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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Drug: Empagliflozin 10 MG

• Study Type: Interventional
• Enrollment (Estimated): 164
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Antoine KIMMOUN, MD PhD; Phone Number: +33 3 83 15 40 79; Email: a.kimmoun@chru-nancy.fr
• Study Contact Backup: Name: Dany JANAH, MD; Phone Number: +33 3 20 44 59 62; Email: dany.janah@chu-lille.fr

Study Locations

• France
  • Ars-Laquenexy, France, 57000
    • CHR Metz - Thionville
    • Contact: Guillaume LOUIS, MD
    • Principal Investigator: Guillaume LOUIS, MD
  • Besançon, France, 25000
    • CHU de Besancon
    • Contact: Gilles CAPELLIER, Md PhD
    • Principal Investigator: Gilles CAPELLIER, MD PhD
  • Dijon, France, 21000
    • CHU de Dijon Bourgogne
    • Contact: Jean Pierre QUENOT, MD
    • Principal Investigator: Jean Pierre QUENOT, MD PhD
  • Lille, France, 59000
    • CHU Lille
    • Contact: Dany JANAH, MD
    • Principal Investigator: Dany JANAH, MD
  • Reims, France, 51000
    • CHU Reims
    • Contact: Bruno MOURVILLIER, MD PhD
    • Principal Investigator: Bruno MOURVILLIER, MD PhD
  • Strasbourg, France, 67000
    • Hôpitaux Universitaires de Strasbourg
    • Contact: Ferhat MEZIANI, MD PhD
    • Principal Investigator: Ferhat MEZIANI, MD PhD
  • Vandœuvre-lès-Nancy, France, 54500
    • CHRU de Nancy
    • Contact: Antoine KIMMOUN, MD PhD; Email: a.kimmoun@chru-nancy.fr
    • Principal Investigator: Antoine KIMMOUN, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients hospitalized in critical cardiac unit care or Intensive care unit for a cardiogenic shock
• Patient on catecholamine for more than 12 hours and less than 5 days.

Exclusion Criteria:

• 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:

  1. cardiac transplant patient or on transplant list.
  2. peripartum, adrenergic, valvular, restrictive, post embolic heart disease.
  3. caused by a conduction/rhythm disorder of non-ischemic etiology.
  4. related to cardiotropic drug intoxication.
  5. secondary to a cardiocirculatory arrest with more than 25 min of "low flow" or more than 5 min of "no flow" before recovery of a stable cardiac activity.
• Patient undergoing VA-ECMO at admission (before or in whom implantation is imminent (less than 3 hours)).
• 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))

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empaglifozin in addition to standard management; 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; 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.
No Intervention: Standard management; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: All-cause mortality or heart transplantation or ventricular assist,; Rehospitalization for heart failure,; 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: All-cause mortality or heart transplantation or ventricular assist,; Rehospitalization for heart failure,; 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: All-cause mortality or heart transplantation or ventricular assist,; Rehospitalization for heart failure,; 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: All-cause mortality or heart transplantation or ventricular assist,; Rehospitalization for heart failure,; 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: All-cause mortality or heart transplantation or ventricular assist,; Rehospitalization for heart failure,; 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on all-cause mortality at 12 weeks from randomization	12-week after randomisation
Heart transplantation or long-term ventricular assistance	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on heart transplantation or long-term ventricular assistance, at 12 weeks from randomization	12-week after randomisation
Rehospitalization for heart failure	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on rehospitalization for heart failure, at 12 weeks from randomization	from hospital discharge to 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 left ventricular ejection fraction, at 12 weeks from randomization.	12-week after randomisation
E' wave assessed by cardiac ultrasound	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the left ventricular diastolic function and filling pressures, at 12 weeks from randomization.	12-week after randomisation
E/e' ratio assessed by cardiac ultrasound	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the left ventricular diastolic function and filling pressures, at 12 weeks from randomization.	12-week after randomisation
TAPSE assessed by cardiac ultrasound	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the right ventricular function, at 12 weeks from randomization	12-week after randomisation
S wave at the annular tricuspid level assessed by cardiac ultrasound	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the right ventricular function, at 12 weeks from randomization	12-week after randomisation
Renal replacement therapy	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the renal function, at 12 weeks from randomization	Randomisation and 12-week after randomisation
Renal function	The number of patients requiring renal replacement therapy between randomization and 12 weeks, and change in renal function assessed at baseline and 12 weeks: glomerular filtration rate calculated by the CKD-EPI method	Randomisation and 12-week after randomisation
Bilirubin	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the hepatic function, at 12 weeks from randomization	Randomisation and 12-week after randomisation
Prothrombin Ratio (PT)	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the hepatic function, at 12 weeks from randomization	Randomisation and 12-week after randomisation
SGOT	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the hepatic function, at 12 weeks from randomization	Randomisation and 12-week after randomisation
SGPT	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the hepatic function, at 12 weeks from randomization	Randomisation and 12-week after randomisation
NT-Pro-BNP	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the evolution of the hydro-sodic overload, at 12 weeks from randomization. The measure of NT-Pro-BNP will be measured at 12 weeks and delta from randomisation will be calculated	Randomisation and 12-week after randomisation
Weight	To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the evolution of the hydro-sodic overload, at 12 weeks from randomization. The weight will be measured at 12 weeks and delta from randomisation will be calculated	Randomisation and 12-week after randomisation

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Study Chair: Nicolas GIRERD, MD PhD, CHRU of Nancy

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: April 12, 2023
• First Submitted That Met QC Criteria: May 24, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Heart failure; Mortality; Acute heart failure; SGLT2 inhibitor; Cardiogenic shock
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 2023-503602-37-00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No