Clinical trial NCT05879276: Effect at 3 Months of Early Empagliflozin Initiation in Cardiogenic Shock Patients on Mortality, Rehospitalization, Left Ventricular Ejection Fraction and Renal Function.
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cardiogenic Shock
Keywords: Heart failure
Acute heart failure
Cardiogenic shock
SGLT2 inhibitor
Mortality
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2023-05-30
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, interregional, randomised, controlled, open-label clinical trial evaluating the effect of early initiation of a SGLT2 inhibitor i.e Empaglifozin, in cardiogenic shock.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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))

Primary outcomes:
measure: Time to all-cause death
timeFrame: 12-week after randomisation
measure: Time to cardiac transplantation
timeFrame: 12-week after randomisation
measure: Time to mechanical ventricular assist
timeFrame: 12-week after randomisation
measure: Time to rehospitalization for heart failure.
timeFrame: 12-week after randomisation
measure: Left ventricular ejection fraction assessed by cardiac ultrasound.
timeFrame: 12-week after randomisation
Secondary outcomes:
measure: Death
timeFrame: 12-week after randomisation
measure: Heart transplantation or long-term ventricular assistance
timeFrame: 12-week after randomisation
measure: Rehospitalization for heart failure
timeFrame: from hospital discharge to 12-week after randomisation
measure: Left ventricular ejection fraction assessed by cardiac ultrasound.
timeFrame: 12-week after randomisation
measure: E' wave assessed by cardiac ultrasound
timeFrame: 12-week after randomisation
measure: E/e' ratio assessed by cardiac ultrasound
timeFrame: 12-week after randomisation
measure: TAPSE assessed by cardiac ultrasound
timeFrame: 12-week after randomisation
measure: S wave at the annular tricuspid level assessed by cardiac ultrasound
timeFrame: 12-week after randomisation
measure: Renal replacement therapy
timeFrame: Randomisation and 12-week after randomisation
measure: Renal function
timeFrame: Randomisation and 12-week after randomisation
measure: Bilirubin
timeFrame: Randomisation and 12-week after randomisation
measure: Prothrombin Ratio (PT)
timeFrame: Randomisation and 12-week after randomisation
measure: SGOT
timeFrame: Randomisation and 12-week after randomisation
measure: SGPT
timeFrame: Randomisation and 12-week after randomisation
measure: NT-Pro-BNP
timeFrame: Randomisation and 12-week after randomisation
measure: Weight
timeFrame: Randomisation and 12-week after randomisation
Other outcomes:
Locations:
city: Ars-Laquenexy
country: France
facility: CHR Metz - Thionville
city: Besançon
country: France
facility: CHU de Besançon
city: Dijon
country: France
facility: CHU de Dijon Bourgogne
city: Lille
country: France
facility: CHU Lille
city: Reims
country: France
facility: CHU Reims
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU de NANCY
Study officials:
affiliation: CHRU of NANCY
name: Nicolas GIRERD, MD PhD
role: STUDY_CHAIR
References: