Quelling of Excitotoxicity in Acute Stroke With Ketamine

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.

Intervention / Treatment

  • Ketamine (DRUG)
    IV infusion
  • Normal saline (OTHER)
    IV infusion
  • Midazolam injection (DRUG)
    Injection

Condition or Disease

  • Acute Ischemic Stroke

Phase

  • Phase 2
  • Phase 3

    • Study Design

    Study type: INTERVENTIONAL
    Status: Not yet recruiting
    Study results: No Results Available
    Age: 18 Years and older   (Adult, Older Adult)
    Enrollment: 120 (ESTIMATED)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Jan 01, 2023 ESTIMATED
    Primary Completion: Dec 31, 2024 ESTIMATED
    Completion Date: Dec 31, 2025 ESTIMATED
    Study First Posted: Jul 21, 2017 ACTUAL
    Results First Posted: Aug 31, 2020
    Last Updated: Oct 12, 2022

    Sponsors / Collaborators

    Lead Sponsor: Lower Merion Neurology Research Foundation
    Responsible Party: N/A

    Location

    Wynnewood, Pennsylvania, USA

    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.

    Participant Groups

    • Will receive Ketamine infusion, and Midazolam (Versed).

    • Will receive Normal saline infusion and Midazolam (Versed).

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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

    • An improvement of 2 in mRS score will be considered favorable outcome.

    Secondary Outcomes

    • An improvement of 10 or more points in Barthel's index will be considered a favorable outcome.

    • 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.

    • Measured from the DWI-MRI and/or CT images

    • All cause mortality 90 days
    • Stroke-related mortality 90 days
    • Symptomatic intracranial hemorrhage Day 4 or discharge whichever is earlier

    • Increase of 4 or more points in the NIH stroke scale

    More Details

    NCT Number: NCT03223220
    Acronym: QUEST-KETA
    Other IDs: LMNRF-001
    Study URL: https://clinicaltrials.gov/study/NCT03223220
    Last updated: Sep 29, 2023