Levosimendan in Cardiac Arrest (LeiCA): Protocol for a Randomized, Double-Blind, Phase II Clinical Trial

Abstract

Background: Despite developments in advanced life support, outcomes after out-of-hospital cardiac arrest (OHCA) remain poor. Levosimendan, a calcium-sensitizing inodilator commonly used in heart failure, has shown beneficial effects in several experimental models and anecdotal clinical cases of cardiac arrest. The Levosimendan in Cardiac Arrest (LeiCA) pilot trial will evaluate levosimendan as an adjunct to advanced life support in refractory OHCA.

Methods: This will be an investigator-initiated, randomized, double-blind, placebo-controlled, single-center pilot trial. Patients aged 18-75 years with witnessed, nontraumatic, refractory OHCA in Stockholm County, Sweden, will be eligible for enrollment by a physician-staffed emergency medical service unit. Forty patients will be randomized in a 3:1 ratio to receive a single intravenous bolus of either levosimendan 2.5 mg (n = 30) or placebo (n = 10), administered during cardiopulmonary resuscitation via prefilled, masked syringes. Both groups will receive routine advanced life support and postresuscitation care as applicable. Included patients eligible for hospital transfer will be admitted to Karolinska University Hospital in Solna, Stockholm, Sweden. The primary endpoint is 30-day survival. Secondary endpoints include additional clinical outcome measures.

Conclusion: The LeiCA pilot trial will investigate the effects of levosimendan as an adjunct to advanced life support for refractory OHCA. The results will inform the design of a definitive multicenter trial.

Trial registration: ISRCTN15862521; October 22, 2025.