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

Study Overview

• Status: Active, not recruiting
• Conditions: Fever; Blood Pressure; Acute Kidney Failure; Temperature; Cardiac Arrest (CA); Out of Hospital Cardiac Arrest; Sedation in Intensive Care Unit Patients; Mean Arterial Pressure Targets; Sedation in the ICU; Resuscitated Sudden Cardiac Death; Renal Replacement Therapy for Acute Kidney Injury in ICU; Sedation in Intensive Care
• Intervention / Treatment: Other: Deep sedation; Other: Fever control without a device; Device: Feedback-controlled temperature device; Other: High MAP; Other: Low MAP; Other: Minimal sedation

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.

• Study Type: Interventional
• Enrollment (Estimated): 3500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Princess Alexandra Hospital
  • Brisbane, Australia
    • The Prince Charles Hospital
  • Kingswood, Australia
    • Nepean Hospital
  • Liverpool, Australia
    • Liverpool Hospital
  • Melbourne, Australia
    • Austin Hospital
  • Sydney, Australia
    • Royal North Shore Hospital
  • Sydney, Australia
    • St George Hospital
  • Sydney, Australia
    • The Sutherland Hospital
• Belgium
  • Brussels, Belgium
    • HUB Hôpital Erasme
  • Ghent, Belgium
    • Ghent University Hospital
  • Lanaken, Belgium
    • Ziekenhuis Oost-Limburg Hospital
• Estonia
  • Tallinn, Estonia
    • North Estonia Medical Centre
• Finland
  • Espoo, Finland
    • Jorvi Hospital
  • Helsinki, Finland, 00290
    • Meilahti Hospital
  • Jyväskylä, Finland
    • Jyväskylä Hospital
  • Kuopio, Finland
    • Kuopio University Hospital
  • Oulu, Finland
    • Oulu University Hospital
• Germany
  • Berlin, Germany
    • Charite University Hospital
  • Lübeck, Germany
    • Lübeck University Hospital
  • Tübingen, Germany
    • Tubingen University Hospital
• Italy
  • Genova, Italy
    • San Martino Hospital Genova
• Luxembourg
  • Luxembourg, Luxembourg
    • Centre Hospitalier de Luxembourg
• New Zealand
  • Auckland, New Zealand
    • DCCM ICU
  • Auckland, New Zealand
    • Middlemore ICU
  • Auckland, New Zealand
    • North Shore ICU NZ
  • Christchurch, New Zealand
    • Christchurch Hospital
  • Wellington, New Zealand
    • Wellington Hospital
• Norway
  • Arendal, Norway
    • Soerlandet Hospital Arendal
  • Grålum, Norway
    • Kalnes Hospital
  • Oslo, Norway
    • Oslo University Hospital
  • Stavanger, Norway
    • Stavanger University Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Abdulaziz Medical City
• Singapore
  • Singapore, Singapore
    • Tan Tock Seng Hospital
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital
  • Halmstad, Sweden
    • Hallands hospital
  • Helsingborg, Sweden
    • Helsingborg Hospital
  • Karlstad, Sweden
    • Karlstad hospital
  • Lund, Sweden
    • Skåne University Hospital
  • Malmö, Sweden
    • Skåne University Hospital Malmö
  • Skövde, Sweden
    • Skaraborg Hospital Skovde
  • Stockholm, Sweden
    • Karolinska University Hospital
  • Umeå, Sweden
    • University Hospital of Umeå
• Switzerland
  • Bern, Switzerland
    • Bern University Hospital
  • Sankt Gallen, Switzerland
    • St Gallen Hospital
  • Zurich, Switzerland
    • University Hospital Zurich
• United Kingdom
  • Basildon, United Kingdom
    • Essex Cardiothoracic Centre
  • Bristol, United Kingdom
    • Bristol Royal Infirmary
  • Cardiff, United Kingdom
    • Cardiff University Hospital
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • London, United Kingdom
    • St Bartholomew's Hospital
  • London, United Kingdom
    • St Georges University Hospital
  • London, United Kingdom
    • Kings College Hospita

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sedation, temperature device and high MAP; Continuous deep sedation for 36 hours, fever management with a feedback-controlled device if temperature rises above 37.7°C and a mean arterial pressure target of ≥85mmHg	Other: Deep sedation; Deep sedation for at least 36h; Device: Feedback-controlled temperature device; If core body temperature exceeds 37.7°C a feedback-controlled device will be used and set at 37.5°C; Other: High MAP; A MAP target of >85mmHg will be used. Vasopressors will be titrated to this target during 36h
Active Comparator: Sedation, no temperature device and high MAP; Continuous deep sedation for 36 hours, fever management without a feedback-controlled device and a mean arterial pressure target of ≥85mmHg	Other: Deep sedation; Deep sedation for at least 36h; Other: Fever control without a device; Management of fever in the ICU without a device; Other: High MAP; A MAP target of >85mmHg will be used. Vasopressors will be titrated to this target during 36h
Active Comparator: Sedation, temperature device and low MAP; Continuous deep sedation for 36 hours, fever management with a feedback-controlled device if temperature rises above 37.7°C and a mean arterial pressure target of ≥65mmHg	Other: Deep sedation; Deep sedation for at least 36h; Device: Feedback-controlled temperature device; If core body temperature exceeds 37.7°C a feedback-controlled device will be used and set at 37.5°C; Other: Low MAP; A MAP target of >65mmHg will be used. Vasopressors will be titrated to this target during 36h
Active Comparator: Sedation, no temperature device and low MAP; Continuous deep sedation for 36 hours, fever management without a feedback-controlled device and a mean arterial pressure target of ≥65mmHg	Other: Deep sedation; Deep sedation for at least 36h; Other: Fever control without a device; Management of fever in the ICU without a device; Other: Low MAP; A MAP target of >65mmHg will be used. Vasopressors will be titrated to this target during 36h
Active Comparator: Minimal sedation, temperature device and high MAP; Minimal sedation (and early extubation if possible), fever management with a feedback-controlled device if temperature rises above 37.7°C and a mean arterial pressure target of ≥85mmHg	Device: Feedback-controlled temperature device; If core body temperature exceeds 37.7°C a feedback-controlled device will be used and set at 37.5°C; Other: High MAP; A MAP target of >85mmHg will be used. Vasopressors will be titrated to this target during 36h; Other: Minimal sedation; A strategy of minimal sedation in the ICU, sedation used only as needed to facilitate transport, imaging and invasive procedures
Active Comparator: Minimal sedation, no temperature device and high MAP; Minimal sedation (and early extubation if possible), fever management without a feedback-controlled device and a mean arterial pressure target of ≥65mmHg	Other: Fever control without a device; Management of fever in the ICU without a device; Other: High MAP; A MAP target of >85mmHg will be used. Vasopressors will be titrated to this target during 36h; Other: Minimal sedation; A strategy of minimal sedation in the ICU, sedation used only as needed to facilitate transport, imaging and invasive procedures
Active Comparator: Minimal sedation, temperature device and low MAP; Minimal sedation (and early extubation if possible), fever management with a feedback-controlled device if temperature rises above 37.7°C and a mean arterial pressure target of ≥65mmHg	Device: Feedback-controlled temperature device; If core body temperature exceeds 37.7°C a feedback-controlled device will be used and set at 37.5°C; Other: Low MAP; A MAP target of >65mmHg will be used. Vasopressors will be titrated to this target during 36h; Other: Minimal sedation; A strategy of minimal sedation in the ICU, sedation used only as needed to facilitate transport, imaging and invasive procedures
Active Comparator: Minimal sedation, no temperature device and low MAP; Minimal sedation (and early extubation if possible), fever management without a feedback-controlled device and a mean arterial pressure target of ≥65mmHg	Other: Fever control without a device; Management of fever in the ICU without a device; Other: Low MAP; A MAP target of >65mmHg will be used. Vasopressors will be titrated to this target during 36h; Other: Minimal sedation; A strategy of minimal sedation in the ICU, sedation used only as needed to facilitate transport, imaging and invasive procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse kidney event (MAKE)	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	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between baseline and the highest in-hospital creatinine	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	During the stay in the index hospital following cardiac arrest, until discharge or transfer to another hospital, and within 30 days
Difference between baseline and the last measured in-hospital creatinine	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)	At the time of discharge or transfer to another hospital from the index hospital following cardiac arrest, and within 30 days
Difference between baseline and 72-hour creatinine	Difference between baseline (the highest outpatient creatinine in the previous six months, or if unavailable, the creatinine on admission) and 72-hour creatinine	72 hours
Difference between baseline and the highest creatinine within 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	72 hours

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Renal Insufficiency; Body Temperature Changes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Acute Kidney Injury; Heart Arrest; Fever; Out-of-Hospital Cardiac Arrest; Anesthesia and Analgesia; Deep Sedation
• Other Study ID Numbers: STEPCARE-MAKE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No