian
  • Russian Federation
      • Ekaterinburg, Russian Federation, 620039
        • Ekaterinburg City Clinical Hospital #14
      • Kemerovo, Russian Federation, 650002
        • Federal State Budget Scientific Institution
      • Krasnodar, Russian Federation, 350086
        • Krasnodar Regional Clinical Hospital
      • Moscow, Russian Federation, 121552
        • National Medical Research Center of Cardiology of MoH of Russian Federation
      • Moscow, Russian Federation, 121309
        • Moscow City Clinical Hospital No.51
      • Saratov, Russian Federation, 410028
        • State Healthcare Institution, Regional Clinical Cardiology Dispensary
      • St Petersburg, Russian Federation, 197341
        • Federal State Budgetary Institution
      • Yaroslavl, Russian Federation, 150003
        • State Autonomous Healthcare Institution Of Yaroslavl Region
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Vall d'Hebron
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Maranon
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain, 46026
        • Hospital Universitario La Fe
  • Sweden
      • Goteborg, Sweden, 413 45
        • Sahlgrenska Universitetsjukhuset
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0AY
        • Royal Papworth Hospital NHS Foundation Trust
      • Cottingham, United Kingdom, HU16 5JQ
        • Castle Hill Hospital
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • Sheffield, United Kingdom, S10 2RX
        • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Arizona
    • California
      • Beverly Hills, California, United States, 90211
        • Cedars Sinai Heart Institute
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
      • Torrance, California, United States, 90502
        • Harbor Ucla Medical Center
    • Colorado
      • Littleton, Colorado, United States, 80120
        • South Denver Cardiology Associates PC
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine
    • Iowa
      • Iowa City, Iowa, United States, 52242-1081
        • University Of Iowa - Hospitals & Clinics
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10021
        • Weill Cornell Medicine
    • North Carolina
      • Apex, North Carolina, United States, 27502
        • Peak Clinical Trials
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina (UNC) - School of Medicine
    • Ohio
      • Cincinnati, Ohio, United States, 45219-2906
        • The Lindner Clinical Trial Center
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Health Network
      • Philadelphia, Pennsylvania, United States, 19102
        • Drexel University College of Medicine
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny
      • Pittsburgh, Pennsylvania, United States, 15261
        • Vascular Medicine Institute University Of Pittsburgh
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • AnMed Health
    • Texas
      • McKinney, Texas, United States, 75069
        • North Dallas Research Associates
      • Temple, Texas, United States, 76508
        • Baylor Scott & White Research Institute
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Heart and Vascular Institute
    • Washington
      • Tacoma, Washington, United States, 98405
        • Multicare Health System
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Saint Lukes Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Macitentan
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
macitentan 10 mg; film-coated tablet; oral use
Other Names:
  • ACT-064992
Placebo Comparator: Placebo
Subjects randomized to the placebo arm received one tablet of placebo every day for at least 24 to maximum 52 weeks.
Drug: Placebo
film-coated tablet (identical to the macitentan tablet); oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of Baseline N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Assessed at Week 24
Time Frame: 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 24 in the Clinical Summary Score Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) Score
Time Frame: Baseline to Week 24
The KCCQ is a validated health related quality of life measure for heart failure. The KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Clinical summary score is one of the quality of life variable of interest derived from KCCQ. Clinical summary score is the mean of domains: physical limitations score (6 items) and total symptom score (2 items [symptoms frequency and symptom burden]). The score is calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status.
Baseline to Week 24
Change From Baseline to Week 24 in Accelerometer-assessed Proportion of Time Spent in Light to Vigourous Physical Activity
Time Frame: Baseline to Week 24
Physical activity is assessed by accelerometer as the proportion of time spent in light to vigorous physical activity based on a threshold of greater than (>)100 activity counts per minute and expressed as change from baseline to Week 24.
Baseline to Week 24
Number of Participants With Worsening of Heart Failure (WHF) Events Over 52 Weeks
Time Frame: Weeks 16, 24, 36, 52
Number of participants with WHF events were reported. A WHF event includes HF death, hospitalization for WHF or an urgent visit for WHF.
Weeks 16, 24, 36, 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Actelion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 11, 2017

Primary Completion (Actual)

March 12, 2021

Study Completion (Actual)

March 12, 2021

Study Registration Dates

First Submitted

March 30, 2017

First Submitted That Met QC Criteria

May 12, 2017

First Posted (Actual)

May 15, 2017

Study Record Updates

Last Update Posted (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

April 28, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-055G202
  • 2016-003653-15 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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