Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF

Chronic Heart Failure With Preserved Ejection Fraction Clinical Trial

— VITALITY-HFpEF  

Official title:

A Randomized Parallel-group, Placebo-controlled, Double-blind, Multi-center Trial to Evaluate the Efficacy and Safety of the Oral sGC stImulator Vericiguat to Improve Physical Functioning in Activities of Daily Living in Patients With Heart Failure and Preserved Ejection Fraction (VITALITY-HFpEF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03547583
• Other study ID #: 19334
• Secondary ID: 2018-000298-65
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2018
• Est. completion date: November 4, 2019

Study information

• Verified date: November 2020
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 789
• Est. completion date: November 4, 2019
• Est. primary completion date: October 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Heart Failure With Preserved Ejection Fraction
• Heart Failure

Intervention

Drug:
• 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.
• Placebo
Placebo and sham up-titration at weeks 2, 4, and 6

Locations

Country	Name	City	State
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	Inst. de Cardiología de Corrientes Juana Francisca Cabral	Corrientes
Argentina	Clínica DIM	Ramos Mejía	Buenos Aires
Argentina	Sanatorio Parque S.A.	Rosario	Santa Fe
Argentina	Instituto de Investigaciones Clínicas San Nicolás	San Nicolás	Buenos Aires
Argentina	Centro de Investigaciones Clinicas del Litoral	Santa Fe
Argentina	Centro de Especialidades Médicas	Villa Luro	Ciudad Auton. De Buenos Aires
Austria	Krankenhaus St. Josef Braunau	Braunau	Oberösterreich
Austria	Medizinische Universität Graz	Graz	Steiermark
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz	Oberösterreich
Austria	Universitätsklinikum St. Pölten	St. Pölten	Niederösterreich
Austria	Klinik Floridsdorf - Krankenhaus Nord	Wien
Austria	Universitätsklinikum AKH Wien	Wien
Austria	Zentrum f. klinische Studien Dr. Hanusch GmbH	Wien
Belgium	Algemeen Stedelijk Ziekenhuis Campus Aalst	Aalst
Belgium	AZ St-Jan Brugge Oostende AV	Brugge
Belgium	UZ Antwerpen	Edegem
Belgium	H. Hartziekenhuis Mol	MOL
Belgium	AZ Delta	Roeselare
Bulgaria	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	NMTH Tzar Boris III	Sofia
Bulgaria	Second Medical Center Sofia EOOD	Sofia
Bulgaria	V MHAT	Sofia
Bulgaria	MHAT Sveta Marina EAD	Varna
Canada	University of Alberta	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre De Recherche Du (CRCHUM) - Hotel-Diu	Montreal	Quebec
Canada	Clinique Sante Cardio MC	Montreal	Quebec
Canada	PACE Cardiology Clinic	Newmarket	Ontario
Canada	Oakville Cardiologists, Inc.	Oakville	Ontario
Canada	CardioVasc HR, Inc.	Saint-Jean-sur-Richelieu	Quebec
Canada	Cardiovascular CRO Ltd.	Sudbury	Ontario
Canada	SMH Cardiology Clinical Trials Inc	Surrey	British Columbia
Canada	St. Michael's Hospital Health Centre	Toronto	Ontario
Colombia	IPS Centro Cientifico Asistencial S.A.S	Barranquilla	Atlántico
Colombia	Caja de Compensación Familiar CAFAM	Bogotá	Distrito Capital De Bogotá
Colombia	Fundación Cardiovascular de Colombia	Floridablanca
Colombia	Mediservis del Tolima IPS S.A.S	Ibague	Tolima
Colombia	Hospital General de Medellin	Medellin	Antioquia
Germany	Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)	Bad Oeynhausen	Nordrhein-Westfalen
Germany	Klinische Forschung Dresden GmbH	Dresden	Sachsen
Germany	Zentrum für Klinische Studien Südbrandenburg GmbH	Elsterwerda	Brandenburg
Germany	Cardiologicum Hamburg - Praxen Wandsbek	Hamburg
Germany	St. Vincenz und Elisabeth Hospital, Kathol. Klinikum Mainz	Mainz	Rheinland-Pfalz
Germany	Kliniken Maria Hilf GmbH	Mönchengladbach	Nordrhein-Westfalen
Germany	Klinikum der Universität Würzburg	Würzburg	Bayern
Greece	G. GENNIMATAS General State Hospital of Athens	Athens
Greece	KAT General Hospital of Athens	Kifisia / Athens	Attica
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
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz	Budapest
Hungary	Pharma4Trial Kft.	Gyongyos
Hungary	Kanizsai Dorottya Hospital	Nagykanizsa
Hungary	Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.	Nyiregyhaza
Israel	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	The Baruch Padeh Medical Center, Poria	Tiberias
Israel	Health Corporation of the Ziv Medical Center (R.A.)	Zefat
Israel	Shamir Medical Center (Assaf Harofeh)	Zrifin
Italy	ASST Papa Giovanni XXIII	Bergamo	Lombardia
Italy	A.O.U. di Bologna Policlinico S.Orsola Malpighi	Bologna	Emilia-Romagna
Italy	ASST Spedali Civili di Brescia	Brescia	Lombardia
Italy	A.O.U. di Ferrara	Ferrara	Emilia-Romagna
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano	Lombardia
Italy	IRCCS Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.	Milano	Lombardia
Italy	IRCCS Fondazione Policlinico San Matteo	Pavia	Lombardia
Italy	Asl Roma 6	Roma	Lazio
Italy	A.O.U. di Sassari	Sassari	Sardegna
Japan	Fukui Prefectural Hospital	Fukui
Japan	Minamino Cardiovascular Hospital	Hachioji	Tokyo
Japan	National Hospital Organization Hamada Medical Center	Hamada	Shimane
Japan	Hirakata kohsai Hospital	Hirakata	Osaka
Japan	National Hospital Organization Iwakuni Clinical Center	Iwakuni	Yamaguchi
Japan	National Hospital Organization Kanazawa Medical Center	Kanazawa	Ishikawa
Japan	Kishiwada Tokushukai Hospital	Kishiwada	Osaka
Japan	Steel Memorial Yawata Hospital	Kitakyushu	Fukuoka
Japan	National Hospital Organization Kobe Medical Center	Kobe	Hyogo
Japan	Seikeikai New Tokyo Heart Clinic	Matsudo	Chiba
Japan	Iwate Prefectural Central Hospital	Morioka	Iwate
Japan	Okayama Rosai Hospital	Okayama
Japan	Osaka General Medical Center	Osaka
Japan	Toho University Omori Medical Center	Ota-ku	Tokyo
Japan	Matsuda Cardiovascular clinic	Sapporo	Hokkaido
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo
Japan	Higashi Takarazuka Satoh Hospital	Takarazuka	Hyogo
Japan	Osaka Medical College Hospital	Takatsuki	Osaka
Japan	Takatsuki Red Cross Hospital	Takatsuki	Osaka
Japan	Toyama Prefectural Central Hospital	Toyama
Japan	Uji-Tokushukai Medical Center	Uji	Kyoto
Malaysia	Hospital Raja Perempuan Zainab II	Kelantan
Malaysia	Institute Jantung Negara	Kuala Lumpur
Malaysia	Sarawak Heart Centre	Sarawak
Poland	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	Warszawa
Poland	Dolnoslaski Szp. Spec. im T.M. Centrum Medycyny Ratunkowej	Wroclaw
Poland	IV Wojskowy Szpital Kliniczny z Poliklinika, SPZOZ	Wroclaw
Portugal	Hospital de Cascais	Alcabideche	Lisboa
Portugal	Hospital Garcia de Orta	Almada
Portugal	CHTS - Hospital Padre Americo	Guilhufe	Porto
Portugal	CHLO - Hospital Sao Francisco Xavier	Lisboa
Portugal	Hospital da Luz - Lisboa	Lisboa
Portugal	CHUP - Hospital Santo Antonio	Porto
Portugal	CHS - Hospital Sao Bernardo	Setubal	Setúbal
Russian Federation	Sci-Res. Institute of Complex Cardiovascular Disorders	Kemerovo
Russian Federation	Moscow State University n.a. M.V. Lomonosov	Moscow
Russian Federation	Research center of therapy and prophylactic medicine	Moscow
Russian Federation	Samara Regional Clinical Cardiology Dispensary n.a. Polyakov	Samara
Russian Federation	City hospital #15	St. Petersburg
Russian Federation	City Pokrovskaya Hospital	St. Petersburg
Singapore	National Heart Centre Singapore	Singapore
Singapore	Singapore General Hospital	Singapore
South Africa	Tiervlei Trial Centre	Cape Town	Western Cape
South Africa	TREAD Research cc	Cape Town	Western Cape
South Africa	Durban Medical Centre	Durban	Kwazulu-Natal
South Africa	Nash Ranjith Research Centre	Merebank	Kwazulu-Natal
South Africa	Clinical Trial Systems	Pretoria	Gauteng
South Africa	Vergelegen Medi-Clinic	Somerset West	Western Cape
Spain	Hospital Sanitas La Zarzuela	Aravaca	Madrid
Spain	Hospital Álvaro Cunqueiro	Babio - Beade	Pontevedra
Spain	Hospital del Mar	Barcelona
Spain	Ciutat Sanitària i Universitària de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Clinica Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Virgen de la Victoria	Málaga
Spain	Hospital Sant Joan Despi Moises Broggi	Sant Joan Despi	Barcelona
Spain	Hospital Clínico Universitario de Santiago de Compostela	Santiago de Compostela	A Coruña
Spain	Complejo Hospitalario Ntra. Sra. de Valme	Sevilla
Taiwan	Far Eastern Memorial Hospital	New Taipei City
Taiwan	Cheng Hsin General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Anne Arundel Health System	Annapolis	Maryland
United States	Fox Valley Clinical Research Center, LLC	Aurora	Illinois
United States	WestSide Medical	Beverly Hills	California
United States	Cardiology Associates Of South Florida PA	Boynton Beach	Florida
United States	Cardiovascular and Vein Center of Florida	Bradenton	Florida
United States	Capital Area Research, LLC	Camp Hill	Pennsylvania
United States	Capitol Interventional Cardiology	Carmichael	California
United States	Penrose-St. Francis Health Services	Colorado Springs	Colorado
United States	Cardiology Associates Research Company	Daytona Beach	Florida
United States	Henry Ford Health System	Detroit	Michigan
United States	Stern Cardiovascular Center	Germantown	Tennessee
United States	Heart Clinic of Hammond	Hammond	Louisiana
United States	Glacier View Research Institute	Kalispell	Montana
United States	Carolina Heart Specialists	Lancaster	South Carolina
United States	Advocate Condell Medical Center	Libertyville	Illinois
United States	Bryan Heart	Lincoln	Nebraska
United States	LifeSpring Research Foundation, LLC	Miami	Florida
United States	Southwest Florida Research	Naples	Florida
United States	Research Integrity, LLC	Owensboro	Kentucky
United States	Riser Medical Associates	Picayune	Mississippi
United States	Reid Health	Richmond	Indiana
United States	East Coast Institute for Research, LLC	Saint Augustine	Florida
United States	St. Louis Heart & Vascular, PC	Saint Louis	Missouri
United States	Clinical Advancement Center, PLLC	San Antonio	Texas
United States	Cardiology Associates of Fairfield County, PC	Trumbull	Connecticut
United States	Corporation Lane Research Center	Virginia Beach	Virginia
United States	Cardiology Partners	Wellington	Florida
United States	Interventional Cardiology Medical Group	West Hills	California
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Bayer	Canadian VIGOUR Centre, Duke Clinical Research Institute, Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

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

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment Emergent Adverse Events	An AE is any untoward medical occurrence (i.e. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation patient after providing written informed consent for participation in the study. Adverse events are considered to be treatment-emergent if they have started or worsened after first application of study medication up to 5 calendar days after end of treatment with study medication.	From first application of study drug up to 5 calendar days after end of treatment with study drug
Primary	Change in KCCQ Physical Limitation Score From 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.	From baseline to Week 24
Secondary	Change in the Six-minute Walk Test (6MWT) From 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.	From baseline to Week 24

External Links

•   Click here to find information about studies related to Bayer Healthcare products conducted in Europe
•   Click here to find results for studies related to Bayer products