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

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.

Interventions

• 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.

Primary outcome measures

• Time to all-cause death [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 outcome measures (12)

• Death [Time frame: 12-week after randomisation]
• Heart transplantation or long-term ventricular assistance [Time frame: 12-week after randomisation]
• Rehospitalization for heart failure [Time frame: from hospital discharge to 12-week after randomisation]
• Left ventricular ejection fraction assessed by cardiac ultrasound. [Time frame: 12-week after randomisation]
• E' wave assessed by cardiac ultrasound [Time frame: 12-week after randomisation]
• E/e' ratio assessed by cardiac ultrasound [Time frame: 12-week after randomisation]
• TAPSE assessed by cardiac ultrasound [Time frame: 12-week after randomisation]
• S wave at the annular tricuspid level assessed by cardiac ultrasound [Time frame: 12-week after randomisation]
• Renal replacement therapy [Time frame: Randomisation and 12-week after randomisation]
• Renal function [Time frame: Randomisation and 12-week after randomisation]
• Bilirubin [Time frame: Randomisation and 12-week after randomisation]
• Prothrombin Ratio (PT) [Time frame: Randomisation and 12-week after randomisation]

Eligibility criteria

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:

• cardiac transplant patient or on transplant list.
• peripartum, adrenergic, valvular, non ischemic, post embolic heart disease.
• related to cardiotropic drug intoxication.
• 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))

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 8 centers

• CHR Metz - Thionville — Ars-Laquenexy
• CHU de Besançon — Besançon
• CHU de Dijon Bourgogne — Dijon
• CHU Lille — Lille
• CHU Reims — Reims
• Hôpitaux Universitaires de Strasbourg — Strasbourg
• CHRU de NANCY - réanimation médicale — Vandœuvre-lès-Nancy
• Chru Nancy - Usic — Vandœuvre-lès-Nancy

Identifiers

NCT: NCT05879276 · 2023PI223 - 2023-503602-37-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗