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

Lower Merion Neurology Research Foundation

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Acute Ischemic Stroke

Treatments: Drug: Ketamine; Drug: Midazolam injection; Other: Normal Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT03223220

LMNRF-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 2 patient groups, including a placebo group

Study Drug

Experimental group

Description:

Will receive Ketamine infusion, and Midazolam (Versed).

Treatment:

Drug: Midazolam injection

Drug: Ketamine

Placebo

Placebo Comparator group

Description:

Will receive Normal saline infusion and Midazolam (Versed).

Treatment:

Drug: Midazolam injection

Other: Normal Saline