Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2)

Abstract

Background and Purpose Therapeutic hypothermia (TH) is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. TH for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster TH in stroke patients. Methods Safety procedures and 4°C saline infusions for faster cooling were added to the Intravascular Cooling Treatment in Acute Stroke (ICTuS) trial protocol. A femoral venous intravascular cooling catheter following intravenous rt-PA in eligible patients provided 24 hours cooling followed by a 12 hour re-warm. Serial safety assessments and imaging were performed. The primary endpoint was 3-month modified Rankin score 0,1. Results Of the intended 1600 subjects, 120 were enrolled before the study was stopped. Randomly, 63 were to receive hypothermia (HY) plus anti-shivering treatment and 57 normothermia (NT). Compared to prior studies, cooling rates were improved with a cold saline bolus, without fluid overload. The intention-to-treat primary outcome of 90-day mRS 0,1 occurred in 33% HY and 38% NT subjects, OR (95% CL) of 0.81 (0.36, 1.85). Serious adverse events occurred equally. Mortality was 15.9% HY and 8.8% NT subjects, OR (95% CL) of 1.95 (0.56, 7.79). Pneumonia occurred in 19% HY vs. 10.5% in NT subjects, OR (95% CL) of 1.99 (0.63, 6.98). Conclusion Intravascular TH was confirmed to be safe and feasible in rt-PA treated acute ischemic stroke patients. Protocol changes designed to reduce pneumonia risk appeared to fail, although the sample is small. Clinical trial registration clinicaltrials.gov NCT 01123161.

Reconsidering Neuroprotection in the Reperfusion Era

“…42 Some studies in this setting include combination of neuroprotective approaches with intravenous thrombolysis. 43,44 The emergence of endovascular thrombectomy as the standard of care for LVO has led to the development of rapid transfer systems of care to obtain eligible patients to comprehensive stroke centers. There are 3 possible methods to triage LVO to endovascular centers: -Secondary transport (drip and ship): prehospital transport to the closest stroke center for earlier intravenous thrombolysis and in-hospital screening for LVO followed by secondary ambulance/helicopter transport to an endovascular center.…”

Therapeutic hypothermia and acute brain injury

“…The effect of cooling on thrombolysis (rtPA) is negligible. 8 The therapeutic hypothermia for acute ischaemia stroke (EuroHYP-1), was supposed to be the largest (1500 patients), pan-European phase III RCT. The primary endpoint was functional outcomes at three months in conscious stroke patients.…”

Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke

“…The more recent ICTuS follow-up evaluated 120 subjects randomly assigned to hypothermia versus normothermia before the study was terminated. 96 Several large meta-analyses evaluating hypothermia during brain surgery 44 and cardiac surgery 11 have been published. Whereas results for improved neurological function after brain surgery were nonsignificant, mild therapeutic hypothermia was concluded to improve neurological outcome after cardiac arrest but not during in-hospital cardiac arrest, asystole, or noncardiac causes of arrest.…”