Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF
Condition: Chronic Heart Failure With Preserved Ejection Fraction
MeSH terms: Heart Failure
Intervention: Vericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tablets; Placebo
Intervention description: 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 and sham up-titration at weeks 2, 4, and 6
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 789.0
Sex: All
Minimum age: 45 Years
Healthy volunteers: No

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