The Potential Beneficial Effects of SGLT2 Inhibitors in Patients With Acute Decompensated Heart Failure During Ventilator Weaning: a Prospective Multicenter Cohort Study.
Overview
- Phase
- Phase 3
- Intervention
- SGLT2 inhibitor
- Conditions
- Heart Failure Acute
- Sponsor
- National Taiwan University Hospital
- Enrollment
- 450
- Locations
- 1
- Primary Endpoint
- Composite of weaning failure, recurrent pulmonary edema, and cardiovascular/non-cardiovascular mortality.
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This study will explore the potential benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in preventing cardiac ischemia and cardiopulmonary edema in patients with acute decompensated heart failure during weaning from ventilators.
Detailed Description
Patients with acute decompensated HF will be open-label randomly assigned to be treated with or without SGLT2 inhibitors (either empagliflozin 10 mg once daily or dapagliflozin 10 mg once daily) 3 days before ventilator weaning in a ratio of 2:1. If the patients are allocated to SGLT2i treatment group, they will be further randomized equally to either empagliflozin- or dapagliflozin-treated group. A series of examination will be performed to detect weaning-induced cardiac ischemia and weaning-induced cardiopulmonary edema, including electrocardiography, chest X-ray, echocardiography, and biomarkers. Echocardiography Transthoracic echocardiography (TTE) will be performed by a trained operator at several time points: (1) before SBT and SGLT2i initiation; (2) during SBT trial just after initiating SGLT2 inhibitor; (3) during SBT trial 3 days after initiation of SGLT2 inhibitor; (4) within 24 hrs after extubation; (5) 7-10 days after extubation; (6) 90±7 days after extubation. Biomarkers NT-proBNP, plasma protein, high-sensitive cardiac troponin T, and hemoglobin level will be checked at several time points: (1) before spontaneous breathing trial (SBT), (2) during SBT trial (at least 10 mins after the initiation of SBT) just after initiating SGLT2 inhibitor; (3) during SBT (at least 10 mins after the initiation of SBT) trial 3 days after SGLT2 inhibitor; (4) within 24 hrs after extubation; (5) 7\~10 days after extubation; (5) 90±7 days after extubation. We will also check arterial blood gas analyses at the end of SBT trial just after initiating SGLT2 inhibitor and 3 days after SGLT2 inhibitor.
Investigators
National Taiwan University Clinical Trial Center
Chih Fan Yeh, MD, PhD
National Taiwan University Hospital
Eligibility Criteria
Inclusion Criteria
- •Patients aged ≥20 years
- •Currently hospitalized for the primary diagnosis of acute HF (de novo or decompensated chronic HF) in HFrEF patients (LVEF≤40%)
- •Meet the stabilization criteria:
- •A. Systolic BP ≥100mm Hg and no symptoms of hypotension in the preceding 6 hours B. No increase in i.v. diuretic dose for 6 hours prior to randomization C. No i.v. vasodilators including nitrates within the last 6 hours prior to randomization D. No i.v. inotropic drugs for 24 hours prior to randomization
- •Elevated N-terminal proB-type natriuretic peptide (NT-proBNP) or BNP:
- •A. Without atrial fibrillation (AF): NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL B. With AF: NT-proBNP ≥2400 pg/mL or BNP ≥600 pg/mL
- •Patients were intubated for at least 24 hour with ventilator settings allowing to initiate the weaning process \[SpO2 \> 90% or PaO2/FiO2 ≥ 150 mmHg with a fraction of inspired oxygen (FiO2) ≤ 40% and a positive end-expiratory pressure (PEEP) ≤ 8 cmH2O\].
Exclusion Criteria
- •Decision to withdraw life support
- •Cardiogenic shock
- •Hospitalization for HF (HHF) triggered by acute myocardial infarction (AMI) or pulmonary embolism
- •Planned or previous (within 30 days) cardiovascular revascularization or major cardiac surgery/intervention/device implantation
- •Prior acute coronary syndrome, AMI, stroke or transient ischemic accident within 90 days
- •Estimated glomerular filtration rate (eGFR) of less than 30 ml per minute per 1.73 m2 of body-surface area
- •Type 1 diabetes mellitus
- •Poorly controlled type 2 diabetes mellitus (a glycated hemoglobin level above 10.5%)
- •Uncontrolled urinary tract infection
Arms & Interventions
empagliflozin 10mg
acute decompensated HF Patients 2：1,have 50 Patients control and 100 Patients randomly assigned empagliflozin or dapagliflozin ,3 days before ventilator weaning in a ratio of 1:1.empagliflozin 10 mg once daily
Intervention: SGLT2 inhibitor
dapagliflozin 10mg
acute decompensated HF Patients 2：1,have 50 Patients control and 100 Patients randomly assigned empagliflozin or dapagliflozin ,3 days before ventilator weaning in a ratio of 2:1. dapagliflozin 10 mg once daily
Intervention: SGLT2 inhibitor
Outcomes
Primary Outcomes
Composite of weaning failure, recurrent pulmonary edema, and cardiovascular/non-cardiovascular mortality.
Time Frame: 90 days
Weaning failure is defined that patient is reintubated within 7 days following extubation, irrespective of the use of noninvasive ventilation
Secondary Outcomes
- Components of the primary endpoint(90 days)
- Diuretic response(after 15 and 30 days of treatment)
- Change in NT-proBNP level(over 30 days of treatment)
- Occurrence of chronic dialysis or renal transplant or significant, sustained reduction of estimated glomerular filtration rate(90 days)
- The therapeutic effect by different SGLT2i on components of the primary endpoint.(90 days)