Quelling of Excitotoxicity in Acute Stroke With Ketamine

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Quelling of Excitotoxicity in Acute Stroke With Ketamine

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Ketamine
* Other: Normal Saline
* Drug: Midazolam injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients who are 18 years or older, presenting or admitted to the study site with acute ischemic stroke, up to 24 hours since their last known well time An MRI evidence of acute ischemic infarct on the diffusion-weighted imaging with ADC correlate Pre-stroke modified Rankin scale of 0-2 Patient should be willing to participate in the study by providing a written consent himself/herself or through a proxy. Exclusion Criteria: Eligibility to receive IV Alteplase or intra-arterial thrombectomy/embolectomy Longer than 24 hours since last known well time Pre-stroke modified Rankin scale of 3 or above. Pregnant or lactating females Pre-existing psychiatric illness Intracranial hemorrhage of any type at presentation Seizure at onset of symptoms Sustained uncontrolled hypertension defined as Systolic Blood pressure greater than 185 mmHg or Diastolic Blood Pressure greater than 110 mmHg, despite administration of antihypertensive medications Known hypersensitivity or adverse reaction to prior administration of Ketamine Inability/refusal to provide consent by the patient or through a proxy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Drug<br>Will receive Ketamine infusion, and Midazolam (Versed). | Drug: Ketamine<br>* IV infusion<br>Drug: Midazolam injection<br>* Injection<br>* Other names: Versed;|
| Placebo Comparator: Placebo<br>Will receive Normal saline infusion and Midazolam (Versed). | Other: Normal Saline<br>* IV infusion<br>Drug: Midazolam injection<br>* Injection<br>* Other names: Versed;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | On day 1 and at 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Barthel's index | An improvement of 10 or more points in Barthel's index will be considered a favorable outcome. | On day 1, and at 90 days | 
| NIH stroke scale score |  | On day 1, day 4 or discharge whichever is earlier, and at 90 days | 
| Depression score using the PHQ9 questionnaire |  | On day 1, and day 4 or discharge whichever is earlier. | 
| Infarct volumes | Measured from the DWI-MRI and/or CT images | On day 1, and day 4 or discharge whichever is earlier | 
| All cause mortality |  | 90 days | 
| Stroke-related mortality |  | 90 days | 
| Symptomatic intracranial hemorrhage |  | Day 4 or discharge whichever is earlier | 
| Deterioration in neurologic status | Increase of 4 or more points in the NIH stroke scale | Up to day 4 or discharge whichever is earlier | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Neuroprotection, Ketamine