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.

Elegibilidad

Edad mínima: 45 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

SBP \<110 mmHg and/or DBP \<40 mmHg and/or symptomatic hypotension
Resting heart rate (HR) \<50 or ≥100 beats per minute (bpm)
Clinical instability at randomization, defined by
Any IV treatment within 24h prior to randomization, and/or
SBP ≥160 mmHg
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

Intervenciones

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.

drug

Placebo

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

Ubicaciones

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

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)

Resumen