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

Heart Failure With Preserved Ejection Fraction Clinical Trial

— SERENADE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03153111
• Other study ID #: AC-055G202
• Secondary ID: 2016-003653-15
• Status: Completed
• Phase: Phase 2
• Start date: July 11, 2017
• Est. completion date: March 12, 2021

Study information

• Verified date: April 2023
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: March 12, 2021
• Est. primary completion date: March 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Vascular Diseases

Intervention

Drug:
• Macitentan
macitentan 10 mg; film-coated tablet; oral use
• Placebo
film-coated tablet (identical to the macitentan tablet); oral use

Locations

Country	Name	City	State
Argentina	CCBR - Buenos Aires - AR	Buenos Aires
Argentina	Clínica Adventista Belgrano	Caba
Argentina	Centro Médico Dra. De Salvo	Ciudad Autónoma de Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Mar del Plata	Mar Del Plata
Austria	Medizinische Universität Wien	Vienna
Brazil	Maestri E Kormann Consultoria Médico- Científica Ltda	Blumenau
Brazil	Rede D´or Sao Luiz S.A. - Hospital do Coracao do Brasil	Brasilia
Brazil	Instituto de Pesquisa Clinica de Campinas	Campinas
Brazil	Instituto do Coracao de Marília	Marilia
Brazil	Instituto de Moléstias Cardiovasculares Tatuí	Tatuí
Bulgaria	Specialized Hospital for Active Treatment in Cardiology - Pleven	Pleven
Bulgaria	Diagnostic - Consulting Center I-Sliven	Sliven
Bulgaria	Multiprofile Hospital for Active Treatment - National Heart Hospital	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD	Sofia
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	University Hospital Plzen-Lochotín	Plzen
Czechia	General University Hospital II.department of Internal Medicine-cardiology and angiology	Praha 2
Czechia	IKEM	Praha 4
Denmark	Aarhus Universitetshospital	Aarhus
Denmark	Bispebjerg Og Frederiksberg Hospital	Copenhagen
Denmark	Sydvestjysk Sygehus	Esbjerg
France	Hopital Henri Mondor	Creteil Cedex
France	CHU de Grenoble - Hopital Albert Michallon	Grenoble Cedex 9
France	Hopital de Bicetre	Le Kremlin Bicetre
France	Hopital Cardiologique	Lille Cedex
France	CHU Rouen - Hopital Charles Nicolle	Rouen Cedex
Germany	Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum	Berlin
Germany	Universitatsklinikum Bonn	Bonn
Germany	Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie	Dresden
Germany	Universitaetsklinikum Giessen	Giessen
Germany	Universitaetsklinikum Schleswig-Holstein Campus Kiel	Kiel
Germany	Herzzentrum Uniklinik Köln Klinik III für Innere Medizin	Köln
Germany	Klinikum Würzburg Mitte gGmbH Standort Missioklinik	Würzburg
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	Semmelweis Egyetem Városmajor Szív- és Érgyógyászati Klinika	Budapest
Israel	Barzilai Medical Center	Ashkelon
Israel	Hillel Yaffe Medical Center	Hadera
Israel	Bnai Zion Medical Center	Haifa
Israel	Wolfson Medical Center	Holon
Israel	Hadassah Medical Center	Jerusalem
Israel	Galilee Medical Center	Nahariya
Israel	Rabin Medical Center, Beilinson Campus	Petah Tikva
Israel	Kaplan Medical Center	Rehovot
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Krakowski Szpital Specjalityczny im. Jana Pawla II, Oddzial Kliniczny Chorob Serca i Naczyn	Krakow
Poland	Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ	Lublin
Poland	4 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ	Wroclaw
Romania	Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu Sectia cardiologie III	Bucuresti
Romania	Cardiomed	Craiova
Romania	SAL MED Pitesti	Pitesti
Romania	Cmi Dr Podoleanu Cristian	Targu-Mures
Russian Federation	Ekaterinburg City Clinical Hospital #14	Ekaterinburg
Russian Federation	Federal State Budget Scientific Institution	Kemerovo
Russian Federation	Krasnodar Regional Clinical Hospital	Krasnodar
Russian Federation	Moscow City Clinical Hospital No.51	Moscow
Russian Federation	National Medical Research Center of Cardiology of MoH of Russian Federation	Moscow
Russian Federation	State Healthcare Institution, Regional Clinical Cardiology Dispensary	Saratov
Russian Federation	Federal State Budgetary Institution	St Petersburg
Russian Federation	State Autonomous Healthcare Institution Of Yaroslavl Region	Yaroslavl
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario La Fe	Valencia
Sweden	Sahlgrenska Universitetsjukhuset	Goteborg
United Kingdom	Royal Papworth Hospital NHS Foundation Trust	Cambridge
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	Royal Free Hospital	London
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital	Sheffield
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	AnMed Health	Anderson	South Carolina
United States	Peak Clinical Trials	Apex	North Carolina
United States	University of Maryland	Baltimore	Maryland
United States	Cedars Sinai Heart Institute	Beverly Hills	California
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina (UNC) - School of Medicine	Chapel Hill	North Carolina
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	The Lindner Clinical Trial Center	Cincinnati	Ohio
United States	Inova Heart and Vascular Institute	Falls Church	Virginia
United States	University Of Iowa - Hospitals & Clinics	Iowa City	Iowa
United States	South Denver Cardiology Associates PC	Littleton	Colorado
United States	North Dallas Research Associates	McKinney	Texas
United States	Aurora Saint Lukes Medical Center	Milwaukee	Wisconsin
United States	Weill Cornell Medicine	New York	New York
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Allegheny	Pittsburgh	Pennsylvania
United States	Vascular Medicine Institute University Of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Sharp Memorial Hospital	San Diego	California
United States	MultiCare Health System	Tacoma	Washington
United States	Baylor Scott & White Research Institute	Temple	Texas
United States	Harbor Ucla Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Bulgaria,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline to Week 24 in the Clinical Summary Score Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) Score	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
Secondary	Change From Baseline to Week 24 in Accelerometer-assessed Proportion of Time Spent in Light to Vigourous Physical Activity	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
Secondary	Number of Participants With Worsening of Heart Failure (WHF) Events Over 52 Weeks	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