Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2)
Authors: Lyden Patrick , Hemmen Thomas , Grotta James , Rapp Karen , Ernstrom Karin , Rzesiewicz Teresa , Parker Stephanie , Concha Mauricio , Hussain Syed , Agarwal Sachin , Meyer Brett , Jurf Julie , Altafullah Irfan , Raman Rema ,   Collaborators, Hess Mary Jane , Mullin Anthony , Jane Hess Mary , Muranevici Gabriela , Piantadosi Bonnie , Jimenez-Maggiora Gustavo , So Jia-Shing , Jain Sonia , Diringer Michael , Derdeyn Colin , Stern Barney , Hamilton Scott , Dietrich Dalton , Becker Kyra , Yenari Midori , Dirnagl Ulrich , Wijman Christine , Chamorro Ángel , Janis Scott , Moy Claudia , Lin Felice , Song Shlee , Schlick Konrad , Khanolkar Pooja , Edwards Nancy J. , Roldan Ana , Wilson Jeanette , Little Amy , Lewis Pam , Neil William , Bruce Nhu , Guzik Amy , Sohdi Ajeet , Herial Nabeel , Ovbiagele Bruce , Meyer Dawn , Modir Royya , Chavez Ronelyn , Velazquez Angela , Mayer Stephan , Claassen Jan , Falo Cristina , Tafreshi Gilda , Neil William , Bruce Nhu , Guzik Amy , Modir Royya , Kelly Nancy , Chavez Ronelyn , Ovbiagele Bruce , Shell Erin , Dugan Guy , Kim Elizabeth , Tanner Amy , Michel Patrik , Eskandari Ashraf , Oddo Mauro , Suys Tamarah , Remillard Suzette , Cordier Maria , Brown Robert , Jasak Sara , McCullough Louise , Brautigam Robert , Alexandrov Andrei , Sisson April , Albright Karen , Broessner Gregor , Schmutzhard Erich , Escioglou Elissanet , Jones William , Poisson Sharon , Simpson Jennifer , Shah Qaisar , Jonczak Karin , Bussinger Patricia , Lewandowski Christopher , Berry Shannen , Lundell AnneMarie , Miller Joseph B. , Cruz-Flores Salvador , Holzer Eve , Torretta Susan , Brown David , Heim Laura , Smith Carlos , Kelley Chip , Greer David , Marcolini Evadne G. , Gilmore Emily J. , Rutledge Neil , McBee Del , Khanna Anna , Warren Sonisha , Wilsom Christina , Shushrutha Hedna Vishnumurthy , Rosado Christian , Kizza Rosie , O’Phelan Kristine , Escobar Andrea , Merenda Amedeo , Perez Barcena Juan , Malik Amer 
Published: November 2016

Background and Purpose—

Therapeutic hypothermia is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. Therapeutic hypothermia for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster therapeutic hypothermia in stroke patients.

Methods—

Safety procedures and 4°C saline infusions for faster cooling were added to the ICTuS trial (Intravascular Cooling in the Treatment of Stroke) protocol. A femoral venous intravascular cooling catheter after intravenous recombinant tissue-type plasminogen activator in eligible patients provided 24 hours cooling followed by a 12-hour rewarm. Serial safety assessments and imaging were performed. The primary end point 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 plus antishivering treatment and 57 normothermia. Compared with previous studies, cooling rates were improved with a cold saline bolus, without fluid overload. The intention-to-treat primary outcome of 90-day modified Rankin Score 0,1 occurred in 33% hypothermia and 38% normothermia subjects, odds ratio (95% confidence interval) of 0.81 (0.36–1.85). Serious adverse events occurred equally. Mortality was 15.9% hypothermia and 8.8% normothermia subjects, odds ratio (95% confidence interval) of 1.95 (0.56–7.79). Pneumonia occurred in 19% hypothermia versus 10.5% in normothermia subjects, odds ratio (95% confidence interval) of 1.99 (0.63–6.98).

Conclusions—

Intravascular therapeutic hypothermia was confirmed to be safe and feasible in recombinant tissue-type plasminogen activator–treated acute ischemic stroke patients. Protocol changes designed to reduce pneumonia risk appeared to fail, although the sample is small.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01123161.