Mild Hypothermia in Acute Ischemic Stroke

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Katja Piironen, Helsinki University
ClinicalTrials.gov Identifier:
NCT00987922
First received: September 30, 2009
Last updated: September 17, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Brain Ischemia
Device: Hypothermia
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Helsinki University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 36
Study Start Date: July 2007
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypothermia Device: Hypothermia
Hypothermia to core temperature of 35C for 12 hours, rewarming rate 0.2C until the patient reaches 36.8C
No Intervention: Control

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00987922

Sponsors and Collaborators
Helsinki University
Investigators
Principal Investigator: Markku Kaste, MD, PhD Helsinki University Central Hospital
  More Information

No publications provided by Helsinki University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Katja Piironen, MD, Helsinki University
ClinicalTrials.gov Identifier: NCT00987922     History of Changes
Other Study ID Numbers: FI-HUCH-220424
Study First Received: September 30, 2009
Last Updated: September 17, 2011
Health Authority: Finland: Ethics Committee

Keywords provided by Helsinki University:
Stroke
Acute
Infarction
Ischemic
Thrombolysis
Mild
Hypothermia

Additional relevant MeSH terms:
Brain Ischemia
Hypothermia
Ischemia
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Body Temperature Changes
Signs and Symptoms
Pathologic Processes

ClinicalTrials.gov processed this record on April 15, 2014