Evaluation of Early Empagliflozin Administration on Mortality and Cardiac Function in Cardiogenic Shock: A Randomized Multicenter Trial

Trial ID: 2023-503602-37-00
Protocol: 2021PI218
Sponsor: CHRU De Nancy

Trial statistics

science

test molecule

location_city

research sites

public

country

medical_information

disease

person_search

investigators

Diseases & Conditions

Cardiogenic shock

Objectives

The primary objective of this study is to evaluate 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. This endpoint includes all-cause death, transplantation, long-term mechanical assistance, rehospitalization for heart failure, and left ventricular ejection fraction in patients with **cardiogenic shock**. This is clinically relevant as it aims to determine whether early intervention with empagliflozin can improve critical outcomes in this high-risk patient population.

Secondary objectives include:

Comparing the effect on all-cause mortality.
Assessing the impact on the number of heart transplants or long-term ventricular assistance.
Evaluating the number of rehospitalizations for heart failure.
Measuring changes in left ventricular ejection fraction.
Investigating left ventricular diastolic function and filling pressures at 12 weeks.
Examining right ventricular function at 12 weeks.
Assessing renal function at 12 weeks.
Evaluating hepatic function at 12 weeks.
Monitoring the evolution of hydro-sodic overload at 12 weeks.

These secondary objectives aim to provide a comprehensive understanding of the potential benefits of empagliflozin in various physiological parameters and clinical outcomes.

Participants

The clinical trial focuses on patients experiencing **cardiogenic shock**. The study population includes both male and female adults aged 18 years and older, who are hospitalized in critical cardiac care units or intensive care units. Participants are required to have been on catecholamine treatment for more than 12 hours. The trial involves a vulnerable population, as it includes individuals in critical health conditions. The sponsor has not provided information regarding the total number of participants. Participants must be affiliated with a social security scheme. The selection criteria ensure that the study population is representative of those typically affected by the condition under investigation.

Plans and Procedures

The clinical trial is designed to evaluate the effect of early initiation of **empagliflozin** in patients with **cardiogenic shock**. This is a randomized, multicentric, open trial with an estimated duration from May 2024 to August 2026. The trial aims to compare the outcomes of early empagliflozin introduction alongside usual management versus usual management alone over a period of 12 weeks. The primary endpoint is a hierarchical composite morbidity endpoint, assessed using the win-ratio method, which includes all-cause death, heart transplant, mechanical ventricular assist, rehospitalization for heart failure, and left ventricular ejection fraction. Secondary endpoints include death, heart transplantation, rehospitalization, and various cardiac and renal function assessments at 12 weeks.

Participants will be adult patients aged 18 years or older, hospitalized in critical cardiac care or intensive care units for cardiogenic shock, and on catecholamine for more than 12 hours. The trial will exclude any conditions not specified in the source data. The study involves several visits, starting with a screening visit to confirm eligibility based on the inclusion criteria. Follow-up visits will occur at regular intervals to monitor the participants' health status, medication adherence, and any adverse events. The end-of-study visit will take place at the 12-week mark to assess the primary and secondary endpoints.

The expected length of participant involvement is approximately 13 weeks, aligning with the maximum treatment period of the study drug, Jardiance 10 mg film-coated tablets, administered orally. Participants may be terminated early from the study if they experience significant adverse effects, withdraw consent, or if the investigator deems it necessary for their safety. The trial is not classified as low intervention and is conducted as a phase III trial to establish the efficacy of empagliflozin in this specific patient population. The study is conducted under the authorization of the relevant regulatory bodies, ensuring adherence to ethical and scientific standards.

Treatment

The clinical trial involves the administration of **Jardiance 10 mg film-coated tablets**, which contain the active substance **empagliflozin**. Empagliflozin is a **sodium glucose cotransporter 2 (SGLT2) inhibitor**, classified under the ATC code A10BK03. The pharmaceutical form of the medication is a film-coated tablet, designed for **oral use**. The dosage regimen for the trial specifies a maximum daily dose of 10 mg, with the treatment period extending up to 13 weeks. The medication is produced by Boehringer Ingelheim International GmbH and is not a pediatric formulation. The chemical origin of the active substance ensures its suitability for the intended therapeutic use in the study.

In addition to the experimental treatment with empagliflozin, participants will receive standard-of-care therapy as part of the usual management for their condition. This non-experimental treatment serves as a comparator to evaluate the efficacy of early empagliflozin initiation. The trial aims to assess the impact of empagliflozin on a composite morbidity endpoint, including all-cause death, transplantation, long-term mechanical assistance, rehospitalization for heart failure, and left ventricular ejection fraction. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy

Efficacy in the clinical trial titled "Effect at 3 months of early empagliflozin initiation in cardiogenic shock patients on mortality, rehospitalization, left ventricular ejection fraction and renal function" will be assessed using a hierarchical composite morbidity endpoint. This primary endpoint will be evaluated at 12 weeks from randomization using the win-ratio method. The hierarchical composite endpoint includes three ranks: Rank 1 assesses the time to all-cause death, heart transplant, or mechanical ventricular assist; Rank 2 evaluates the time to rehospitalization for heart failure; and Rank 3 measures the left ventricular ejection fraction, which will be assessed by echocardiography.

Secondary endpoints will also be evaluated at 12 weeks and include death, heart transplantation or long-term ventricular assistance, rehospitalization for heart failure, and left ventricular ejection fraction. Additional assessments will include left ventricular relaxation and filling pressures, right ventricular function, the number of patients requiring extra-renal purification, and the evolution of renal function, which will be assessed using the glomerular filtration rate calculated by the CKD-EPI method. Liver function will be evaluated through measurements of bilirubin, prothrombin ratio, SGOT, and SGPT. Weight and NT-proBNP levels will be measured at randomization and at 12 weeks.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Adult patients ≥18 years old hospitalized in critical cardiac unit care or Intensive care unit for a cardiogenic shock
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.
Person affiliated to a social security scheme

cancel

Exclusion Criteria

GFR< 20 ml/min/1.73m2.
Women of childbearing age without effective contraception
Type 1 diabete patient
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))
Chronic dialysis
Patient on SGLT2 inhibitors prior to admission to intensive care unit 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: 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..