Table 4: Randomized controlled trials assessing neurologic outcomes after cardiac arrest—ongoing trials.

Trial nameStudy
Control groupTarget enrollmentOutcome measurePIComments

Neuroprotective drugs

Selenium to Improve Neurological Outcome after Cardiac Arrest (SCPR)Randomized, double-blind, placebo-controlled, single-center, phase 2a efficacy studySodium-selenite infusion × 7 daysPlacebo52Primary outcome: neuron-specific enolase
Secondary outcomes: inflammation and oxidative stress markers, NIHSS and Glasgow Pittsburgh performance score at 6 months, selenium blood levels, glutathione peroxidase plasma levels
Vanessa Stadlbauer and Karlheinz Smolle,
Selenium can reduce oxidative stress after cardiac arrest and reduce inflammation


Clinical Study of the LRS ThermoSuit System in Post Arrest Patients with Intravenous Infusion of Magnesium SulfateRandomized, double-blind, parallel assignment, safety/efficacy study of any rhythmThermosuit to target 34°C plus magnesium sulfate IV (30 mg/kg over 15 minutes)ThermoSuit to target 34°C plus placebo (normal saline)14Primary outcome: cooling rate
Secondary outcomes: time to target temperature, percentage of time in target temperature range, shivering, length of stay, neurologic status at discharge and 6 months, adverse events, survival at 24 hours, discharge and 30 days
Michael Holzer and Andreas Janata, NCT00593164Tests new device to achieve therapeutic hypothermia and the impact of magnesium on cooling performance and hemodynamics


Target Temperature Management after Cardiac Arrest (TTM)Randomized, double-blind, parallel assignment, multicenter, safety/efficacy trial for out-of-hospital cardiac arrestTarget temperature 36°C × 24 hTarget temperature 33°C × 24 h850Primary outcome: All cause mortality
Secondary outcomes: 6-month composite all cause mortality and poor neurological outcome by cerebral performance scale, bleeding, 6-month neurological status and quality of life, mRS, Cerebral performance scale, mini-mental test, IQCODE, SF-36, adverse events
Niklas Nielsen and Hans, Friberg NCT01020916Attempts to identify optimal hypothermia target temperature
Hypothermia After in-Hospital Cardiac Arrest (HACAinhospital)Randomized, single-blind, parallel assignment, single-center, safety/efficacy study for in-hospital arrests of any rhythmMild therapeutic hypothermia 32–34°C × 24 hours.Standard care, no hypothermia440Primary outcome: all cause mortality at 6 months
Secondary outcomes: 6 month Glasgow-Pittsburgh cerebral performance scale, in-hospital all-cause mortality
Sebastian Wolfrum and Volkhard Kurowski,
Tests whether hypothermia treatment will improve outcome after in-hospital arrest of any rhythm
Intra-arrest Therapeutic Hypothermia in Prehospital Cardiac Arrest (HITUPPAC-BIO)Randomized, open label, parallel assignment, efficacy trialHypothermia induction prehospitalHypothermia induction at hospital arrival250Primary outcomes: brain injury biomarkers at 72 h
Secondary outcomes: ROSC, survival 72 h, GCS at 48 hours, cerebral performance scale at 28 days
Guillaume Debaty Jean Francois Timsit, NCT00886184Assess utility of early hypothermia prehospital
Induction of Mild Hypothermia Following Out-of-hospital Cardiac Arrest Randomized, open label, single group assignment, efficacy study of any rhythm out of hospital arrestRapid infusion of 2 L of 4°C normal saline prior to ED arrivalStandard therapy1364Primary outcome: awake and command following at hospital discharge
Secondary outcomes: days to awakening, days to death, 3 month neurological outcome
Francis Kim,
Tests whether rapid induction of hypothermia with cold saline infusion is efficacious
Comparing Therapeutic Hypothermia Using External and Internal Cooling for Post-Cardiac Arrest PatientsRandomized, open label, parallel assignment, efficacy trialExternal device (Arctic Sun) induced hypothermiaInternal device (Alsius) induced hypothermia51Primary outcome: Survival to hospital discharge
Secondary outcome: 1 year neurological status
Marcus Ong, NCT00827957Identifying the most efficient method of cooling may improve outcome after cardiac arrest

Hypothermia + ECMO

Refractory Out-of-Hospital Cardiac Arrest Treated with Mechanical CPR, Hypothermia, ECMO and Early Reperfusion (CHEER)Nonrandomized, single group, open label, safety/efficacy trail for patients who fail standard resuscitationAutomated CPR, ECMO, coronary angiography, therapeutic hypothermiaNA24Primary outcome: survival to hospital discharge
Secondary outcomes: cerebral performance Scale, time to ECMO insertion, neurologic biomarkers, cardiac recovery
Stephen Bernard and Dion Stub, NCT01186614Aggressive resuscitation may improve outcome in patients who fail standard resuscitation
Hyperinvasive approach to out-of-hospital cardiac arrest using mechanical chest compression device, prehospital intraarrest cooling, extracorporeal Life support and early Invasive assessment compared to standard of care: Prague OHCA StudyRandomized, open-label, parallel group, safety/efficacy studyPrehospital mechanical compression device, intraarrest cooling and in hospital ECLS (compression device, Rhinochill, PLS ECMO)Standard care170Primary outcome: composite endpoint of survival with good neurological outcome (cerebral performance scale)
Secondary outcome: 30 day cerebral performance scale, 30 day cardiac recovery
Jan Belohlavek and Ondrej Smid,
Aggressive, early intervention may improve cerebral outcomes
Emergency Preservation and Resuscitation (EPR) for Cardiac Arrest from Trauma (EPR-CAT)Nonrandomized, open label, parallel assignment, safety/efficacy studyProfound hypothermia < 10°C with cold saline infusion into aorta followed by resuscitation/rewarming with cardiopulmonary bypassStandard treatment20Primary outcome: survival to hospital discharge without major disability by GOSE
Secondary outcomes: achieving target temperature in 1 hour, 28 day survival, 6 month neurological function, multiple organ system dysfunction
Samuel Tisherman,
Resuscitation technique for trauma patients that have arrested from exsanguination

HypotherMia + xenon

Effect of xenon and therapeutic hypothemia on brain and on neuroloigcal outcome following brain ischemia in cardiac arrest patients (Xe-hypotheca)Randomzied, open label, parallel assignment, phase 2 safety/efficacy trial for ventricular fibrillation and nonperfusing ventricular tachycardiaHypothermia 33°C × 24 h and Xenon inhalation × 24 hours target end tidal 40%Hypothermia 33°C × 24 h110Primary outcome: PET and MRI ischemia at 24 hours and 10 days
Secondary outcomes: neurological outcome at 6 months, TTE
Timo Laitio,
Xenon may be synergistically neuroprotective in combination with hypothermia post arrest by limiting cerebral hypoxia, neuronal loss, and mitochondrial dysfunction

Chest compresions

Continuous chest compressionsRandomized, open label, multicenter, crossover assignment study of out-of-hospital cardiac arrest of any rhythmContinuous chest compressionsInterrupted chest compressions with ventilation 30 : 223600Primary outcome: survival to hospital discharge
Secondary outcomes: mRS at discharge, adverse events
Myron Weisfeldt,
Continuous CPR without interruption for ventilation may be superior to interrupted compression with ventilation ratio of 30 : 2
LUCAS chest compressor versus manual chest compression in out-of-hospital sudden cardiac arrest: LUCAT trialRandomized, open label, parallel assignment, efficacy studyMechanical continuous chest compressions performed by LUCAS deviceManual chest compressions400Primary outcome: survival to hospital admission, survival to discharge with good neurological state by cerebral performance Scale
Secondary outcomes: ROSC, end tidal CO2, SOFA scale, length of stay, metabolic and inflammatory markers, LV function
Francesc Carmona Jimenez, Rosa-Maria Lidon,
Mechanical chest compression may be superior to manual chest compression

Cerebral oxygenation

Cerebral Oxygenation in Cardiac Arrest and HypothermiaOpen label, safety and efficacy studyNear-infrared monitoringStandard therapy, no monitoring70Primary outcome: survival to discharge
Secondary outcomes: cerebral performance scale at discharge and 12 months
Christian Storm, NCT01531426Near-infrared spectroscopy (NIRS) could be a new-noninvasive marker for outcome after cardiac arrest. Low NIRS may correlate with poor outcome