(CCSP069) INOTROPE VERSUS PLACEBO THERAPY IN CARDIOGENIC SHOCK: THE CAPITAL DOREMI2 TRIAL

Background: Cardiogenic shock (CS) is a state of low cardiac output associated with end-organ hypoperfusion, with mortality ranging upwards of 40%. Current guidelines support their use in the management of CS, although no convincing evidence of efficacy exists. Furthermore, inotropes are associated with harm in the heart failure population, including increased myocardial oxygen demand, tachyarrhythmias, hypotension, and longer ICU and in-hospital lengths of stay. Our research group completed the first randomized trial comparing two of these agents, milrinone and dobutamine, in a cohort of patients with CS and observed no difference in outcomes. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS.

METHODS AND RESULTS: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo, which will be administered over a 12-hour period (Figure 1). After this, participants will continue open-label therapies at the discretion of the treating team. The primary endpoint is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. Any participant that meets one or more components of the primary endpoint during the 12-hour period will stop the study drug at that time and receive open-label inotrope therapy at the discretion of the treating team. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge.

Enrollment began in March 2022, and we have randomized 102 participants to date. We expect a total of 6 sites across North America to commence enrollment by mid 2023, and expect to reach our target sample size by March 2025.

Conclusion: This trial will be the first to establish the safety and efficacy of single inotrope therapy against placebo in a population of patients with CS. The results will inform both clinical practice and evidence-based policy decisions, improving the care we provide to this vulnerable population.