Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Chronic Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
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* Drug: Vericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tablets
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vericiguat up to 10 mg<br>Subjects 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. | Drug: Vericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tablets<br>* 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.<br>|
| Experimental: Vericiguat up to 15 mg<br>Subjects 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. | Drug: Vericiguat (BAY1021189) 2.5 mg, 5 mg or 10 mg IR tablets<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Subject will receive placebo for 24 weeks, once daily, starting sham up-titration at weeks 2, 4, and 6. | Drug: Placebo<br>* Placebo and sham up-titration at weeks 2, 4, and 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |