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

Cardiogenic Shock Clinical Trial

— EMPASHOCK  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05879276
• Other study ID #: 2023-503602-37-00
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 2023
• Est. completion date: January 2026

Study information

• Verified date: May 2023
• Source: Central Hospital, Nancy, France
• Contact: Antoine KIMMOUN, MD PhD
• Phone: 3 83 15 40 79
• Email: a.kimmoun[@]chru-nancy.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 164
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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))

Related Conditions & MeSH terms

• Cardiogenic Shock
• Shock
• Shock, Cardiogenic

Intervention

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.

Locations

Country	Name	City	State
France	CHR Metz - Thionville	Ars-Laquenexy
France	CHU de Besançon	Besançon
France	CHU de Dijon Bourgogne	Dijon
France	CHU Lille	Lille
France	CHU Reims	Reims
France	Hôpitaux Universitaires de Strasbourg	Strasbourg
France	CHRU de NANCY	Vandœuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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