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

Patrick Lyden; Thomas Hemmen; James Grotta; Karen Rapp; Karin Ernstrom; Teresa Rzesiewicz; Stephanie Parker; Mauricio Concha; Syed Hussain; Sachin Agarwal; Brett Meyer; Julie Jurf; Irfan Altafullah; Rema Raman; Collaborators

doi:10.1161/STROKEAHA.116.014200

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

Stroke. 2016 Dec;47(12):2888-2895. doi: 10.1161/STROKEAHA.116.014200. Epub 2016 Nov 10.

Collaborators

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

Affiliations

¹ From the Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA (P.L.); Department of Neurosciences (T.H., K.R., B.M.) and Sanford Stem Cell Clinical Center (T.R.), University of California, San Diego; Department of Neurology, Memorial Health Care System, Houston, TX (J.G.); Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego (K.E., R.R.); Department of Neurology, University of Texas McGovern Medical School, Houston (S.P.); Department of Neurosciences, Sarasota Memorial Health Care System, FL (M.C.); Department of Neurology, Michigan State University, Kalamazoo (S.H.); Department of Neurology, Columbia University, New York, NY (S.A.); Performance Improvement Patient Safety Department, UC San Diego Health System, CA (J.J.); and Department of Neurology, North Memorial Medical Center, Minneapolis, MN (I.A.). lydenp@cshs.org.
² From the Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA (P.L.); Department of Neurosciences (T.H., K.R., B.M.) and Sanford Stem Cell Clinical Center (T.R.), University of California, San Diego; Department of Neurology, Memorial Health Care System, Houston, TX (J.G.); Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego (K.E., R.R.); Department of Neurology, University of Texas McGovern Medical School, Houston (S.P.); Department of Neurosciences, Sarasota Memorial Health Care System, FL (M.C.); Department of Neurology, Michigan State University, Kalamazoo (S.H.); Department of Neurology, Columbia University, New York, NY (S.A.); Performance Improvement Patient Safety Department, UC San Diego Health System, CA (J.J.); and Department of Neurology, North Memorial Medical Center, Minneapolis, MN (I.A.).

Abstract

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.

Keywords: hypothermia; intention to treat analysis; ischemic stroke; neuroprotection; pneumonia; stroke; therapeutics.

Publication types

Multicenter Study
Randomized Controlled Trial

MeSH terms

Aged
Aged, 80 and over
Female
Follow-Up Studies
Humans
Hypothermia, Induced / adverse effects
Hypothermia, Induced / instrumentation
Hypothermia, Induced / methods*
Hypothermia, Induced / standards
Male
Middle Aged
Outcome Assessment, Health Care*
Single-Blind Method
Stroke / therapy*

Associated data

ClinicalTrials.gov/NCT01123161

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

Authors

Collaborators

Affiliations

Abstract

Publication types

MeSH terms

Associated data

Grants and funding