Clinical trial NCT06439069: BMI-Driven Tolerability and Efficacy of Entresto in Heart Failure Patients
Official title: BMI-Driven Tolerability and Efficacy of Entresto in Heart Failure Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure
Obesity
Keywords: Heart failure
Entresto
Obese
Sacubitril/Valsartan
BMI
Tolerability
Efficacy
NT-proBNP
Lead sponsor: Lithuanian University of Health Sciences
Sponsor class: OTHER
Collaborators: name: Sligo General Hospital
name: KlaipÄ-da University
First posted: 2024-06-03
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study includes adult patients diagnosed with heart failure with reduced ejection fraction (HFrEF) and left ventricular ejection fraction (LVEF) ≤ 40%. Participants are either naïve to Entresto therapy or willing to switch from previous ACE inhibitor/ARB therapy. They will be categorized into four BMI groups: Normal Weight (BMI 18.5-24.9), Overweight (BMI 25-29.9), Obese (BMI 30-34.9), and Very Obese (BMI ≥ 35). Exclusion criteria include severe renal (eGFR \&lt; 30 mL/min/1.73m²) or hepatic impairment, history of angioedema, pregnancy, breastfeeding, active malignancies, severe comorbid conditions, and non-compliance with medication regimens. The study aims to enroll approximately 340 participants, with about 85 in each BMI category. Participants will be recruited from multiple cardiology clinics and hospitals.

Brief summary: This study aims to determine if patients with higher BMI can tolerate higher doses of Entresto (sacubitril/valsartan) and experience better symptomatic and functional outcomes compared to patients with lower BMI.

Detailed description: This prospective cohort study will enroll heart failure patients with reduced ejection fraction (HFrEF) to evaluate the tolerability and efficacy of Entresto uptitration across different BMI categories (Normal weight, Overweight, Obese, and Very Obese). Primary outcomes include the maximum tolerable dose and incidence of adverse drug reactions. Secondary outcomes include changes in heart failure symptoms, functional capacity measured by the 6-minute walk test, hospitalization rates, and mortality.

Eligibility criteria: Inclusion Criteria:

* Adults aged 18 and older
* Diagnosed with heart failure with reduced ejection fraction (HFrEF) (LVEF ≤ 35%)
* Naïve to Entresto therapy or willing to switch from previous ACE inhibitor/ARB therapy
* Ability to provide informed consent

Exclusion Criteria:

* Severe renal or hepatic impairment (e.g., eGFR \&lt; 30 mL/min/1.73m², severe liver disease)
* History of angioedema
* Pregnant or breastfeeding women
* Patients with malignancies or other severe comorbid conditions
* Non-compliance with medication regimen

Primary outcomes:
measure: Maximum tolerable dose of Entresto achieved
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Changes in Heart Failure Symptoms (NYHA Classification)
timeFrame: up to 24 weeks
measure: Changes in Functional Capacity (6-Minute Walk Test Distance)
timeFrame: up to 24 weeks
measure: Changes in Quality of Life (KCCQ Score)
timeFrame: up to 24 weeks
measure: Hospitalization Rates
timeFrame: up to 24 weeks
measure: Changes in BNP/NT-proBNP Levels
timeFrame: up to 24 weeks
Other outcomes:
Locations:
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
Study officials:
References: