MedPath

Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF

Phase 2
Completed
Conditions
Chronic Heart Failure With Preserved Ejection Fraction
Interventions
Registration Number
NCT03547583
Lead Sponsor
Bayer
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
789
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

Read More
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

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vericiguat up to 10 mgVericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tabletsSubjects 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.
Vericiguat up to 15 mgVericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tabletsSubjects 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.
PlaceboPlaceboSubject will receive placebo for 24 weeks, once daily, starting sham up-titration at weeks 2, 4, and 6.
Primary Outcome Measures
NameTimeMethod
Change in KCCQ Physical Limitation Score From Baseline to Week 24From baseline to Week 24

The City Cardiomyopathy Questionnaire (KCCQ) measures the impact of patients' heart failure, or its treatment, on 6 domains; Physical Limitation, Symptom (with subscores for frequency and burden), Quality of Life, Social Limitations, Symptom Stability and Self-Efficacy. Scores are calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status.

Secondary Outcome Measures
NameTimeMethod
Change in the Six-minute Walk Test (6MWT) From Baseline to Week 24From baseline to Week 24

6MWT was conducted to test the physical limitations of the patient by assessing the patient's exercise capacity. The distance walked by the patient in 6 minutes was measured.

Trial Locations

Locations (176)

Capitol Interventional Cardiology

🇺🇸

Carmichael, California, United States

Cardiovascular and Vein Center of Florida

🇺🇸

Bradenton, Florida, United States

Fox Valley Clinical Research Center, LLC

🇺🇸

Aurora, Illinois, United States

Corporation Lane Research Center

🇺🇸

Virginia Beach, Virginia, United States

PACE Cardiology Clinic

🇨🇦

Newmarket, Ontario, Canada

Tiervlei Trial Centre

🇿🇦

Cape Town, Western Cape, South Africa

Nash Ranjith Research Centre

🇿🇦

Merebank, Kwazulu-Natal, South Africa

Inst. de Cardiología de Corrientes Juana Francisca Cabral

🇦🇷

Corrientes, Argentina

Universitätsklinikum St. Pölten

🇦🇹

St. Pölten, Niederösterreich, Austria

MHAT Dr. Bratan Shukerov AD

🇧🇬

Smolyan, Bulgaria

Cardiology Associates Research Company

🇺🇸

Daytona Beach, Florida, United States

Riser Medical Associates

🇺🇸

Picayune, Mississippi, United States

Centro de Especialidades Médicas

🇦🇷

Villa Luro, Ciudad Auton. De Buenos Aires, Argentina

Medizinische Universität Graz

🇦🇹

Graz, Steiermark, Austria

Universitätsklinikum AKH Wien

🇦🇹

Wien, Austria

Cardiology Partners

🇺🇸

Wellington, Florida, United States

Heart Clinic of Hammond

🇺🇸

Hammond, Louisiana, United States

Sanatorio Parque S.A.

🇦🇷

Rosario, Santa Fe, Argentina

Klinik Floridsdorf - Krankenhaus Nord

🇦🇹

Wien, Austria

V MHAT

🇧🇬

Sofia, Bulgaria

Centre De Recherche Du (CRCHUM) - Hotel-Diu

🇨🇦

Montreal, Quebec, Canada

Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA

🇬🇷

Nea Ionia / Athens, Greece

Rambam Health Corporation

🇮🇱

Haifa, Israel

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

🇮🇱

Zefat, Israel

ASST Spedali Civili di Brescia

🇮🇹

Brescia, Lombardia, Italy

National Hospital Organization Kobe Medical Center

🇯🇵

Kobe, Hyogo, Japan

Iwate Prefectural Central Hospital

🇯🇵

Morioka, Iwate, Japan

Takatsuki Red Cross Hospital

🇯🇵

Takatsuki, Osaka, Japan

Zentrum für Klinische Studien Südbrandenburg GmbH

🇩🇪

Elsterwerda, Brandenburg, Germany

Minamino Cardiovascular Hospital

🇯🇵

Hachioji, Tokyo, Japan

Toho University Omori Medical Center

🇯🇵

Ota-ku, Tokyo, Japan

Twoja Przychodnia - Szczecinskie Centrum Medyczne

🇵🇱

Szczecin, Poland

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

Multiprofile Hospital for Active Treatment Medline Clinic

🇧🇬

Plovdiv, Bulgaria

St. Vincenz und Elisabeth Hospital, Kathol. Klinikum Mainz

🇩🇪

Mainz, Rheinland-Pfalz, Germany

Pharma4Trial Kft.

🇭🇺

Gyongyos, Hungary

Kaplan Medical Center

🇮🇱

Rehovot, Israel

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

🇮🇹

Bologna, Emilia-Romagna, Italy

KAT General Hospital of Athens

🇬🇷

Kifisia / Athens, Attica, Greece

Ordensklinikum Linz GmbH Elisabethinen

🇦🇹

Linz, Oberösterreich, Austria

Specialized Hospital for Actrive Treatm of Card - Pleven

🇧🇬

Pleven, Bulgaria

University General Hospital of Larissa

🇬🇷

Larissa, Greece

"AHEPA" University General Hospital of Thessaloniki

🇬🇷

Thessaloniki, Greece

Hippokration General Hospital of Thessaloniki

🇬🇷

Thessaloniki, Greece

Hadassah Hebrew University Hospital Ein Kerem

🇮🇱

Jerusalem, Israel

The Baruch Padeh Medical Center, Poria

🇮🇱

Tiberias, Israel

Shamir Medical Center (Assaf Harofeh)

🇮🇱

Zrifin, Israel

Steel Memorial Yawata Hospital

🇯🇵

Kitakyushu, Fukuoka, Japan

Hospital Garcia de Orta

🇵🇹

Almada, Portugal

St. Michael's Hospital Health Centre

🇨🇦

Toronto, Ontario, Canada

Stern Cardiovascular Center

🇺🇸

Germantown, Tennessee, United States

A.O.U. di Ferrara

🇮🇹

Ferrara, Emilia-Romagna, Italy

Hospital Clínico Universitario de Santiago de Compostela

🇪🇸

Santiago de Compostela, A Coruña, Spain

Multiprofile Hospital for Active Treatment Pazardzhik

🇧🇬

Pazardzhik, Bulgaria

Second Medical Center Sofia EOOD

🇧🇬

Sofia, Bulgaria

G. GENNIMATAS General State Hospital of Athens

🇬🇷

Athens, Greece

Oakville Cardiologists, Inc.

🇨🇦

Oakville, Ontario, Canada

Chaim Sheba Medical Center

🇮🇱

Ramat Gan, Israel

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

🇮🇹

Milano, Lombardia, Italy

ASST Grande Ospedale Metropolitano Niguarda

🇮🇹

Milano, Lombardia, Italy

Hirakata kohsai Hospital

🇯🇵

Hirakata, Osaka, Japan

Fukui Prefectural Hospital

🇯🇵

Fukui, Japan

Osaka General Medical Center

🇯🇵

Osaka, Japan

Toyama Prefectural Central Hospital

🇯🇵

Toyama, Japan

Hospital Raja Perempuan Zainab II

🇲🇾

Kelantan, Malaysia

10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ

🇵🇱

Bydgoszcz, Poland

CHLO - Hospital Sao Francisco Xavier

🇵🇹

Lisboa, Portugal

Higashi Takarazuka Satoh Hospital

🇯🇵

Takarazuka, Hyogo, Japan

Cardiovascular CRO Ltd.

🇨🇦

Sudbury, Ontario, Canada

Hospital General de Medellin

🇨🇴

Medellin, Antioquia, Colombia

Caja de Compensación Familiar CAFAM

🇨🇴

Bogotá, Distrito Capital De Bogotá, Colombia

Mediservis del Tolima IPS S.A.S

🇨🇴

Ibague, Tolima, Colombia

Klinikum der Universität Würzburg

🇩🇪

Würzburg, Bayern, Germany

Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)

🇩🇪

Bad Oeynhausen, Nordrhein-Westfalen, Germany

Klinische Forschung Dresden GmbH

🇩🇪

Dresden, Sachsen, Germany

Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.

🇭🇺

Nyiregyhaza, Hungary

ASST Papa Giovanni XXIII

🇮🇹

Bergamo, Lombardia, Italy

IRCCS Fondazione Policlinico San Matteo

🇮🇹

Pavia, Lombardia, Italy

A.O.U. di Sassari

🇮🇹

Sassari, Sardegna, Italy

CardioVasc HR, Inc.

🇨🇦

Saint-Jean-sur-Richelieu, Quebec, Canada

IPS Centro Cientifico Asistencial S.A.S

🇨🇴

Barranquilla, Atlántico, Colombia

Asl Roma 6

🇮🇹

Roma, Lazio, Italy

National Hospital Organization Kanazawa Medical Center

🇯🇵

Kanazawa, Ishikawa, Japan

Uji-Tokushukai Medical Center

🇯🇵

Uji, Kyoto, Japan

Okayama Rosai Hospital

🇯🇵

Okayama, Japan

Sarawak Heart Centre

🇲🇾

Sarawak, Malaysia

CLINICAL MEDICAL RESEARCH Sp. z o. o.

🇵🇱

Katowice, Poland

Hospital de Cascais

🇵🇹

Alcabideche, Lisboa, Portugal

CHTS - Hospital Padre Americo

🇵🇹

Guilhufe, Porto, Portugal

CHUP - Hospital Santo Antonio

🇵🇹

Porto, Portugal

Samara Regional Clinical Cardiology Dispensary n.a. Polyakov

🇷🇺

Samara, Russian Federation

Hospital Sant Joan Despi Moises Broggi

🇪🇸

Sant Joan Despi, Barcelona, Spain

National Hospital Organization Hamada Medical Center

🇯🇵

Hamada, Shimane, Japan

SPZOZ Centralny Szpital Kliniczny UM w Lodzi

🇵🇱

Lodz, Poland

IV Wojskowy Szpital Kliniczny z Poliklinika, SPZOZ

🇵🇱

Wroclaw, Poland

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

🇵🇱

Wroclaw, Poland

Singapore General Hospital

🇸🇬

Singapore, Singapore

National Heart Centre Singapore

🇸🇬

Singapore, Singapore

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

🇷🇺

Moscow, Russian Federation

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

Sci-Res. Institute of Complex Cardiovascular Disorders

🇷🇺

Kemerovo, Russian Federation

City hospital #15

🇷🇺

St. Petersburg, Russian Federation

Vergelegen Medi-Clinic

🇿🇦

Somerset West, Western Cape, South Africa

Far Eastern Memorial Hospital

🇨🇳

New Taipei City, Taiwan

CHS - Hospital Sao Bernardo

🇵🇹

Setubal, Setúbal, Portugal

Cheng Hsin General Hospital

🇨🇳

Taipei, Taiwan

Hospital da Luz - Lisboa

🇵🇹

Lisboa, Portugal

Ciutat Sanitària i Universitària de Bellvitge

🇪🇸

L'Hospitalet de Llobregat, Barcelona, Spain

St. Louis Heart & Vascular, PC

🇺🇸

Saint Louis, Missouri, United States

Interventional Cardiology Medical Group

🇺🇸

West Hills, California, United States

Anne Arundel Health System

🇺🇸

Annapolis, Maryland, United States

Centro de Investigaciones Clínicas

🇦🇷

Buenos Aires, Ciudad Auton. De Buenos Aires, Argentina

East Coast Institute for Research, LLC

🇺🇸

Saint Augustine, Florida, United States

Cardiology Associates Of South Florida PA

🇺🇸

Boynton Beach, Florida, United States

Research Integrity, LLC

🇺🇸

Owensboro, Kentucky, United States

Glacier View Research Institute

🇺🇸

Kalispell, Montana, United States

Cardiology Associates of Fairfield County, PC

🇺🇸

Trumbull, Connecticut, United States

LifeSpring Research Foundation, LLC

🇺🇸

Miami, Florida, United States

Southwest Florida Research

🇺🇸

Naples, Florida, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Carolina Heart Specialists

🇺🇸

Lancaster, South Carolina, United States

Centro de Investigaciones Clinicas del Litoral

🇦🇷

Santa Fe, Argentina

Bryan Heart

🇺🇸

Lincoln, Nebraska, United States

Clinical Advancement Center, PLLC

🇺🇸

San Antonio, Texas, United States

Clínica DIM

🇦🇷

Ramos Mejía, Buenos Aires, Argentina

UZ Antwerpen

🇧🇪

Edegem, Belgium

Instituto de Investigaciones Clínicas San Nicolás

🇦🇷

San Nicolás, Buenos Aires, Argentina

Centro de Medicina Integral e Investigacion Clínica

🇦🇷

Caba, Ciudad Auton. De Buenos Aires, Argentina

Zentrum f. klinische Studien Dr. Hanusch GmbH

🇦🇹

Wien, Austria

AZ St-Jan Brugge Oostende AV

🇧🇪

Brugge, Belgium

Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik

🇧🇬

Pernik, Bulgaria

Algemeen Stedelijk Ziekenhuis Campus Aalst

🇧🇪

Aalst, Belgium

NMTH Tzar Boris III

🇧🇬

Sofia, Bulgaria

Kliniken Maria Hilf GmbH

🇩🇪

Mönchengladbach, Nordrhein-Westfalen, Germany

SMH Cardiology Clinical Trials Inc

🇨🇦

Surrey, British Columbia, Canada

AZ Delta

🇧🇪

Roeselare, Belgium

Clinique Sante Cardio MC

🇨🇦

Montreal, Quebec, Canada

HaEmek Medical Center

🇮🇱

Afula, Israel

Budai Irgalmasrendi Korhaz

🇭🇺

Budapest, Hungary

Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz

🇭🇺

Budapest, Hungary

Fundación Cardiovascular de Colombia

🇨🇴

Floridablanca, Colombia

Kanizsai Dorottya Hospital

🇭🇺

Nagykanizsa, Hungary

Hillel Yaffe Medical Center

🇮🇱

Hadera, Israel

Seikeikai New Tokyo Heart Clinic

🇯🇵

Matsudo, Chiba, Japan

Osaka Medical College Hospital

🇯🇵

Takatsuki, Osaka, Japan

Kishiwada Tokushukai Hospital

🇯🇵

Kishiwada, Osaka, Japan

National Hospital Organization Iwakuni Clinical Center

🇯🇵

Iwakuni, Yamaguchi, Japan

Szpital Kliniczny Przemienienia Panskiego

🇵🇱

Poznan, Poland

Uniwersyteckie Centrum Kliniczne Warszawskiego UM

🇵🇱

Warszawa, Poland

Tokyo Women's Medical University Hospital

🇯🇵

Shinjuku-ku, Tokyo, Japan

Hospital del Mar

🇪🇸

Barcelona, Spain

Institute Jantung Negara

🇲🇾

Kuala Lumpur, Malaysia

Uniwersytecki Szpital Kliniczny w Bialymstoku

🇵🇱

Bialystok, Poland

Research center of therapy and prophylactic medicine

🇷🇺

Moscow, Russian Federation

TREAD Research cc

🇿🇦

Cape Town, Western Cape, South Africa

Clinical Trial Systems

🇿🇦

Pretoria, Gauteng, South Africa

City Pokrovskaya Hospital

🇷🇺

St. Petersburg, Russian Federation

Durban Medical Centre

🇿🇦

Durban, Kwazulu-Natal, South Africa

Hospital Universitario Clinica Puerta de Hierro

🇪🇸

Majadahonda, Madrid, Spain

Hospital Sanitas La Zarzuela

🇪🇸

Aravaca, Madrid, Spain

Hospital Álvaro Cunqueiro

🇪🇸

Babio - Beade, Pontevedra, Spain

Complejo Hospitalario Ntra. Sra. de Valme

🇪🇸

Sevilla, Spain

Hospital Virgen de la Victoria

🇪🇸

Málaga, Spain

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

WestSide Medical

🇺🇸

Beverly Hills, California, United States

Penrose-St. Francis Health Services

🇺🇸

Colorado Springs, Colorado, United States

Wake Forest Baptist Health

🇺🇸

Winston-Salem, North Carolina, United States

Capital Area Research, LLC

🇺🇸

Camp Hill, Pennsylvania, United States

Advocate Condell Medical Center

🇺🇸

Libertyville, Illinois, United States

Reid Health

🇺🇸

Richmond, Indiana, United States

Krankenhaus St. Josef Braunau

🇦🇹

Braunau, Oberösterreich, Austria

H. Hartziekenhuis Mol

🇧🇪

MOL, Belgium

London Health Sciences Centre

🇨🇦

London, Ontario, Canada

MHAT Sveta Marina EAD

🇧🇬

Varna, Bulgaria

Cardiologicum Hamburg - Praxen Wandsbek

🇩🇪

Hamburg, Germany

Matsuda Cardiovascular clinic

🇯🇵

Sapporo, Hokkaido, Japan

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