Clinical trial NCT05556044: Empagliflozin for New On-set Heart Failure Study Regardless of Ejection Fraction
Official title: In-hospital Initiation of Empagliflozin for the Treatment of New-onset Acute Heart Failure Regardless of Ejection Fraction: A Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Heart Failure
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-09-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Heart failure (HF) is one of the most important reasons for hospital admission and is associated with high mortality and morbidity. After discharge, up to 40% of patients are readmitted within 6 months and 1-year post-discharge mortality is high. The cost burden of treating patients with HF is high and \~80% of healthcare costs are related to hospital admissions.

Sodium-glucose cotransporter-2 (SGLT2) inhibitor is considered one of the four foundational therapies (ACE-I or ARNI, beta-blockers, MRA, and SGLT2 inhibitors) for HFrEF. In particular, empagliflozin has been shown in randomized controlled trials to reduce the combined risk of cardiovascular death or HF hospitalization in HF patients with both reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, guidelines do not specify the sequence and the timing of which therapy to be commenced. The timing of SGLT inhibitors initiation in the treatment of acute HF is not established. In particular, new-onset acute HF is a group which is understudied in the major trials to date. This study aims to evaluate the efficacy and safety of in-hospital initiation of empagliflozin in patients hospitalized for new onset acute HF, regardless of LVEF for up to 90 days of follow-up.


Eligibility criteria: Inclusion Criteria:

* Subject age \>18 hospitalized for primary diagnosis of acute HF
* Dyspnoea (exertional or at rest) and 2 of the following signs: Congestion on chest X-ray; Rales on chest auscultation; Clinically relevant oedema (e.g. ≥1+ on a 0 to 3+ scale); Elevated jugular venous pressure
* Stabilization criteria (while in the hospital): systolic blood pressure ≥100mmHg and no symptoms of hypotension in the preceding 24 hours; No increase in i.v. diuretic dose for 24 h prior; No i.v. vasodilators including nitrates within the last 24 h prior; No i.v. inotropic drugs for 24 h prior
* NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL. (Patients with atrial fibrillation: NT-proBNP ≥2400 pg/mL or BNP

  ≥600 pg/mL. Measured during index hospitalization
* Heart failure hospitalization that requires the treatment of a minimum single dose of 40 mg of i.v.

furosemide( or Equivalent i.v loop diuretics defined as 20 mg of torsemide or 1mg of bumetanide)

Exclusion Criteria:

* Cardiogenic shock
* Documented history of HF with previous HF admission
* Current hospitalization for acute HF primarily triggered by pulmonary embolism, cerebrovascular accident, or acute myocardial infraction
* Interventions in the past 30 days prior or planned during the study: Major cardiac surgery, or Transcatheter aortic valve implantation (TAVI), or percutaneous coronary intervention (PCI), or MitraClip; Implantation of cardiac resynchronization therapy device; Cardiac mechanical support implantation
* Current or expected heart transplant, left ventricular assist device (LVAD), intraaortic balloon pumping (IABP), or patients with planned inotropic support in an outpatient setting
* Haemodynamically severe uncorrected primary cardiac valvular disease planned for surgery or intervention during the course of the study
* eGFR \<20 mL/min/1.73m2 as measured during index hospitalization (latest measurement before randomization) or patients requiring dialysis
* Type 1 diabetes mellitus (DM)
* History of ketoacidosis, including diabetic ketoacidosis
* Current or prior treatment with SGLT2 inhibitors in the 90 days prior to enrolment.

Primary outcomes:
measure: Heart failure (HF) events
timeFrame: 90 days
measure: All-cause mortality
timeFrame: 90 days
Secondary outcomes:
measure: Change in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS)
timeFrame: 90 days
measure: NT-proBNP level
timeFrame: 90 days
measure: New York Heart Association (NYHA) class
timeFrame: 90 days
measure: Major Adverse Cardiovascular Event (MACE)
timeFrame: 90 days
measure: Occurrence of kidney damage
timeFrame: 90 days
measure: Weight loss
timeFrame: 90 days
measure: Quality-adjusted life years (QALY) gained
timeFrame: 90 days
measure: Change in 6 minute hall walk (6MHW)
timeFrame: 90 days
Other outcomes:
Locations:
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Bryan Yan
role: PRINCIPAL_INVESTIGATOR
References: