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

Phase 3RecruitingNCT05879276

Central Hospital, Nancy, France164 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

164

Conditions

Cardiogenic Shock

Interventions

Empagliflozin 10 MGDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 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, non ischemic, post embolic heart disease. 3. related to cardiotropic drug intoxication. 4. Secondary to a cardiac arrest for which the patient remains comatose prior to inclusion. * 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))

Locations (8)

CHR Metz - Thionville

Ars-Laquenexy, France

RECRUITING

CHU de Besançon

Besançon, France

RECRUITING

CHU de Dijon Bourgogne

Dijon, France

NOT_YET_RECRUITING

CHU Lille

Lille, France

NOT_YET_RECRUITING

CHU Reims

Reims, France

NOT_YET_RECRUITING

Hôpitaux Universitaires de Strasbourg

Strasbourg, France

RECRUITING

CHRU de NANCY - réanimation médicale

Vandœuvre-lès-Nancy, France

RECRUITING

Chru Nancy - Usic

Vandœuvre-lès-Nancy, France

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 12-week after randomisation

Time to cardiac transplantation

Time frame: 12-week after randomisation

Time to mechanical ventricular assist

Time frame: 12-week after randomisation

Time to rehospitalization for heart failure.

Time frame: 12-week after randomisation

Left ventricular ejection fraction assessed by cardiac ultrasound.

Time frame: 12-week after randomisation

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 12-week after randomisation

E/e' ratio assessed by cardiac ultrasound

Time frame: 12-week after randomisation

Central 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

Data from ClinicalTrials.gov

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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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Randomisation and 12-week after randomisation