Quelling of Excitotoxicity in Acute Stroke With Ketamine

Phase 2

Not yet recruiting

• Conditions: Acute Ischemic Stroke
• Interventions: Other: Normal Saline; Drug: Ketamine; Drug: Midazolam injection

• Registration Number: NCT03223220
• Lead Sponsor: Lower Merion Neurology Research Foundation

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-07-14
• Study First Submitted QC: 2017-07-18
• Study First Posted: 2017-07-21
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-14
• Last Update Posted: 2023-12-18
• Study Start: 2024-07-01
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Midazolam injection	Will receive Normal saline infusion and Midazolam (Versed).
Placebo	Normal Saline	Will receive Normal saline infusion and Midazolam (Versed).
Study Drug	Midazolam injection	Will receive Ketamine infusion, and Midazolam (Versed).
Study Drug	Ketamine	Will receive Ketamine infusion, and Midazolam (Versed).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Infarct volumes	On day 1, and day 4 or discharge whichever is earlier	Measured from the DWI-MRI and/or CT images
Symptomatic intracranial hemorrhage	Day 4 or discharge whichever is earlier
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.
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.
All cause mortality	90 days
Stroke-related mortality	90 days
Deterioration in neurologic status	Up to day 4 or discharge whichever is earlier	Increase of 4 or more points in the NIH stroke scale

Trial Locations

Locations (1)

Lankenau Medical Center; 🇺🇸 Wynnewood, Pennsylvania, United States