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

Primary Purpose

Cardiogenic Shock

Status
Not yet recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Empagliflozin 10 MG
Sponsored by
Central Hospital, Nancy, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiogenic Shock focused on measuring Heart failure, Acute heart failure, Cardiogenic shock, SGLT2 inhibitor, Mortality

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: cardiac transplant patient or on transplant list. peripartum, adrenergic, valvular, restrictive, post embolic heart disease. caused by a conduction/rhythm disorder of non-ischemic etiology. related to cardiotropic drug intoxication. 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))

Sites / Locations

  • CHR Metz - Thionville
  • CHU de Besançon
  • CHU de Dijon Bourgogne
  • CHU Lille
  • CHU Reims
  • Hôpitaux Universitaires de Strasbourg
  • CHRU de NANCY

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Empaglifozin in addition to standard management

Standard management

Arm Description

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

Patients in cardiogenic shock receiving a standard management. SGLT2 inhibitor, which are now standard of care in chronic heart failure, in the strict respect of their indications, could be prescribed in the standard management group after hospitalization discharge.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.

Secondary Outcome Measures

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
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
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
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.
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.
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.
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
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
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
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
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
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
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
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
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
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

Full Information

First Posted
April 12, 2023
Last Updated
May 24, 2023
Sponsor
Central Hospital, Nancy, France
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1. Study Identification

Unique Protocol Identification Number
NCT05879276
Brief Title
Effect at 3 Months of Early Empagliflozin Initiation in Cardiogenic Shock Patients on Mortality, Rehospitalization, Left Ventricular Ejection Fraction and Renal Function.
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
January 2026 (Anticipated)
Study Completion Date
January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Central Hospital, Nancy, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiogenic Shock
Keywords
Heart failure, Acute heart failure, Cardiogenic shock, SGLT2 inhibitor, Mortality

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
164 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Empaglifozin in addition to standard management
Arm Type
Experimental
Arm Description
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
Arm Title
Standard management
Arm Type
No Intervention
Arm Description
Patients in cardiogenic shock receiving a standard management. SGLT2 inhibitor, which are now standard of care in chronic heart failure, in the strict respect of their indications, could be prescribed in the standard management group after hospitalization discharge.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 10 MG
Intervention Description
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 Measure Information:
Title
Time to all-cause death
Description
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.
Time Frame
12-week after randomisation
Title
Time to cardiac transplantation
Description
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.
Time Frame
12-week after randomisation
Title
Time to mechanical ventricular assist
Description
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.
Time Frame
12-week after randomisation
Title
Time to rehospitalization for heart failure.
Description
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.
Time Frame
12-week after randomisation
Title
Left ventricular ejection fraction assessed by cardiac ultrasound.
Description
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.
Time Frame
12-week after randomisation
Secondary Outcome Measure Information:
Title
Death
Description
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
Title
Heart transplantation or long-term ventricular assistance
Description
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
Title
Rehospitalization for heart failure
Description
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
Title
Left ventricular ejection fraction assessed by cardiac ultrasound.
Description
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
Title
E' wave assessed by cardiac ultrasound
Description
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
Title
E/e' ratio assessed by cardiac ultrasound
Description
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
Title
TAPSE assessed by cardiac ultrasound
Description
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
Title
S wave at the annular tricuspid level assessed by cardiac ultrasound
Description
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
Title
Renal replacement therapy
Description
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
Title
Renal function
Description
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
Title
Bilirubin
Description
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
Title
Prothrombin Ratio (PT)
Description
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
Title
SGOT
Description
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
Title
SGPT
Description
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
Title
NT-Pro-BNP
Description
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
Title
Weight
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: cardiac transplant patient or on transplant list. peripartum, adrenergic, valvular, restrictive, post embolic heart disease. caused by a conduction/rhythm disorder of non-ischemic etiology. related to cardiotropic drug intoxication. 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))
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antoine KIMMOUN, MD PhD
Phone
3 83 15 40 79
Ext
+33
Email
a.kimmoun@chru-nancy.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Dany JANAH, MD
Phone
3 20 44 59 62
Ext
+33
Email
dany.janah@chu-lille.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas GIRERD, MD PhD
Organizational Affiliation
CHRU of NANCY
Official's Role
Study Chair
Facility Information:
Facility Name
CHR Metz - Thionville
City
Ars-Laquenexy
ZIP/Postal Code
57000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillaume LOUIS, MD
First Name & Middle Initial & Last Name & Degree
Guillaume LOUIS, MD
Facility Name
CHU de Besançon
City
Besançon
ZIP/Postal Code
25000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gilles CAPELLIER, Md PhD
First Name & Middle Initial & Last Name & Degree
Gilles CAPELLIER, MD PhD
Facility Name
CHU de Dijon Bourgogne
City
Dijon
ZIP/Postal Code
21000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean Pierre QUENOT, MD
First Name & Middle Initial & Last Name & Degree
Jean Pierre QUENOT, MD PhD
Facility Name
CHU Lille
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dany JANAH, MD
First Name & Middle Initial & Last Name & Degree
Dany JANAH, MD
Facility Name
CHU Reims
City
Reims
ZIP/Postal Code
51000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruno MOURVILLIER, MD PhD
First Name & Middle Initial & Last Name & Degree
Bruno MOURVILLIER, MD PhD
Facility Name
Hôpitaux Universitaires de Strasbourg
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ferhat MEZIANI, MD PhD
First Name & Middle Initial & Last Name & Degree
Ferhat MEZIANI, MD PhD
Facility Name
CHRU de NANCY
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54500
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine KIMMOUN, MD PhD
Email
a.kimmoun@chru-nancy.fr
First Name & Middle Initial & Last Name & Degree
Antoine KIMMOUN, MD PhD

12. IPD Sharing Statement

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

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