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Volume 16 Supplement 2

Update on therapeutic temperature management

Phase 2/3 study of intravenous thrombolysis and hypothermia for acute treatment of ischemic stroke (ICTuS 2/3)

Critical Care volume 16, Article number: A13 (2012) Cite this article

Background

The ICTuS trial showed feasibility of endovascular hypothermia for acute ischemic stroke [1]; ICTuS L confirmed safety and feasibility of endovascular hypothermia during thrombolysis [2]. The ICTuS 2/3 study seeks to determine whether the combination of thrombolysis and hypothermia is superior to thrombolysis alone for the treatment of acute ischemic stroke. A phase 2 study will include 450 patients to assess the safety of various protocol changes, to demonstrate sufficient recruitment, and to allow an interim analysis for futility. If pre-specified milestones are achieved the study will be enlarged to a 1,800-patient phase 3 efficacy study.

Methods

This is a prospective, randomized, single-blind, multicenter phase 2/3 study. We aim to include ischemic stroke patients treated within 3 hours of symptom onset with IV tPA (according to FDA or EMEA protocol), NIHSS ≥7 and ≤20, age 22 to 80. Patients are randomly assigned to either hypothermia permissively targeted to 33°C or normothermia. Favorable outcome is defined as a 90-day Modified Rankin score (mRS) of 0 or 1. Secondary outcome measures are: 90-day NIHSS, Barthel Index (BI), mortality, shift analysis of the mRS, global odds ratio of mRS, BI, NIHSS, incidence of symptomatic intracranial hemorrhage and 90-day Montreal Cognitive Assessment. An interim analysis for futility is planned near the end of phase 2. In addition to futility, analyses will assess the frequency of target temperature reached within 6 hours from symptom, pneumonia rate, safety profile of iced saline infusion and study-wide average enrollment rate.

Results

The study team initiated 11 study sites in the USA and two in Europe. Enrolment began in December 2010. Currently, 37 subjects are enrolled. A full DSMB review of experience to date allowed the study to continue enrollment. A safety review after the first 50 patients is expected in late 2012.

Conclusions

ICTuS 2/3 is the largest trial of endovascular hypothermia for acute stroke currently running. There appear to be no safety or feasibility concerns.

References

  1. Lyden PD, Allgren RL, Ng K, Akins P, Meyer B, Al-Sanani F, Lutsep H, Dobak J, Matsubara BS, Zivin J: Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience. J Stroke Cerebrovasc Dis 2005, 14: 107-114. 10.1016/j.jstrokecerebrovasdis.2005.01.001

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  2. Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, Wijman CA, Rapp KS, Grotta JC, Lyden PD: Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke 2010, 41: 2265-2270. 10.1161/STROKEAHA.110.592295

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Acknowledgements

NINDS grants P50NS5044148 (UCSD) and P50NS044227 (Houston).

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Authors and Affiliations

  1. UCSD Medical Center, San Diego, CA, USA

    Thomas Hemmen, Karen Rapp, Rema Raman & Julie Jurf

  2. Sarasota Memorial Hospital, Sarasota, FL, USA

    Mauricio Concha

  3. University Hospital Innsbruck, Austria

    Gregor Brössner & Erich Schmutzhard

  4. Scripps Mercy Hospital, San Diego, CA, USA

    Gilda Tafreshi

  5. University of Texas, Houston, TX, USA

    Vivek Misra, Mary Jane Hess & James Grotta

  6. St Louis University, St Louis, MO, USA

    Salvador Cruz-Flores

  7. University of Erlangen, Germany

    Rainer Kollmar

  8. Hoag Hospital, Newport Beach, CA, USA

    David Brown

  9. North Memorial Hospital, Robbinsdale, MN, USA

    Irfan Altafullah

  10. University of Lausanne, Switzerland

    Patrik Michel

  11. University of Alabama, Birmingham, AL, USA

    Andrei Alexandrov

  12. St Joseph Hospital, Tampa, FL, USA

    Carlos Smith

  13. Cedars Sinai Medical Center, Los Angeles, CA, USA

    Patrick D Lyden

Authors
  1. Thomas Hemmen
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  2. Karen Rapp
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  3. Rema Raman
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  4. Mauricio Concha
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  5. Gregor Brössner
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  6. Erich Schmutzhard
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  7. Gilda Tafreshi
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  8. Vivek Misra
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  9. Salvador Cruz-Flores
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  10. Rainer Kollmar
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  11. David Brown
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  12. Irfan Altafullah
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  13. Patrik Michel
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  14. Andrei Alexandrov
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  15. Carlos Smith
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  16. Julie Jurf
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  17. Mary Jane Hess
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  18. James Grotta
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  19. Patrick D Lyden
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Hemmen, T., Rapp, K., Raman, R. et al. Phase 2/3 study of intravenous thrombolysis and hypothermia for acute treatment of ischemic stroke (ICTuS 2/3). Crit Care 16 (Suppl 2), A13 (2012). https://doi.org/10.1186/cc11271

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