Acute Kidney Failure, Blood Pressure, Cardiac Arrest (CA), Fever, Mean Arterial Pressure Targets, Out of Hospital Cardiac Arrest, Renal Replacement Therapy for Acute Kidney Injury in ICU, Resuscitated Sudden Cardiac Death, Sedation in Intensive Care, Sedation in Intensive Care Unit Patients, Sedation in the ICU, Temperature
Conditions
Brief summary
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.
Detailed description
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.
Interventions
If core body temperature exceeds 37.7°C a feedback-controlled device will be used and set at 37.5°C
OTHERHigh MAP
A MAP target of \>85mmHg will be used. Vasopressors will be titrated to this target during 36h
OTHERDeep sedation
Deep sedation for at least 36h
Management of fever in the ICU without a device
OTHERLow MAP
A MAP target of \>65mmHg will be used. Vasopressors will be titrated to this target during 36h
OTHERMinimal sedation
A strategy of minimal sedation in the ICU, sedation used only as needed to facilitate transport, imaging and invasive procedures
Sponsors
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants will be blinded. Assessors of neurological prognosis will be blinded. Outcome assessors and investigators will be blinded. Health-care personnel will not be blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse kidney event (MAKE) | 30 days | A composite endpoint of MAKE: death from any cause by day 30, initiation of RRT during the stay in the primary hospital or persistent renal dysfunction defined as final creatinine value ≥200 % of the baseline (the highest outpatient creatinine in the previous six months, or if unavailable, the creatinine on admission) at the time of discharge from the primary hospital |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference between baseline and the highest in-hospital creatinine | During the stay in the index hospital following cardiac arrest, until discharge or transfer to another hospital, and within 30 days | Difference between baseline (the highest outpatient creatinine in the previous six months, or if unavailable, the creatinine on admission) and the highest in-hospital creatinine |
| Difference between baseline and the last measured in-hospital creatinine | At the time of discharge or transfer to another hospital from the index hospital following cardiac arrest, and within 30 days | Difference between baseline (the highest outpatient creatinine in the previous six months, or if unavailable, the creatinine on admission) and the last measured in-hospital creatinine (in the primary hospital) |
| Difference between baseline and 72-hour creatinine | 72 hours | Difference between baseline (the highest outpatient creatinine in the previous six months, or if unavailable, the creatinine on admission) and 72-hour creatinine |
| Difference between baseline and the highest creatinine within 72 hours | 72 hours | Difference between baseline (the highest outpatient creatinine in the previous six months, or if unavailable, the creatinine on admission) and the highest creatinine within 72 hours |
Countries
Australia, Belgium, Estonia, Finland, Germany, Italy, Luxembourg, New Zealand, Norway, Saudi Arabia, Singapore, Sweden, Switzerland, United Kingdom
Outcome results
None listed