Clinical trial NCT03547583: Patient-reported Outcomes in Vericiguat-treated Patients With 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Heart Failure With Preserved Ejection Fraction
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
name: Canadian VIGOUR Centre
name: Duke Clinical Research Institute
First posted: 2018-06-06
Enrollment: 789
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in KCCQ Physical Limitation Score From Baseline to Week 24
timeFrame: From baseline to Week 24
Secondary outcomes:
measure: Change in the Six-minute Walk Test (6MWT) From Baseline to Week 24
timeFrame: From baseline to Week 24
Other outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From first application of study drug up to 5 calendar days after end of treatment with study drug
Locations:
city: Beverly Hills
country: United States
facility: WestSide Medical
state: California
city: Carmichael
country: United States
facility: Capitol Interventional Cardiology
state: California
city: West Hills
country: United States
facility: Interventional Cardiology Medical Group
state: California
city: Colorado Springs
country: United States
facility: Penrose-St. Francis Health Services
state: Colorado
city: Trumbull
country: United States
facility: Cardiology Associates of Fairfield County, PC
state: Connecticut
city: Boynton Beach
country: United States
facility: Cardiology Associates Of South Florida PA
state: Florida
city: Bradenton
country: United States
facility: Cardiovascular and Vein Center of Florida
state: Florida
city: Daytona Beach
country: United States
facility: Cardiology Associates Research Company
state: Florida
city: Miami
country: United States
facility: LifeSpring Research Foundation, LLC
state: Florida
city: Naples
country: United States
facility: Southwest Florida Research
state: Florida
city: Saint Augustine
country: United States
facility: East Coast Institute for Research, LLC
state: Florida
city: Wellington
country: United States
facility: Cardiology Partners
state: Florida
city: Aurora
country: United States
facility: Fox Valley Clinical Research Center, LLC
state: Illinois
city: Libertyville
country: United States
facility: Advocate Condell Medical Center
state: Illinois
city: Richmond
country: United States
facility: Reid Health
state: Indiana
city: Owensboro
country: United States
facility: Research Integrity, LLC
state: Kentucky
city: Hammond
country: United States
facility: Heart Clinic of Hammond
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Health System
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Picayune
country: United States
facility: Riser Medical Associates
state: Mississippi
city: Saint Louis
country: United States
facility: St. Louis Heart & Vascular, PC
state: Missouri
city: Kalispell
country: United States
facility: Glacier View Research Institute
state: Montana
city: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Camp Hill
country: United States
facility: Capital Area Research, LLC
state: Pennsylvania
city: Lancaster
country: United States
facility: Carolina Heart Specialists
state: South Carolina
city: Germantown
country: United States
facility: Stern Cardiovascular Center
state: Tennessee
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: Virginia Beach
country: United States
facility: Corporation Lane Research Center
state: Virginia
city: Ramos Mejía
country: Argentina
facility: Clínica DIM
state: Buenos Aires
city: San Nicolás
country: Argentina
facility: Instituto de Investigaciones Clínicas San Nicolás
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Centro de Investigaciones Clínicas
state: Ciudad Auton. De Buenos Aires
city: Caba
country: Argentina
facility: Centro de Medicina Integral e Investigacion Clínica
state: Ciudad Auton. De Buenos Aires
city: Villa Luro
country: Argentina
facility: Centro de Especialidades Médicas
state: Ciudad Auton. De Buenos Aires
city: Rosario
country: Argentina
facility: Sanatorio Parque S.A.
state: Santa Fe
city: Corrientes
country: Argentina
facility: Inst. de Cardiología de Corrientes Juana Francisca Cabral
city: Santa Fe
country: Argentina
facility: Centro de Investigaciones Clinicas del Litoral
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
state: Niederösterreich
city: Braunau
country: Austria
facility: Krankenhaus St. Josef Braunau
state: Oberösterreich
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
state: Oberösterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Wien
country: Austria
facility: Zentrum f. klinische Studien Dr. Hanusch GmbH
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Klinik Floridsdorf - Krankenhaus Nord
city: Aalst
country: Belgium
facility: Algemeen Stedelijk Ziekenhuis Campus Aalst
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge Oostende AV
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: MOL
country: Belgium
facility: H. Hartziekenhuis Mol
city: Roeselare
country: Belgium
facility: AZ Delta
city: Pazardzhik
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Pazardzhik
city: Pernik
country: Bulgaria
facility: Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik
city: Pleven
country: Bulgaria
facility: Specialized Hospital for Actrive Treatm of Card - Pleven
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Medline Clinic
city: Smolyan
country: Bulgaria
facility: MHAT Dr. Bratan Shukerov AD
city: Sofia
country: Bulgaria
facility: Second Medical Center Sofia EOOD
city: Sofia
country: Bulgaria
facility: NMTH Tzar Boris III
city: Sofia
country: Bulgaria
facility: V MHAT
city: Varna
country: Bulgaria
facility: MHAT Sveta Marina EAD
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Surrey
country: Canada
facility: SMH Cardiology Clinical Trials Inc
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: PACE Cardiology Clinic
state: Ontario
city: Oakville
country: Canada
facility: Oakville Cardiologists, Inc.
state: Ontario
city: Sudbury
country: Canada
facility: Cardiovascular CRO Ltd.
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital Health Centre
state: Ontario
city: Montreal
country: Canada
facility: Clinique Sante Cardio MC
state: Quebec
city: Montreal
country: Canada
facility: Centre De Recherche Du (CRCHUM) - Hotel-Diu
state: Quebec
city: Saint-Jean-sur-Richelieu
country: Canada
facility: CardioVasc HR, Inc.
state: Quebec
city: Medellin
country: Colombia
facility: Hospital General de Medellin
state: Antioquia
city: Barranquilla
country: Colombia
facility: IPS Centro Cientifico Asistencial S.A.S
state: Atlántico
city: Bogotá
country: Colombia
facility: Caja de Compensación Familiar CAFAM
state: Distrito Capital De Bogotá
city: Ibague
country: Colombia
facility: Mediservis del Tolima IPS S.A.S
state: Tolima
city: Floridablanca
country: Colombia
facility: Fundación Cardiovascular de Colombia
city: Würzburg
country: Germany
facility: Klinikum der Universität Würzburg
state: Bayern
city: Elsterwerda
country: Germany
facility: Zentrum für Klinische Studien Südbrandenburg GmbH
state: Brandenburg
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)
state: Nordrhein-Westfalen
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: St. Vincenz und Elisabeth Hospital, Kathol. Klinikum Mainz
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: Klinische Forschung Dresden GmbH
state: Sachsen
city: Hamburg
country: Germany
facility: Cardiologicum Hamburg - Praxen Wandsbek
city: Kifisia / Athens
country: Greece
facility: KAT General Hospital of Athens
state: Attica
city: Athens
country: Greece
facility: G. GENNIMATAS General State Hospital of Athens
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Nea Ionia / Athens
country: Greece
facility: Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA
city: Thessaloniki
country: Greece
facility: "AHEPA" University General Hospital of Thessaloniki
city: Thessaloniki
country: Greece
facility: Hippokration General Hospital of Thessaloniki
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Korhaz
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz
city: Gyongyos
country: Hungary
facility: Pharma4Trial Kft.
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Hospital
city: Nyiregyhaza
country: Hungary
facility: Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.
city: Afula
country: Israel
facility: HaEmek Medical Center
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital Ein Kerem
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tiberias
country: Israel
facility: The Baruch Padeh Medical Center, Poria
city: Zefat
country: Israel
facility: Health Corporation of the Ziv Medical Center (R.A.)
city: Zrifin
country: Israel
facility: Shamir Medical Center (Assaf Harofeh)
city: Bologna
country: Italy
facility: A.O.U. di Bologna Policlinico S.Orsola Malpighi
state: Emilia-Romagna
city: Ferrara
country: Italy
facility: A.O.U. di Ferrara
state: Emilia-Romagna
city: Roma
country: Italy
facility: Asl Roma 6
state: Lazio
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
state: Lombardia
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
state: Lombardia
city: Milano
country: Italy
facility: IRCCS Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
state: Lombardia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Pavia
country: Italy
facility: IRCCS Fondazione Policlinico San Matteo
state: Lombardia
city: Sassari
country: Italy
facility: A.O.U. di Sassari
state: Sardegna
city: Matsudo
country: Japan
facility: Seikeikai New Tokyo Heart Clinic
state: Chiba
city: Kitakyushu
country: Japan
facility: Steel Memorial Yawata Hospital
state: Fukuoka
city: Sapporo
country: Japan
facility: Matsuda Cardiovascular clinic
state: Hokkaido
city: Kobe
country: Japan
facility: National Hospital Organization Kobe Medical Center
state: Hyogo
city: Takarazuka
country: Japan
facility: Higashi Takarazuka Satoh Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
state: Ishikawa
city: Morioka
country: Japan
facility: Iwate Prefectural Central Hospital
state: Iwate
city: Uji
country: Japan
facility: Uji-Tokushukai Medical Center
state: Kyoto
city: Hirakata
country: Japan
facility: Hirakata kohsai Hospital
state: Osaka
city: Kishiwada
country: Japan
facility: Kishiwada Tokushukai Hospital
state: Osaka
city: Takatsuki
country: Japan
facility: Takatsuki Red Cross Hospital
state: Osaka
city: Takatsuki
country: Japan
facility: Osaka Medical College Hospital
state: Osaka
city: Hamada
country: Japan
facility: National Hospital Organization Hamada Medical Center
state: Shimane
city: Hachioji
country: Japan
facility: Minamino Cardiovascular Hospital
state: Tokyo
city: Ota-ku
country: Japan
facility: Toho University Omori Medical Center
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo
city: Iwakuni
country: Japan
facility: National Hospital Organization Iwakuni Clinical Center
state: Yamaguchi
city: Fukui
country: Japan
facility: Fukui Prefectural Hospital
city: Okayama
country: Japan
facility: Okayama Rosai Hospital
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Toyama
country: Japan
facility: Toyama Prefectural Central Hospital
city: Kelantan
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
city: Kuala Lumpur
country: Malaysia
facility: Institute Jantung Negara
city: Sarawak
country: Malaysia
facility: Sarawak Heart Centre
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Bydgoszcz
country: Poland
facility: 10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ
city: Katowice
country: Poland
facility: CLINICAL MEDICAL RESEARCH Sp. z o. o.
city: Lodz
country: Poland
facility: SPZOZ Centralny Szpital Kliniczny UM w Lodzi
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecinskie Centrum Medyczne
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego UM
city: Wroclaw
country: Poland
facility: IV Wojskowy Szpital Kliniczny z Poliklinika, SPZOZ
city: Wroclaw
country: Poland
facility: Dolnoslaski Szp. Spec. im T.M. Centrum Medycyny Ratunkowej
city: Alcabideche
country: Portugal
facility: Hospital de Cascais
state: Lisboa
city: Guilhufe
country: Portugal
facility: CHTS - Hospital Padre Americo
state: Porto
city: Setubal
country: Portugal
facility: CHS - Hospital Sao Bernardo
state: Setúbal
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Lisboa
country: Portugal
facility: CHLO - Hospital Sao Francisco Xavier
city: Lisboa
country: Portugal
facility: Hospital da Luz - Lisboa
city: Porto
country: Portugal
facility: CHUP - Hospital Santo Antonio
city: Kemerovo
country: Russian Federation
facility: Sci-Res. Institute of Complex Cardiovascular Disorders
city: Moscow
country: Russian Federation
facility: Research center of therapy and prophylactic medicine
city: Moscow
country: Russian Federation
facility: Moscow State University n.a. M.V. Lomonosov
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Cardiology Dispensary n.a. Polyakov
city: St. Petersburg
country: Russian Federation
facility: City hospital #15
city: St. Petersburg
country: Russian Federation
facility: City Pokrovskaya Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: National Heart Centre Singapore
city: Pretoria
country: South Africa
facility: Clinical Trial Systems
state: Gauteng
city: Durban
country: South Africa
facility: Durban Medical Centre
state: Kwazulu-Natal
city: Merebank
country: South Africa
facility: Nash Ranjith Research Centre
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: TREAD Research cc
state: Western Cape
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre
state: Western Cape
city: Somerset West
country: South Africa
facility: Vergelegen Medi-Clinic
state: Western Cape
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
state: A Coruña
city: L'Hospitalet de Llobregat
country: Spain
facility: Ciutat Sanitària i Universitària de Bellvitge
state: Barcelona
city: Sant Joan Despi
country: Spain
facility: Hospital Sant Joan Despi Moises Broggi
state: Barcelona
city: Aravaca
country: Spain
facility: Hospital Sanitas La Zarzuela
state: Madrid
city: Majadahonda
country: Spain
facility: Hospital Universitario Clinica Puerta de Hierro
state: Madrid
city: Babio - Beade
country: Spain
facility: Hospital Álvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Sevilla
country: Spain
facility: Complejo Hospitalario Ntra. Sra. de Valme
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Cheng Hsin General Hospital
Study officials:
References:
citation: 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.
citation: 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.