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



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.



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).



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.



URL: http://www.clinicaltrials.gov. Unique identifier: NCT01123161.
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.
Patrick
P
Lyden
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.).
Thomas
T
Hemmen
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.).
James
J
Grotta
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.).
Karen
K
Rapp
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.).
Karin
K
Ernstrom
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.).
Teresa
T
Rzesiewicz
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.).
Stephanie
S
Parker
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.).
Mauricio
M
Concha
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.).
Syed
S
Hussain
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.).
Sachin
S
Agarwal
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.).
Brett
B
Meyer
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.).
Julie
J
Jurf
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.).
Irfan
I
Altafullah
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.).
Rema
R
Raman
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D016037:Single-Blind Method; D020521:Stroke / Q000628:therapy*
hypothermia; intention to treat analysis; ischemic stroke; neuroprotection; pneumonia; stroke; therapeutics