Acute Ischemic Stroke
Conditions
Keywords
Stroke, Neuroprotection, Ketamine
Brief summary
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
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.
Interventions
DRUGKetamine
IV infusion
OTHERNormal Saline
IV infusion
DRUGMidazolam injection
Injection
Sponsors
Lower Merion Neurology Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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 2. An MRI evidence of acute ischemic infarct on the diffusion-weighted imaging with ADC correlate 3. Pre-stroke modified Rankin scale of 0-2 4. Patient should be willing to participate in the study by providing a written consent himself/herself or through a proxy.
Exclusion criteria
1. Eligibility to receive IV Alteplase or intra-arterial thrombectomy/embolectomy 2. Longer than 24 hours since last known well time 3. Pre-stroke modified Rankin scale of 3 or above. 4. Pregnant or lactating females 5. Pre-existing psychiatric illness 6. Intracranial hemorrhage of any type at presentation 7. Seizure at onset of symptoms 8. 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 9. Known hypersensitivity or adverse reaction to prior administration of Ketamine 10. Inability/refusal to provide consent by the patient or through a proxy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in weighted modified Rankin scale score between day 1 and 90 will be assessed. | On day 1 and at 90 days | An improvement of 2 in mRS score will be considered favorable outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | On day 1, and day 4 or discharge whichever is earlier | Measured from the DWI-MRI and/or CT images |
| Barthel's index | On day 1, and at 90 days | An improvement of 10 or more points in Barthel's index will be considered a favorable outcome. |
| Stroke-related mortality | 90 days | — |
| Symptomatic intracranial hemorrhage | Day 4 or discharge whichever is earlier | — |
| Deterioration in neurologic status | Up to day 4 or discharge whichever is earlier | Increase of 4 or more points in the NIH stroke scale |
| All cause mortality | 90 days | — |
Countries
United States
Contacts
Primary ContactSudhir Aggarwal, MD, PhD
Outcome results
None listed