Mild Hypothermia in Acute Ischemic Stroke

Brain Ischemia Clinical Trial

Official title:

Mild Hypothermia in Acute Ischemic Stroke After Thrombolytic Therapy: a Prospective,Open,Randomized,Single-center,Safety and Feasibility Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987922
• Other study ID #: FI-HUCH-220424
• Status: Completed
• Phase: Phase 2
• First received: September 30, 2009
• Last updated: September 17, 2011
• Start date: July 2007
• Est. completion date: September 2011

Study information

• Verified date: September 2011
• Source: Helsinki University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Ischemia
• Hypothermia

Intervention

Device:
• Hypothermia
Hypothermia to core temperature of 35C for 12 hours, rewarming rate 0.2C until the patient reaches 36.8C

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Helsinki University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of patients maintaining temperature below 36.0°C 80% of the 12-hour hypothermia period.		12 hours	No
Secondary	The incidence of intracerebral hemorrhage, infections, hemodynamically significant cardiac arrhythmias, severe disturbance of electrolytes and fluid balance, thrombocytopenia, and serious adverse events		14 days	Yes
Secondary	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	Yes
Secondary	The proportion of modified Rankin Scale-responders (mRS 0-2), Barthel Index, NIHSS, Glasgow Outcome Scale		3 months	No
Secondary	Neuropsychological tests		3 months	No
Secondary	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	Yes