Mild Hypothermia in Acute Ischemic Stroke
Hypothesis: Mild hypothermia using non-invasive temperature management system in a stroke unit is safe and feasible in spontaneously breathing, alteplase-thrombolyzed patients with acute ischemic stroke.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Mild Hypothermia in Acute Ischemic Stroke After Thrombolytic Therapy: a Prospective,Open,Randomized,Single-center,Safety and Feasibility Study|
- The proportion of patients maintaining temperature below 36.0°C 80% of the 12-hour hypothermia period. [ Time Frame: 12 hours ] [ Designated as safety issue: No ]
- The incidence of intracerebral hemorrhage, infections, hemodynamically significant cardiac arrhythmias, severe disturbance of electrolytes and fluid balance, thrombocytopenia, and serious adverse events [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
- All-cause mortality during acute phase (7 days), 1 month, and 3 month follow-up; and readmission to hospital for any reason within 3-months. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- The proportion of modified Rankin Scale-responders (mRS 0-2), Barthel Index, NIHSS, Glasgow Outcome Scale [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Neuropsychological tests [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Size of infarction in MRI, and grading of the possible hemorrhagic transformation according to SITS scale (MRI includes scout images, DWI, T1, T2, FLAIR, T2*, and MR angiography) [ Time Frame: 3-7 days ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2007|
|Study Completion Date:||September 2011|
|Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
Hypothermia to core temperature of 35C for 12 hours, rewarming rate 0.2C until the patient reaches 36.8C
|No Intervention: Control|
Fever is associated with higher stroke mortality and poor outcome, but it is yet unknown whether this association is causative or epiphenomenal.
In temporary brain ischemia rodent models hypothermia results in a significant increase in the number of surviving neurons and smaller infarction size as measured with histological examination after death.
Therapeutic effect has been shown in clinical trials in comatose cardiac arrest patients and newborn infants with perinatal hypoxic-ischemic brain injury.
Design: A prospective, open, randomized single-center study.
Study population: 36 patients, 18-85 years of age presenting with symptoms of acute ischemic hemispheric stroke with persisting significant neurological deficit (NIHSS 7-20 or NIHSS 2 for dysphasia or NIHSS 3 for paralysis of upper or lower limb) at 2 hours after thrombolysis.
Method: Patients are randomized to hypothermia- or control-group via randomization envelopes. Patients assigned to receive hypothermia are cooled to a core temperature of 35°C for 12 hours by means of a non-invasive temperature management system and cold i.v. fluids. Induction of hypothermia is initiated within 6 hours of symptom onset. After 12 hours of successful cooling the target temperature is gradually raised to achieve slow re-warming of 0.2°C/h until the core temperature reaches 36.8°C.
Patients are breathing spontaneously and shivering is controlled with following medication; dexmedetomidine 0.2-0.7 µg/kg/h (i.v.), buspirone 5-20 mg x 3 (nasogastric tube), and meperidine 25mg (i.v.) when needed.
Core temperature, blood pressure (BP), oxygen saturation, ECG and EEG are measured continuously and registered hourly. Blood tests will be taken before, during and after hypothermia. Brain CT will be controlled when normothermia is reached, no later than 30 hours from symptom onset. Brain MRI will be performed 3-7 days from symptom onset.