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 Jane Hess5,
- James Grotta5 and
- Patrick D Lyden13
© Hemmen et al.; licensee BioMed Central Ltd. 2012
Published: 7 June 2012
The ICTuS trial showed feasibility of endovascular hypothermia for acute ischemic stroke ; ICTuS L confirmed safety and feasibility of endovascular hypothermia during thrombolysis . 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.
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.
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.
ICTuS 2/3 is the largest trial of endovascular hypothermia for acute stroke currently running. There appear to be no safety or feasibility concerns.
NINDS grants P50NS5044148 (UCSD) and P50NS044227 (Houston).
- 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.2005.01.001View ArticlePubMedGoogle Scholar
- 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.110.592295PubMed CentralView ArticlePubMedGoogle Scholar
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