Effects of Sedation, TEmperature and Pressure After Cardiac Arrest and REsuscitation on Major Adverse Kidney Events (STEPCARE-MAKE)

Effects of Sedation, TEmperature and Pressure After Cardiac Arrest and REsuscitation on Major Adverse Kidney Events (STEPCARE-MAKE): a Protocol for a Pre-planned Sub-study of a Randomized Clinical Trial

The STEPCARE-MAKE study is a predefined sub-study of the large Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial, which evaluates the effects of three interventions in comatose adult patients resuscitated from out-of-hospital cardiac arrest. In this sub-study, all 3500 participants enrolled in the main trial are assessed for major adverse kidney events (MAKE) and creatinine kinetics.

The main STEPCARE trial randomizes patients to three different interventions: (1) continuous deep sedation for 36 hours or minimal sedation (with extubation if feasible), (2) fever control with or without a feedback-controlled device if the temperature rises above 37.7°C, and (3) a mean arterial pressure (MAP) target of ≥65 mmHg or ≥85 mmHg.

This sub-study evaluates the effects of these three interventions on major adverse kidney events (MAKE), defined as a composite of death within 30 days, initiation of renal replacement therapy during the stay in the primary hospital, or persistent renal dysfunction, defined as a final creatinine value ≥200% of baseline at the time of discharge from the primary hospital.

Creatinine kinetics during the stay in the primary hospital and within 72 hours post-resuscitation are evaluated as secondary outcomes.

All data are collected prospectively as part of the main trial protocol, and analyses will be conducted according to a predefined statistical analysis plan.

Inclusion Criteria:

• All patients included to the main STEPCARE-trial are also included to this substudy
• Out-of-hospital cardiac arrest
• Sustained return of spontaneous circulation, defined as 20 minutes with signs of circulation without the need for chest compressions
• Unconsciousness (FOUR-score motor response <4, inability to obey verbal commands), or being intubated and sedated due to agitation
• Eligible for intensive care without restrictions or limitations
• Inclusion within 4 hours of the return of spontaneous circulation

Exclusion Criteria:

• Out-of-hospital cardiac arrest of presumed traumatic or hemorrhagic origin
• Confirmed or suspected intracranial hemorrhage
• Pregnancy
• Extracorporeal membrane oxygenation (ECMO) prior to randomization
• No additional exclusion criteria are applied beyond those of the main STEPCARE trial