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 ( EMPASHOCK )

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CHRU De Nancy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

16 Dec 2024 → ongoing

Decision date (initial)

2024-04-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

French Ministry of Health (PHRC IR 2021)

External identifiers

EU CT number

2023-503602-37-00

ClinicalTrials.gov

NCT05879276

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the effect of early introduction of empagliflozin in addition to usual management versus usual management alone at 12 weeks on a hierarchical composite morbidity endpoint including all-cause death or transplantation or long-term mechanical assistance or rehospitalization for heart failure and left ventricular ejection fraction.

Secondary objectives 9

1. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on all-cause mortality.
2. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the number of heart transplants or the number of long-term ventricular assistance
3. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on the number of rehospitalizations for heart failure
4. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone on left ventricular ejection fraction
5. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone at 12 weeks on left ventricular diastolic function and filling pressures,
6. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone at 12 weeks on the right ventricular function,
7. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone at 12 weeks on renal function,
8. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone at 12 weeks on hepatic function,
9. To compare the effect of early introduction of empagliflozin in addition to standard management versus standard management alone at 12 weeks on the evolution of the hydro-sodic overload.

Conditions and MedDRA coding

Cardiogenic Shock

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Adult patients ≥18 years old hospitalized in critical cardiac unit care or Intensive care unit for a cardiogenic shock
2. Who must have been or is under catecholamine for at least 12 hours for the treatment of cardiogenic shock. The definition of cardiogenic shock is as follows, adapted from the SHARC expert consensus: it refers to a patient with cardiac dysfunction resulting in a systolic blood pressure lower than 90 mmHg for at least 30 minutes (or requiring the use of vasopressors, inotropes, or mechanical circulatory support to maintain a systolic blood pressure of at least 90 mmHg) with evidence of hypoperfusion (≥ 1): •Elevated arterial lactate (>2 mmol/L), • Acute renal failure (creatinine ≥ 2x the upper normal limit) or oliguria (e.g., urine output <0.5 mL/kg/h), • Acute liver failure (e.g., AST and/or ALT > 3x the upper normal limit), • Cold extremities or mottling or capillary refill time (CRT) ≥ 3 seconds, •Altered consciousness unexplained by another cause.
3. Person affiliated to a social security scheme

Exclusion criteria 10

1. GFR< 20 ml/min/1.73m2.
2. Women of childbearing age without effective contraception
3. Type 1 diabete patient
4. 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))
5. Chronic dialysis
6. Patient on SGLT2 inhibitors prior to admission to intensive care unit or CCU
7. 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)
8. Patients on lithium.
9. Patient in shock for another cause or moribund (SAPS2> 90).
10. Specific cardiogenic shock context: a. cardiac transplant patient or on transplant list. b. of peripartum, adrenergic, non ischemic valvular, post embolic heart disease. c. related to cardiotropic drug intoxication. d. secondary to a cardiocirculatory arrest for which the patient remains comatose before inclusion..

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hierarchical composite endpoint, assessed at 12 weeks from randomization (win-ratio method): - Rank 1: time to all-cause death or heart transplant or mechanical ventricular assist. - Rank 2: time to rehospitalization for heart failure - Rank 3: left ventricular ejection fraction assessed by echocardiography

Secondary endpoints 9

1. Death at 12 weeks
2. Heart transplantation or long-term ventricular assistance at 12 weeks
3. Rehospitalization for heart failure from hospital discharge to 12-week
4. Left ventricular ejection fraction at 12 weeks
5. Left ventricular relaxation and filling pressures assessed at 12 weeks: e' wave, E/e' ratio,
6. Right ventricular function assessed at 12 weeks: TAPSE, S wave
7. Number of patients requiring extra-renal purification between randomization and 12 weeks, and evolution of renal function assessed at randomization and at 12 weeks: glomerular filtration rate calculated by the CKD-EPI method
8. Liver function assessed at randomization and at 12 weeks: Bilirubin, Prothrombin Ratio , SGOT, SGPT.
9. Weight and NT-proBNP (at randomization and at 12 weeks).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

Sponsor organisation

CHRU De Nancy

Address

Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034

City

Nancy Cedex

Postcode

54035

Country

France

Scientific contact point

Organisation

CHRU De Nancy

Contact name

Antoine KIMMOUN

Public contact point

Organisation

CHRU De Nancy

Contact name

Antoine KIMMOUN

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications