Mild Hypothermia in Acute Ischemic Stroke

Phase 2

Completed

• Conditions: Brain Ischemia
• Interventions: Device: Hypothermia

• Registration Number: NCT00987922
• Lead Sponsor: University of Helsinki

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2009-09-30
• Study First Submitted QC: 2009-09-30
• Study First Posted: 2009-10-01
• Status Verified: 2011-09
• Primary Completion: 2011-09
• Study Completion: 2011-09
• Last Update Submitted: 2011-09-17
• Last Update Posted: 2011-09-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Acute ischemic hemispheric stroke treated with Actilyse(tPA)-thrombolysis according to Meilahti protocol
• NIHSS 7-20 (after thrombolysis) or a significant paresis of arm or leg (NIHSS 3, no movement against gravity) or a significant dysphasia (NIHSS 2-3) despite of the total NIHSS score
• Symptom onset within 6 hour

Exclusion Criteria

• Platelet count < 75,000/mm3
• Known coagulopathy (INR spontaneously >1.5)
• Hemodynamical unstability
• Recent history of angina pectoris or acute myocardial infarction
• Sepsis within 72 hours
• Pregnancy
• Pre-existing neurological disability with modified Rankin Scale Score>2
• Known allergy or intolerance to buspirone, dexmedetomidine, meperidine
• Intracranial hemorrhage in brain CT scan
• Intracranial mass lesion (i.e., abscess, tumor, or infection)
• Participation in an other therapy trial within last 3 months
• Hypothermia- treatment cannot be initiated within 6 hours of symptom onset
• Protocol violation in thrombolytic therapy
• Any condition where researchers assume that the patient is not suitable (must be reasoned)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hypothermia	Hypothermia	-

Primary Outcome Measures

Name	Time	Method
The proportion of patients maintaining temperature below 36.0°C 80% of the 12-hour hypothermia period.	12 hours

Secondary Outcome Measures

Name	Time	Method
The incidence of intracerebral hemorrhage, infections, hemodynamically significant cardiac arrhythmias, severe disturbance of electrolytes and fluid balance, thrombocytopenia, and serious adverse events	14 days
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.	3 months
The proportion of modified Rankin Scale-responders (mRS 0-2), Barthel Index, NIHSS, Glasgow Outcome Scale	3 months
Neuropsychological tests	3 months
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)	3-7 days