The investigators plan to undertake a phase II study to investigate the efficacy and side effects of intravenous ketamine to reduce neuroexcitotoxicity, and thus provide neuroprotection in patients diagnosed with acute ischemic stroke.
After obtaining informed consent, patients enrolled in the 'study drug' arm of the trial will receive Ketamine (1 mg/ml solution prepared in normal saline) infusion at a rate of 20 mg/h for a period of 24 hours. The infusion will start at a rate of 5 mg/h, and then gradually tapered up during the first 3 hours by 5 mg an hour. Similarly, the infusion rate will be gradually tapered down at a rate of 5 mg/h during the last 3 hours of infusion. The patients randomized to the 'placebo arm' of the trial will receive normal saline infusion at the same rates. In order to prevent the psychogenic adverse effects associated with Ketamine, the patients will be administered Midazolam at a dose of 1 mg IV every 4 hours. Midazolam will also be administered at the same rate to the patients randomized to the placebo arm. Blood Ketamine levels will be measured before starting the treatment, and daily while the infusion is on. While receiving treatment, the patients will be admitted to the telemetry floor in the hospital, on a monitored bed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
120
Lankenau Medical Center
Wynnewood, Pennsylvania, United States
Change in weighted modified Rankin scale score between day 1 and 90 will be assessed.
An improvement of 2 in mRS score will be considered favorable outcome.
Time frame: On day 1 and at 90 days
Barthel's index
An improvement of 10 or more points in Barthel's index will be considered a favorable outcome.
Time frame: On day 1, and at 90 days
NIH stroke scale score
Time frame: On day 1, day 4 or discharge whichever is earlier, and at 90 days
Depression score using the PHQ9 questionnaire
Time frame: On day 1, and day 4 or discharge whichever is earlier.
Infarct volumes
Measured from the DWI-MRI and/or CT images
Time frame: On day 1, and day 4 or discharge whichever is earlier
All cause mortality
Time frame: 90 days
Stroke-related mortality
Time frame: 90 days
Symptomatic intracranial hemorrhage
Time frame: Day 4 or discharge whichever is earlier
Deterioration in neurologic status
Increase of 4 or more points in the NIH stroke scale
Time frame: Up to day 4 or discharge whichever is earlier
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