Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF

NCT ID: NCT03547583

Last Updated: 2021-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 789 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-15
• Study Completion Date: 2019-11-04

Brief Summary

The primary hypothesis in this trial is that the treatment with vericiguat 10 mg or 15 mg in patients with HFpEF improves the KCCQ PLS (Kansas City Cardiomyopathy Questionnaire Physical limitation score) compared to placebo after 24 weeks of treatment.

Conditions

Chronic Heart Failure With Preserved Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vericiguat up to 10 mg

Subjects will receive vericiguat (BAY1021189) for 24 weeks, starting at 2.5 mg once daily at randomization and up-titrated to 5 mg at week 2, to 10 mg at week 4, with sham titration at week 6.

Group Type: EXPERIMENTAL

Vericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tablets

Intervention Type: DRUG

Oral use. Vericiguat, which will be started at 2.5 mg at randomization and up-titrated to 5 mg at week 2, and to 10 mg at week 4, with sham titration or up-titration to 15 mg at week 6.

Vericiguat up to 15 mg

Subjects will receive vericiguat (BAY1021189) for 24 weeks, starting at 2.5 mg once daily at randomization and up-titrated to 5 mg at week 2, to 10 mg at week 4, and to 15 mg at week 6.

Group Type: EXPERIMENTAL

Vericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tablets

Intervention Type: DRUG

Oral use. Vericiguat, which will be started at 2.5 mg at randomization and up-titrated to 5 mg at week 2, and to 10 mg at week 4, with sham titration or up-titration to 15 mg at week 6.

Placebo

Subject will receive placebo for 24 weeks, once daily, starting sham up-titration at weeks 2, 4, and 6.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo and sham up-titration at weeks 2, 4, and 6

Interventions

Vericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tablets

Oral use. Vericiguat, which will be started at 2.5 mg at randomization and up-titrated to 5 mg at week 2, and to 10 mg at week 4, with sham titration or up-titration to 15 mg at week 6.

Intervention Type: DRUG

Placebo

Placebo and sham up-titration at weeks 2, 4, and 6

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Previous diagnosis of chronic heart failure (HF)
• HF decompensation within 6 months prior to randomization, defined as hospitalization for HF or intravenous (IV) diuretic treatment for HF without hospitalization.
• N-terminal pro brain natriuretic peptide (NT-proBNP) ≥300 or brain natriuretic peptide (BNP) ≥100 pg/mL in sinus rhythm, or NT-proBNP

≥600 or BNP ≥200 pg/mL in atrial fibrillation within 30 days prior to randomization

• Diagnostic criteria of HFpEF by echocardiography assessed within 12 months prior to randomization (most recent measurement must be used to determine eligibility with no interim event signaling potential deterioration in ejection fraction)

• Left ventricular ejection fraction (LVEF) ≥45% and
• Structural changes indicated by at least one of the following parameters:

• Left ventricle (LV) hypertrophy (any of the following: intraventricular septal or posterior wall thickness ≥1.1 cm, and/or LV mass index ≥115 g/m*2 in male and ≥95 g/m*2 in female), or
• Left atrium (LA) enlargement (any of the following: left atrial volume (LAV) index ≥29 ml/m*2, or LAV >58 mL in male and >52 mL in female patients, or LA area >20 cm*2, or LA diameter >40 mm in male and >38 mm in female patients)
• NYHA class II or III at randomization

Exclusion Criteria

• Clinical instability at randomization, defined by

• Any IV treatment within 24h prior to randomization, and/or
• SBP ≥160 mmHg
• SBP <110 mmHg and/or DBP <40 mmHg and/or symptomatic hypotension
• Resting heart rate (HR) <50 or ≥100 beats per minute (bpm)
• Use of IV inotropes at any time between qualifying HF event and randomization
• Previous diagnosis of reduced ejection fraction (EF) (EF <40%)
• Hypertrophic obstructive cardiomyopathy, acute myocarditis, amyloidosis, sarcoidosis, or pericardial disease
• Primary valvular heart disease requiring surgery or intervention, or within 3 months after valvular surgery or intervention, or active endocarditis
• Acute coronary syndrome, including unstable angina, Non ST-elevation myocardial infarction or ST-elevation myocardial infarction, or Coronary artery bypass grafting (CABG) within 60 days prior to randomization, or indication for Percutaneous coronary intervention or CABG at the time of randomization
• Symptomatic carotid stenosis, or transient ischemic attack or stroke within 60 days prior to randomization
• Complex congenital heart disease
• Non-cardiac comorbidity (any of the following)

• Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m*2 calculated by Modification of Diet in Renal Disease formula
• Hepatic insufficiency classified as Child-Pugh B or C
• Morbid obesity with a body mass index >45 kg/m*2
• Malignancy or other non-cardiac condition limiting life expectancy to <1 year, per physician judgment
• Requires continuous home oxygen for severe pulmonary disease or has interstitial lung disease
• Patients with allergies, intolerance or hypersensitivity to investigational drug or any of the excipients
• Concurrent or anticipated use of nitrates or NO donors, phosphodiesterase type V (PDE5) inhibitors, or a Soluble guanylate cyclase (sGC) stimulator

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Canadian VIGOUR Centre

OTHER

Sponsor Role: collaborator

Duke Clinical Research Institute

OTHER

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

WestSide Medical

Beverly Hills, California, United States

Capitol Interventional Cardiology

Carmichael, California, United States

Interventional Cardiology Medical Group

West Hills, California, United States

Penrose-St. Francis Health Services

Colorado Springs, Colorado, United States

Cardiology Associates of Fairfield County, PC

Trumbull, Connecticut, United States

Cardiology Associates Of South Florida PA

Boynton Beach, Florida, United States

Cardiovascular and Vein Center of Florida

Bradenton, Florida, United States

Cardiology Associates Research Company

Daytona Beach, Florida, United States

LifeSpring Research Foundation, LLC

Miami, Florida, United States

Southwest Florida Research

Naples, Florida, United States

East Coast Institute for Research, LLC

Saint Augustine, Florida, United States

Cardiology Partners

Wellington, Florida, United States

Fox Valley Clinical Research Center, LLC

Aurora, Illinois, United States

Advocate Condell Medical Center

Libertyville, Illinois, United States

Reid Health

Richmond, Indiana, United States

Research Integrity, LLC

Owensboro, Kentucky, United States

Heart Clinic of Hammond

Hammond, Louisiana, United States

Anne Arundel Health System

Annapolis, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

Riser Medical Associates

Picayune, Mississippi, United States

St. Louis Heart & Vascular, PC

St Louis, Missouri, United States

Glacier View Research Institute

Kalispell, Montana, United States

Bryan Heart

Lincoln, Nebraska, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Capital Area Research, LLC

Camp Hill, Pennsylvania, United States

Carolina Heart Specialists

Lancaster, South Carolina, United States

Stern Cardiovascular Center

Germantown, Tennessee, United States

Clinical Advancement Center, PLLC

San Antonio, Texas, United States

Corporation Lane Research Center

Virginia Beach, Virginia, United States

Clínica DIM

Ramos Mejía, Buenos Aires, Argentina

Instituto de Investigaciones Clínicas San Nicolás

San Nicolás de los Arroyos, Buenos Aires, Argentina

Centro de Investigaciones Clínicas

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Centro de Medicina Integral e Investigacion Clínica

CABA, Ciudad Auton. de Buenos Aires, Argentina

Centro de Especialidades Médicas

Villa Luro, Ciudad Auton. de Buenos Aires, Argentina

Sanatorio Parque S.A.

Rosario, Santa Fe Province, Argentina

Inst. de Cardiología de Corrientes Juana Francisca Cabral

Corrientes, , Argentina

Centro de Investigaciones Clinicas del Litoral

Santa Fe, , Argentina

Universitätsklinikum St. Pölten

Sankt Pölten, Lower Austria, Austria

Medizinische Universität Graz

Graz, Styria, Austria

Krankenhaus St. Josef Braunau

Braunau am Inn, Upper Austria, Austria

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, Austria

Zentrum f. klinische Studien Dr. Hanusch GmbH

Vienna, , Austria

Universitätsklinikum AKH Wien

Vienna, , Austria

Klinik Floridsdorf - Krankenhaus Nord

Vienna, , Austria

Algemeen Stedelijk Ziekenhuis Campus Aalst

Aalst, , Belgium

AZ St-Jan Brugge Oostende AV

Bruges, , Belgium

UZ Antwerpen

Edegem, , Belgium

H. Hartziekenhuis Mol

Mol, , Belgium

AZ Delta

Roeselare, , Belgium

Multiprofile Hospital for Active Treatment Pazardzhik

Pazardzhik, , Bulgaria

Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik

Pernik, , Bulgaria

Specialized Hospital for Actrive Treatm of Card - Pleven

Pleven, , Bulgaria

Multiprofile Hospital for Active Treatment Medline Clinic

Plovdiv, , Bulgaria

MHAT Dr. Bratan Shukerov AD

Smolyan, , Bulgaria

Second Medical Center Sofia EOOD

Sofia, , Bulgaria

NMTH Tzar Boris III

Sofia, , Bulgaria

V MHAT

Sofia, , Bulgaria

MHAT Sveta Marina EAD

Varna, , Bulgaria

University of Alberta

Edmonton, Alberta, Canada

SMH Cardiology Clinical Trials Inc

Surrey, British Columbia, Canada

Cardiovascular CRO Ltd.

Greater Sudbury, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

PACE Cardiology Clinic

Newmarket, Ontario, Canada

Oakville Cardiologists, Inc.

Oakville, Ontario, Canada

St. Michael's Hospital Health Centre

Toronto, Ontario, Canada

Clinique Sante Cardio MC

Montreal, Quebec, Canada

Centre De Recherche Du (CRCHUM) - Hotel-Diu

Montreal, Quebec, Canada

CardioVasc HR, Inc.

Saint-Jean-sur-Richelieu, Quebec, Canada

Hospital General de Medellin

Medellín, Antioquia, Colombia

IPS Centro Cientifico Asistencial S.A.S

Barranquilla, Atlántico, Colombia

Caja de Compensación Familiar CAFAM

Bogotá, Bogota D.C., Colombia

Mediservis del Tolima IPS S.A.S

Ibagué, Tolima Department, Colombia

Fundación Cardiovascular de Colombia

Floridablanca, , Colombia

Klinikum der Universität Würzburg

Würzburg, Bavaria, Germany

Zentrum für Klinische Studien Südbrandenburg GmbH

Elsterwerda, Brandenburg, Germany

Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)

Bad Oeynhausen, North Rhine-Westphalia, Germany

Kliniken Maria Hilf GmbH

Mönchengladbach, North Rhine-Westphalia, Germany

St. Vincenz und Elisabeth Hospital, Kathol. Klinikum Mainz

Mainz, Rhineland-Palatinate, Germany

Klinische Forschung Dresden GmbH

Dresden, Saxony, Germany

Cardiologicum Hamburg - Praxen Wandsbek

Hamburg, , Germany

KAT General Hospital of Athens

Kifisia / Athens, Attica, Greece

G. GENNIMATAS General State Hospital of Athens

Athens, , Greece

University General Hospital of Larissa

Larissa, , Greece

Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA

Nea Ionia / Athens, , Greece

"AHEPA" University General Hospital of Thessaloniki

Thessaloniki, , Greece

Hippokration General Hospital of Thessaloniki

Thessaloniki, , Greece

Budai Irgalmasrendi Korhaz

Budapest, , Hungary

Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz

Budapest, , Hungary

Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz

Budapest, , Hungary

Pharma4Trial Kft.

Gyöngyös, , Hungary

Kanizsai Dorottya Hospital

Nagykanizsa, , Hungary

Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.

Nyíregyháza, , Hungary

HaEmek Medical Center

Afula, , Israel

Hillel Yaffe Medical Center

Hadera, , Israel

Rambam Health Corporation

Haifa, , Israel

Hadassah Hebrew University Hospital Ein Kerem

Jerusalem, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Kaplan Medical Center

Rehovot, , Israel

Health Corporation of the Ziv Medical Center (R.A.)

Safed, , Israel

The Baruch Padeh Medical Center, Poria

Tiberias, , Israel

Shamir Medical Center (Assaf Harofeh)

Zrifin, , Israel

A.O.U. di Bologna Policlinico S.Orsola Malpighi

Bologna, Emilia-Romagna, Italy

A.O.U. di Ferrara

Ferrara, Emilia-Romagna, Italy

Asl Roma 6

Rome, Lazio, Italy

ASST Papa Giovanni XXIII

Bergamo, Lombardy, Italy

ASST Spedali Civili di Brescia

Brescia, Lombardy, Italy

IRCCS Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.

Milan, Lombardy, Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, Italy

IRCCS Fondazione Policlinico San Matteo

Pavia, Lombardy, Italy

A.O.U. di Sassari

Sassari, Sardinia, Italy

Seikeikai New Tokyo Heart Clinic

Matsudo, Chiba, Japan

Steel Memorial Yawata Hospital

Kitakyushu, Fukuoka, Japan

Matsuda Cardiovascular clinic

Sapporo, Hokkaido, Japan

National Hospital Organization Kobe Medical Center

Kobe, Hyōgo, Japan

Higashi Takarazuka Satoh Hospital

Takarazuka, Hyōgo, Japan

National Hospital Organization Kanazawa Medical Center

Kanazawa, Ishikawa-ken, Japan

Iwate Prefectural Central Hospital

Morioka, Iwate, Japan

Uji-Tokushukai Medical Center

Uji, Kyoto, Japan

Hirakata kohsai Hospital

Hirakata, Osaka, Japan

Kishiwada Tokushukai Hospital

Kishiwada, Osaka, Japan

Takatsuki Red Cross Hospital

Takatsuki, Osaka, Japan

Osaka Medical College Hospital

Takatsuki, Osaka, Japan

National Hospital Organization Hamada Medical Center

Hamada, Shimane, Japan

Minamino Cardiovascular Hospital

Hachiōji, Tokyo, Japan

Toho University Omori Medical Center

Ōta-ku, Tokyo, Japan

Tokyo Women's Medical University Hospital

Shinjuku-ku, Tokyo, Japan

National Hospital Organization Iwakuni Clinical Center

Iwakuni, Yamaguchi, Japan

Fukui Prefectural Hospital

Fukui, , Japan

Okayama Rosai Hospital

Okayama, , Japan

Osaka General Medical Center

Osaka, , Japan

Toyama Prefectural Central Hospital

Toyama, , Japan

Hospital Raja Perempuan Zainab II

Kelantan, , Malaysia

Institute Jantung Negara

Kuala Lumpur, , Malaysia

Sarawak Heart Centre

Sarawak, , Malaysia

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, , Poland

10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ

Bydgoszcz, , Poland

CLINICAL MEDICAL RESEARCH Sp. z o. o.

Katowice, , Poland

SPZOZ Centralny Szpital Kliniczny UM w Lodzi

Lodz, , Poland

Szpital Kliniczny Przemienienia Panskiego

Poznan, , Poland

Twoja Przychodnia - Szczecinskie Centrum Medyczne

Szczecin, , Poland

Uniwersyteckie Centrum Kliniczne Warszawskiego UM

Warsaw, , Poland

IV Wojskowy Szpital Kliniczny z Poliklinika, SPZOZ

Wroclaw, , Poland

Dolnoslaski Szp. Spec. im T.M. Centrum Medycyny Ratunkowej

Wroclaw, , Poland

Hospital de Cascais

Alcabideche, Lisbon District, Portugal

CHTS - Hospital Padre Americo

Guilhufe, Porto District, Portugal

CHS - Hospital Sao Bernardo

Setúbal, Setúbal District, Portugal

Hospital Garcia de Orta

Almada, , Portugal

CHLO - Hospital Sao Francisco Xavier

Lisbon, , Portugal

Hospital da Luz - Lisboa

Lisbon, , Portugal

CHUP - Hospital Santo Antonio

Porto, , Portugal

Sci-Res. Institute of Complex Cardiovascular Disorders

Kemerovo, , Russia

Research center of therapy and prophylactic medicine

Moscow, , Russia

Moscow State University n.a. M.V. Lomonosov

Moscow, , Russia

City hospital #15

Saint Petersburg, , Russia

City Pokrovskaya Hospital

Saint Petersburg, , Russia

Samara Regional Clinical Cardiology Dispensary n.a. Polyakov

Samara, , Russia

Singapore General Hospital

Singapore, , Singapore

National Heart Centre Singapore

Singapore, , Singapore

Clinical Trial Systems

Pretoria, Gauteng, South Africa

Durban Medical Centre

Durban, KwaZulu-Natal, South Africa

Nash Ranjith Research Centre

Merebank, KwaZulu-Natal, South Africa

TREAD Research cc

Cape Town, Western Cape, South Africa

Tiervlei Trial Centre

Cape Town, Western Cape, South Africa

Vergelegen Medi-Clinic

Somerset West, Western Cape, South Africa

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, A Coruña, Spain

Ciutat Sanitària i Universitària de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Sant Joan Despi Moises Broggi

Sant Joan Despí, Barcelona, Spain

Hospital Sanitas La Zarzuela

Aravaca, Madrid, Spain

Hospital Universitario Clinica Puerta de Hierro

Majadahonda, Madrid, Spain

Hospital Álvaro Cunqueiro

Babio - Beade, Pontevedra, Spain

Hospital del Mar

Barcelona, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

Complejo Hospitalario Ntra. Sra. de Valme

Seville, , Spain

Far Eastern Memorial Hospital

New Taipei City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Cheng Hsin General Hospital

Taipei, , Taiwan

Countries

United States; Argentina; Austria; Belgium; Bulgaria; Canada; Colombia; Germany; Greece; Hungary; Israel; Italy; Japan; Malaysia; Poland; Portugal; Russia; Singapore; South Africa; Spain; Taiwan

References

Butler J, Lam CSP, Anstrom KJ, Ezekowitz J, Hernandez AF, O'Connor CM, Pieske B, Ponikowski P, Shah SJ, Solomon SD, Voors AA, Wu Y, Carvalho F, Bamber L, Blaustein RO, Roessig L, Armstrong PW. Rationale and Design of the VITALITY-HFpEF Trial. Circ Heart Fail. 2019 May;12(5):e005998. doi: 10.1161/CIRCHEARTFAILURE.119.005998.

Reference Type: BACKGROUND

PMID: 31096775 (View on PubMed)

deFilippi CR, Shah P, Shah SJ, Alemayehu W, Lam CSP, Butler J, Roessig L, O'Connor CM, Westerhout CM, Armstrong PW; VITALITY-HFpEF Study Group. Proteomics Identify Clinical Phenotypes and Predict Functional Outcomes in Heart Failure With Preserved Ejection Fraction: Insights From VITALITY-HFpEF. Circ Heart Fail. 2024 Sep;17(9):e011792. doi: 10.1161/CIRCHEARTFAILURE.124.011792. Epub 2024 Aug 29.

Reference Type: DERIVED

PMID: 39206547 (View on PubMed)

Kaul P, Rathwell S, Lam CSP, Westerhout CM, Spertus JA, Anstrom KJ, Blaustein RO, Ezekowitz JA, Pieske B, Roessig L, Butler J, Armstrong PW; VITALITY-HFpEF Study Group. Patient-Reported Frailty and Functional Status in Heart Failure With Preserved Ejection Fraction: Insights From VITALITY-HFpEF. JACC Heart Fail. 2023 Apr;11(4):392-403. doi: 10.1016/j.jchf.2022.11.015. Epub 2023 Feb 1.

Reference Type: DERIVED

PMID: 36881394 (View on PubMed)

Armstrong PW, Lam CSP, Anstrom KJ, Ezekowitz J, Hernandez AF, O'Connor CM, Pieske B, Ponikowski P, Shah SJ, Solomon SD, Voors AA, She L, Vlajnic V, Carvalho F, Bamber L, Blaustein RO, Roessig L, Butler J; VITALITY-HFpEF Study Group. Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial. JAMA. 2020 Oct 20;324(15):1512-1521. doi: 10.1001/jama.2020.15922.

Reference Type: DERIVED

PMID: 33079152 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

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http://www.clinicaltrialsregister.eu/

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Other Identifiers

2018-000298-65

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

19334

Identifier Type: -

Identifier Source: org_study_id