Effect at 3 Months of Early Empagliflozin Initiation in Cardiogenic Shock Patients on Mortality, Rehospitalization, Left Ventricular Ejection Fraction and Renal Function.

NCT05879276 | Recruiting Phase 3 DMC

• 1 other identifier: 2023PI223 - 2023-503602-37-00
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 8

Brief Summary

Long term prognosis of cardiogenic shock is related to the resolution of haemodynamic failure, associated visceral failure and the recovery of an adequate myocardial function. In the immediate aftermath of cardiogenic shock, after catecholamines weaning, there are no recommendations on cardiovascular treatments that would improve this long term prognosis. Indeed, the standard cardiovascular treatments such as inhibitors of the renin-angiotensin and aldosterone system and beta-blockers have hypotensive and negative inotropic effects and may worsen the renal function. In practice, given their side effects, they are not prescribed in the immediate aftermath of cardiogenic shock. Sodium-glucose co-transporter 2 (iSGLT2) inhibitors are now an integral part of the drug management of chronic heart failure and the EMPULSE-HF trial has just demonstrated a benefit in acute heart failure (PMID: 35228754). Several pivotal clinical trials have demonstrated a significant effect of iSGLT2 on the survival and the risk of re hospitalisation for heart failure (PMID: 32865377, 31535829, 33200892). Our hypothesis is that, in patients in cardiogenic shock, early treatment with Empaglifozin in addition to the standard management could reduce mortality and morbidity (death, transplantation/LVAD and rehospitalisation for heart failure) and improve myocardial function at 12 weeks, compared with standard management alone.

Conditions

Cardiogenic Shock

Keywords

Heart failure; Acute heart failure; Cardiogenic shock; SGLT2 inhibitor; Mortality

Outcome Measures

Primary Outcomes (5)

• Time to all-cause death

  To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on composite endpoint components: 1. All-cause mortality or heart transplantation or ventricular assist, 2. Rehospitalization for heart failure, 3. Left ventricular ejection fraction. Hierarchical composite endpoint, assessed at 12 weeks from randomization (win-ratio method): * Rank 1: Time to all-cause death or cardiac transplantation or mechanical ventricular assist, * Rank 2: Time to rehospitalization for heart failure, * Rank 3: Left ventricular ejection fraction assessed during a research cardiac ultrasound.

  12-week after randomisation

• Time to cardiac transplantation

  To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on composite endpoint components: 1. All-cause mortality or heart transplantation or ventricular assist, 2. Rehospitalization for heart failure, 3. Left ventricular ejection fraction. Hierarchical composite endpoint, assessed at 12 weeks from randomization (win-ratio method): * Rank 1: Time to all-cause death or cardiac transplantation or mechanical ventricular assist, * Rank 2: Time to rehospitalization for heart failure, * Rank 3: Left ventricular ejection fraction assessed during a research cardiac ultrasound.

  12-week after randomisation

• Time to mechanical ventricular assist

  To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on composite endpoint components: 1. All-cause mortality or heart transplantation or ventricular assist, 2. Rehospitalization for heart failure, 3. Left ventricular ejection fraction. Hierarchical composite endpoint, assessed at 12 weeks from randomization (win-ratio method): * Rank 1: Time to all-cause death or cardiac transplantation or mechanical ventricular assist, * Rank 2: Time to rehospitalization for heart failure, * Rank 3: Left ventricular ejection fraction assessed during a research cardiac ultrasound.

  12-week after randomisation

• Time to rehospitalization for heart failure.

  To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on composite endpoint components: 1. All-cause mortality or heart transplantation or ventricular assist, 2. Rehospitalization for heart failure, 3. Left ventricular ejection fraction. Hierarchical composite endpoint, assessed at 12 weeks from randomization (win-ratio method): * Rank 1: Time to all-cause death or cardiac transplantation or mechanical ventricular assist, * Rank 2: Time to rehospitalization for heart failure, * Rank 3: Left ventricular ejection fraction assessed during a research cardiac ultrasound.

  12-week after randomisation

• Left ventricular ejection fraction assessed by cardiac ultrasound.

  To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on composite endpoint components: 1. All-cause mortality or heart transplantation or ventricular assist, 2. Rehospitalization for heart failure, 3. Left ventricular ejection fraction. Hierarchical composite endpoint, assessed at 12 weeks from randomization (win-ratio method): * Rank 1: Time to all-cause death or cardiac transplantation or mechanical ventricular assist, * Rank 2: Time to rehospitalization for heart failure, * Rank 3: Left ventricular ejection fraction assessed during a research cardiac ultrasound.

  12-week after randomisation

Secondary Outcomes (16)

• Death

  12-week after randomisation

• Heart transplantation or long-term ventricular assistance

  12-week after randomisation

• Rehospitalization for heart failure

  from hospital discharge to 12-week after randomisation

• Left ventricular ejection fraction assessed by cardiac ultrasound.

  12-week after randomisation

• E' wave assessed by cardiac ultrasound

  12-week after randomisation

Study Arms (2)

Empaglifozin in addition to standard management

EXPERIMENTAL

Patients in cardiogenic shock receiving empagliflozin in addition to standard management at a dose of 10 mg per day per os (or through nasogastric tube in intubated patients) for a duration of 12 weeks

Drug: Empagliflozin 10 MG

Standard management

NO INTERVENTION

Patients in cardiogenic shock receiving a standard management. SGLT2 inhibitor, which are now standard of care in chronic heart failure, in the strict respect of their indications, could be prescribed in the standard management group after hospitalization discharge.

Interventions

Empagliflozin 10 MG DRUG

Patients in cardiogenic shock receiving empagliflozin in addition to standard management at a dose of 10 mg per day per os (or through nasogastric tube in intubated patients) for a duration of 12 weeks.

Empaglifozin in addition to standard management

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients hospitalized in critical cardiac unit care or Intensive care unit for a cardiogenic shock
• "Who must have been or is on catecholamines for at least 12 hours for the treatment of cardiogenic shock.
• Patients who are able to take oral tablets

You may not qualify if:

• GFR\< 20 ml/min/1.73m2.
• Chronic dialysis.
• Patient on SGLT2 inhibitors prior to admission to ICU or CCU.
• Known allergy to SGLT2 inhibitors or to any of its excipients (in particular, patients with hereditary disorders of galactose intolerance, total lactase deficiency or glucose or galactose malabsorption syndrome)
• Patients on lithium.
• Patient in shock for another cause or moribund (SAPS2\> 90).
• Specific cardiogenic shock context:
• cardiac transplant patient or on transplant list.
• peripartum, adrenergic, valvular, non ischemic, post embolic heart disease.
• related to cardiotropic drug intoxication.
• Women of childbearing age without effective contraception.
• Person referred to in Articles 10, 31, 32, 33 and 34 of EU Regulation 536/2014 (Pregnant woman, parturient or breastfeeding mother, Minor (not emancipated), Adult person subject to a legal protection measure (guardianship, curatorship, safeguard of justice))

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (8)

CHR Metz - Thionville

Ars-Laquenexy, 57000, France

RECRUITING

CHU de Besançon

Besançon, 25000, France

RECRUITING

CHU de Dijon Bourgogne

Dijon, 21000, France

NOT YET RECRUITING

CHU Lille

Lille, 59000, France

NOT YET RECRUITING

CHU Reims

Reims, 51000, France

NOT YET RECRUITING

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67000, France

RECRUITING

CHRU de NANCY - réanimation médicale

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

Chru Nancy - Usic

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

MeSH Terms

Conditions

Shock, Cardiogenic; Heart Failure

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Study Officials

• Nicolas GIRERD, MD PhD

  CHRU of NANCY

  STUDY CHAIR

Central Study Contacts

Antoine KIMMOUN, MD PhD

CONTACT

3 83 15 40 79; a.kimmoun@chru-nancy.fr

Dany JANAH, MD

CONTACT

3 20 44 59 62; dany.janah@chu-lille.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: coordinating investigator

Model Details: Multicentre, interregional, randomised, controlled, open-label clinical trial evaluating the effect of early initiation of a SGLT2 inhibitor i.e Empaglifozin, in cardiogenic shock.

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: May 30, 2023
• Study Start: December 16, 2024
• Primary Completion (Estimated): March 16, 2027
• Study Completion (Estimated): March 16, 2027
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

FR (8)