SGLT2 Inhibitors in Patients With ADHF During Ventilator Weaning

Sponsor

National Taiwan University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT06142474

Collaborator

(none)

450

Enrollment

Location

Arms

Anticipated Duration (Months)

4.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Acute Ventilator Lung	Drug: SGLT2 inhibitor	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

450 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Potential Beneficial Effects of SGLT2 Inhibitors in Patients With Acute Decompensated Heart Failure During Ventilator Weaning: a Prospective Multicenter Cohort Study.

Actual Study Start Date :

Oct 10, 2022

Anticipated Primary Completion Date :

Oct 9, 2030

Anticipated Study Completion Date :

Oct 9, 2030

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: acute decompensated HF Patients acute decompensated HF Patients 2：1，have 50 Patients control and 100 Patients randomly assigned empagliflozin or dapagliflozin
Experimental: 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	Drug: SGLT2 inhibitor 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 Other Names: Empagliflozin and dapagliflozin
Experimental: 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	Drug: SGLT2 inhibitor 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 Other Names: Empagliflozin and dapagliflozin

Arm

Intervention/Treatment

No Intervention: acute decompensated HF Patients

acute decompensated HF Patients 2：1，have 50 Patients control and 100 Patients randomly assigned empagliflozin or dapagliflozin

Experimental: 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

Drug: SGLT2 inhibitor

Other Names:

Empagliflozin and dapagliflozin

Experimental: dapagliflozin 10mg

Drug: SGLT2 inhibitor

Other Names:

Empagliflozin and dapagliflozin

Outcome Measures

Primary Outcome Measures

Composite of weaning failure, recurrent pulmonary edema, and cardiovascular/non-cardiovascular mortality. [90 days]
Weaning failure is defined that patient is reintubated within 7 days following extubation, irrespective of the use of noninvasive ventilation

Secondary Outcome Measures

Components of the primary endpoint [90 days]
Weaning failure, recurrent pulmonary edema, and cardiovascular/non-cardiovascular mortality.
Diuretic response [after 15 and 30 days of treatment]
Any poor response to diuretics
Change in NT-proBNP level [over 30 days of treatment]
Difference between 30 days and baseline
Occurrence of chronic dialysis or renal transplant or significant, sustained reduction of estimated glomerular filtration rate [90 days]
Dialysis, renal transplant and eGFR
The therapeutic effect by different SGLT2i on components of the primary endpoint. [90 days]
Empagliflozin vs Dapagliflozin

Other Outcome Measures

Safety parameters [30 days]
Markers of volume depletion, hypotension and acute renal failure

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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:

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