Quelling of Excitotoxicity in Acute Stroke With Ketamine (QUEST-KETA)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam injection; Other: Normal Saline

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Sudhir Aggarwal, MD, PhD; Phone Number: 4844132572; Email: saggarwal@lowermerionneurology.com

Study Locations

• United States
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
      • Contact: Sudhir Aggarwal, MD, PhD; Phone Number: 484-413-2572; Email: saggarwal@lowermerionneurology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Drug; Will receive Ketamine infusion, and Midazolam (Versed).	Drug: Ketamine; IV infusion; Drug: Midazolam injection; Injection; Other Names: Versed
Placebo Comparator: Placebo; Will receive Normal saline infusion and Midazolam (Versed).	Drug: Midazolam injection; Injection; Other Names: Versed; Other: Normal Saline; IV infusion

What is the study measuring?

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
All cause mortality		90 days
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
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

Collaborators and Investigators

• Sponsor: Lower Merion Neurology Research Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 14, 2017
• First Submitted That Met QC Criteria: July 18, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Stroke, Neuroprotection, Ketamine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: LMNRF-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No