Cardiogenic Shock
Conditions
Keywords
Heart failure, Acute heart failure, Cardiogenic shock, SGLT2 inhibitor, Mortality
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.
Interventions
DRUGEmpagliflozin 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.
Sponsors
Central Hospital, Nancy, France
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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))
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to all-cause death | 12-week after randomisation | 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 to cardiac transplantation | 12-week after randomisation | 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 to mechanical ventricular assist | 12-week after randomisation | 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 to rehospitalization for heart failure. | 12-week after randomisation | 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. |
| Left ventricular ejection fraction assessed by cardiac ultrasound. | 12-week after randomisation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| E/e' ratio assessed by cardiac ultrasound | 12-week after randomisation | 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. |
| TAPSE assessed by cardiac ultrasound | 12-week after randomisation | 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 |
| S wave at the annular tricuspid level assessed by cardiac ultrasound | 12-week after randomisation | 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 |
| Renal replacement therapy | Randomisation and 12-week after randomisation | 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 |
| Renal function | Randomisation and 12-week after randomisation | 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 |
| Death | 12-week after randomisation | 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 |
| Prothrombin Ratio (PT) | Randomisation and 12-week after randomisation | 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 |
| SGOT | Randomisation and 12-week after randomisation | 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 |
| SGPT | Randomisation and 12-week after randomisation | 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 |
| NT-Pro-BNP | Randomisation and 12-week after randomisation | 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 |
| Weight | Randomisation and 12-week after randomisation | 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 |
| Bilirubin | Randomisation and 12-week after randomisation | 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 |
| Heart transplantation or long-term ventricular assistance | 12-week after randomisation | 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 |
| Rehospitalization for heart failure | from hospital discharge to 12-week after randomisation | 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 |
| Left ventricular ejection fraction assessed by cardiac ultrasound. | 12-week after randomisation | 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. |
| E' wave assessed by cardiac ultrasound | 12-week after randomisation | 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. |
Countries
France
Contacts
Primary ContactAntoine KIMMOUN, MD PhD
Backup ContactDany JANAH, MD
Outcome results
None listed