Clinical trial NCT03223220: Quelling of Excitotoxicity in Acute Stroke With Ketamine
Official title: Quelling of Excitotoxicity in Acute Stroke With Ketamine
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute Ischemic Stroke
Keywords: Stroke, Neuroprotection, Ketamine
Lead sponsor: Lower Merion Neurology Research Foundation
Sponsor class: OTHER
First posted: 2017-07-21
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in weighted modified Rankin scale score between day 1 and 90 will be assessed.
timeFrame: On day 1 and at 90 days
Secondary outcomes:
measure: Barthel's index
timeFrame: On day 1, and at 90 days
measure: NIH stroke scale score
timeFrame: On day 1, day 4 or discharge whichever is earlier, and at 90 days
measure: Depression score using the PHQ9 questionnaire
timeFrame: On day 1, and day 4 or discharge whichever is earlier.
measure: Infarct volumes
timeFrame: On day 1, and day 4 or discharge whichever is earlier
measure: All cause mortality
timeFrame: 90 days
measure: Stroke-related mortality
timeFrame: 90 days
measure: Symptomatic intracranial hemorrhage
timeFrame: Day 4 or discharge whichever is earlier
measure: Deterioration in neurologic status
timeFrame: Up to day 4 or discharge whichever is earlier
Other outcomes:
Locations:
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
Study officials:
References: