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; Mary Jane Hess; Anthony Mullin; 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; Nancy Kelly; 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; Austin Seton; 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

doi:10.1161/STROKEAHA.116.014200

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, Mary Jane Hess, Anthony Mullin, Gabriela Muranevici, Bonnie Piantadosi, Gustavo Jimenez-Maggiora, Jia Shing SoSonia 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, Nancy Kelly, 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, Austin Seton, 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

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2888-2895
Number of pages	8
Journal	Stroke
Volume	47
Issue number	12
DOIs	https://doi.org/10.1161/STROKEAHA.116.014200
State	Published - Dec 1 2016
Externally published	Yes

Keywords

hypothermia
intention to treat analysis
ischemic stroke
neuroprotection
pneumonia
stroke
therapeutics

ASJC Scopus subject areas

Clinical Neurology
Cardiology and Cardiovascular Medicine
Advanced and Specialized Nursing

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10.1161/STROKEAHA.116.014200

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Lyden, P., Hemmen, T., Grotta, J., Rapp, K., Ernstrom, K., Rzesiewicz, T., Parker, S., Concha, M., Hussain, S., Agarwal, S., Meyer, B., Jurf, J., Altafullah, I., Raman, R., Hess, M. J., Mullin, A., Muranevici, G., Piantadosi, B., Jimenez-Maggiora, G., ... Malik, A. (2016). Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2). Stroke, 47(12), 2888-2895. https://doi.org/10.1161/STROKEAHA.116.014200

Lyden, P, Hemmen, T, Grotta, J, Rapp, K, Ernstrom, K, Rzesiewicz, T, Parker, S, Concha, M, Hussain, S, Agarwal, S, Meyer, B, Jurf, J, Altafullah, I, Raman, R, Hess, MJ, Mullin, A, Muranevici, G, Piantadosi, B, Jimenez-Maggiora, G, So, JS, Jain, S, Diringer, M, Derdeyn, C, Stern, B, Hamilton, S, Dietrich, D, Becker, K, Yenari, M, Dirnagl, U, Wijman, C, Chamorro, Á, Janis, S, Moy, C, Lin, F, Song, S, Schlick, K, Khanolkar, P, Edwards, NJ, Roldan, A, Wilson, J, Little, A, Lewis, P, Neil, W, Bruce, N, Guzik, A, Sohdi, A, Herial, N, Ovbiagele, B, Meyer, D, Modir, R, Chavez, R, Velazquez, A, Mayer, S, Claassen, J, Falo, C, Tafreshi, G, Kelly, N, Shell, E, Dugan, G, Kim, E, Tanner, A, Michel, P, Eskandari, A, Oddo, M, Suys, T, Remillard, S, Cordier, M, Brown, R, Jasak, S, McCullough, L, Brautigam, R, Alexandrov, A, Sisson, A, Albright, K, Broessner, G, Schmutzhard, E, Escioglou, E, Jones, W, Poisson, S, Simpson, J, Shah, Q, Jonczak, K, Bussinger, P, Lewandowski, C, Berry, S, Lundell, A, Miller, JB, Cruz-Flores, S, Holzer, E, Torretta, S, Brown, D, Heim, L, Smith, C, Kelley, C, Greer, D, Marcolini, EG, Gilmore, EJ, Seton, A, Rutledge, N, McBee, D, Khanna, A, Warren, S, Wilsom, C, Hedna, VS, Rosado, C, Kizza, R, O’phelan, K, Escobar, A, Merenda, A, Barcena, JP & Malik, A 2016, 'Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2)', Stroke, vol. 47, no. 12, pp. 2888-2895. https://doi.org/10.1161/STROKEAHA.116.014200

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title = "Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2)",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2016 American Heart Association, Inc.",

year = "2016",

month = dec,

day = "1",

doi = "10.1161/STROKEAHA.116.014200",

language = "English (US)",

volume = "47",

pages = "2888--2895",

journal = "Stroke",

issn = "0039-2499",

publisher = "Lippincott Williams and Wilkins",

number = "12",

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TY - JOUR

T1 - Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2)

AU - Lyden, Patrick

AU - Hemmen, Thomas

AU - Grotta, James

AU - Rapp, Karen

AU - Ernstrom, Karin

AU - Rzesiewicz, Teresa

AU - Parker, Stephanie

AU - Concha, Mauricio

AU - Hussain, Syed

AU - Agarwal, Sachin

AU - Meyer, Brett

AU - Jurf, Julie

AU - Altafullah, Irfan

AU - Raman, Rema

AU - Hess, Mary Jane

AU - Mullin, Anthony

AU - Muranevici, Gabriela

AU - Piantadosi, Bonnie

AU - Jimenez-Maggiora, Gustavo

AU - So, Jia Shing

AU - Jain, Sonia

AU - Diringer, Michael

AU - Derdeyn, Colin

AU - Stern, Barney

AU - Hamilton, Scott

AU - Dietrich, Dalton

AU - Becker, Kyra

AU - Yenari, Midori

AU - Dirnagl, Ulrich

AU - Wijman, Christine

AU - Chamorro, Ángel

AU - Janis, Scott

AU - Moy, Claudia

AU - Lin, Felice

AU - Song, Shlee

AU - Schlick, Konrad

AU - Khanolkar, Pooja

AU - Edwards, Nancy J.

AU - Roldan, Ana

AU - Wilson, Jeanette

AU - Little, Amy

AU - Lewis, Pam

AU - Neil, William

AU - Bruce, Nhu

AU - Guzik, Amy

AU - Sohdi, Ajeet

AU - Herial, Nabeel

AU - Ovbiagele, Bruce

AU - Meyer, Dawn

AU - Modir, Royya

AU - Chavez, Ronelyn

AU - Velazquez, Angela

AU - Mayer, Stephan

AU - Claassen, Jan

AU - Falo, Cristina

AU - Tafreshi, Gilda

AU - Kelly, Nancy

AU - Shell, Erin

AU - Dugan, Guy

AU - Kim, Elizabeth

AU - Tanner, Amy

AU - Michel, Patrik

AU - Eskandari, Ashraf

AU - Oddo, Mauro

AU - Suys, Tamarah

AU - Remillard, Suzette

AU - Cordier, Maria

AU - Brown, Robert

AU - Jasak, Sara

AU - McCullough, Louise

AU - Brautigam, Robert

AU - Alexandrov, Andrei

AU - Sisson, April

AU - Albright, Karen

AU - Broessner, Gregor

AU - Schmutzhard, Erich

AU - Escioglou, Elissanet

AU - Jones, William

AU - Poisson, Sharon

AU - Simpson, Jennifer

AU - Shah, Qaisar

AU - Jonczak, Karin

AU - Bussinger, Patricia

AU - Lewandowski, Christopher

AU - Berry, Shannen

AU - Lundell, Annemarie

AU - Miller, Joseph B.

AU - Cruz-Flores, Salvador

AU - Holzer, Eve

AU - Torretta, Susan

AU - Brown, David

AU - Heim, Laura

AU - Smith, Carlos

AU - Kelley, Chip

AU - Greer, David

AU - Marcolini, Evadne G.

AU - Gilmore, Emily J.

AU - Seton, Austin

AU - Rutledge, Neil

AU - McBee, Del

AU - Khanna, Anna

AU - Warren, Sonisha

AU - Wilsom, Christina

AU - Hedna, Vishnumurthy Shushrutha

AU - Rosado, Christian

AU - Kizza, Rosie

AU - O’phelan, Kristine

AU - Escobar, Andrea

AU - Merenda, Amedeo

AU - Barcena, Juan Perez

AU - Malik, Amer

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

KW - hypothermia

KW - intention to treat analysis

KW - ischemic stroke

KW - neuroprotection

KW - pneumonia

KW - stroke

KW - therapeutics

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U2 - 10.1161/STROKEAHA.116.014200

DO - 10.1161/STROKEAHA.116.014200

M3 - Article

C2 - 27834742

AN - SCOPUS:84995489913

SN - 0039-2499

VL - 47

SP - 2888

EP - 2895

JO - Stroke

JF - Stroke

IS - 12

ER -

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

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