This article is part of the supplement: Update on therapeutic temperature management

Meeting abstract

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

Thomas Hemmen1*, Karen Rapp1, Rema Raman1, Mauricio Concha2, Gregor Brössner3, Erich Schmutzhard3, Gilda Tafreshi4, Vivek Misra5, Salvador Cruz-Flores6, Rainer Kollmar7, David Brown8, Irfan Altafullah9, Patrik Michel10, Andrei Alexandrov11, Carlos Smith12, Julie Jurf1, Mary J Hess5, James Grotta5 and Patrick D Lyden13

  • * Corresponding author: Thomas Hemmen

Author Affiliations

1 UCSD Medical Center, San Diego, CA, USA

2 Sarasota Memorial Hospital, Sarasota, FL, USA

3 University Hospital Innsbruck, Austria

4 Scripps Mercy Hospital, San Diego, CA, USA

5 University of Texas, Houston, TX, USA

6 St Louis University, St Louis, MO, USA

7 University of Erlangen, Germany

8 Hoag Hospital, Newport Beach, CA, USA

9 North Memorial Hospital, Robbinsdale, MN, USA

10 University of Lausanne, Switzerland

11 University of Alabama, Birmingham, AL, USA

12 St Joseph Hospital, Tampa, FL, USA

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

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Critical Care 2012, 16(Suppl 2):A13 doi:10.1186/cc11271


The electronic version of this article is the complete one and can be found online at: http://ccforum.com/content/16/S2/A13


Published:7 June 2012

© 2012 Hemmen et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Acknowledgements

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

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. PubMed Abstract | Publisher Full Text OpenURL

  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. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL