Ketamine Sedation in the ICU (KANINE) RCT

NCT06767358 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 202405KTMN
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 3

Brief Summary

Sedation is given to intensive care unit (ICU) patients to treat discomfort, anxiety, agitation, and to help facilitate care, particularly when they require a breathing tube. Sedation is very commonly used in the ICU with North American data showing almost 40% of ICU patients get sedation to help when they are requiring a breathing machine. Various medications can be given intravenously to provide sedation in the ICU but there are side-effects associated with each such as decreasing a patient's own drive to breathe, and delirium or acute confusion, both of which are associated with worse outcomes. Also, most drugs used for sedation don't treat pain. As a result, many ICU patients are also given narcotics for pain control which can result in tolerance, dependence, and withdrawal. Ketamine is a sedating medication that also treats pain and is often used in the Emergency Department and in the Operating Room but for whatever reason is not commonly used in the ICU. The investigators are proposing a study to examine the usefulness and safety of adding an intravenous infusion of ketamine to usual care in adult patients that are on a breathing machine in the ICU. Study Methods The KANINE study is being done at hospitals across Ontario, Canada. It is a randomized controlled trial which means patients will be randomized (akin to a coin flip) to receive ketamine or usual care without ketamine. The study will be blinded which means that neither patients or the doctors will know if the patient is getting ketamine or not, those that get randomized to usual care without ketamine will get an intravenous solution that looks the same as the ketamine infusion. This is important to make sure the results aren't biased in any way. The investigators will include adult ICU patients on a breathing machine who are early in their ICU admission. As most patients will be unconscious, the investigators will ask substitute decision makers (families or caregivers) of patients for informed consent prior to the study commencing. Regardless of whether patients get randomized to ketamine or not, the investigators will make sure that all patients will be adequately sedated and have their pain managed as per usual care. Setting This study will be performed in adult ICUs across Canada. Population The investigators will include adults admitted to the ICU on a breathing machine and expected to remain mechanically ventilated beyond the calendar day after randomization. The investigators will exclude patients if: (i) they were admitted with a brain bleed, traumatic brain injury, or stroke; (ii) Admitted with uncontrolled high blood pressure; (iii) admitted with status asthmaticus; (iv); admitted to the ICU with partial thickness burns greater than 10% total body surface area or any full thickness burns; (v) if they have a history of schizophrenia; (vi) if they have very bad liver failure; (vii) if they are palliative or only for comfort care; (viii) if they are requiring very high doses of blood pressure support medication to increase their blood pressure; (ix) if they are receiving a medication that causes paralysis, sometimes used in patients with very bad lung disease; (x) if they have a tracheostomy which means a whole in their neck that they breathe through; (xi) if they are allergic to ketamine; (xii) if they've had a liver transplant in the last month; (xiii) if they are pregnant or breast-feeding. Outcomes The investigators will follow all the study patients to see if their outcomes are different depending on whether they get randomized to ketamine or not. The investigators will capture how much time they are on the breathing machine, whether they survive or die, how long they stay in the ICU and whether they require a tracheostomy which is a procedure often done on patients who require the breathing machine over a prolonged period of time. The investigators will also capture how often they get delirious and for those that get delirious how long it lasts for. The investigators will capture how much of other sedating medications study patients use such as antipsychotics and benzodiazepines. The investigators will capture outcomes such as how often study patients get post-traumatic stress disorder after leaving the ICU and how well their pain relief is addressed during their ICU stay. Finally, the investigators will capture side effects related to ketamine or other sedating drug use.

Conditions

Mechanical Ventilation; Critically Ill Intensive Care Unit Patients

Keywords

sedation; mechanical ventilation; intensive care unit; critically ill

Outcome Measures

Primary Outcomes (3)

• Feasibility: Recruitment Rate

  Feasibility will be judged by the 3 outcomes of recruitment rate, consent rate, and protocol adherence. We define a successful recruitment rate of 0.5 patients per centre per month over the duration of the trial.

  3 months

• Feasibility: Consent Rate

  This will be judged by the 3 outcomes of recruitment rate, consent rate, and protocol adherence. We will define \>75% consent rate as successful.

  3 months

• Feasibility: Protocol Adherence

  This will be judged by the 3 outcomes of recruitment rate, consent rate, and protocol adherence. We will define ≥75% protocol adherence as successful.

  3 months

Secondary Outcomes (16)

• Ventilator-free Days at 28 days

  28 Days

• 28-day mortality

  28 Days

• ICU Mortality

  3 months

• ICU Length of Stay

  3 months

• Number of Participants receiving a Tracheostomy

  3 months

Study Arms (2)

Ketamine

EXPERIMENTAL

Continuous ketamine infusion (0.50 mg/kg/hour)

Drug: ketamine hydrochloride

Placebo

PLACEBO COMPARATOR

Normal Saline Placebo

Other: Normal saline placebo

Interventions

ketamine hydrochloride DRUG

Continuous adjunctive ketamine infusion at a fixed dose of 0.50mg/kg/hour

Ketamine

Normal saline placebo OTHER

Normal saline placebo infusion

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥ 18 years) admitted to the ICU
• Receiving invasive mechanical ventilation and expected to remain mechanically ventilated beyond the calendar day after randomization
• Mechanically ventilated for fewer than 3 days
• Receiving any non-ketamine continuous sedative infusion

You may not qualify if:

• Admitted with a primary diagnosis of intracranial hemorrhage, traumatic brain injury, or stroke
• Admitted with uncontrolled hypertension (SBP/DBP \> 180/100mmHg)
• Status asthmaticus
• Admitted to the ICU with partial thickness burns \> 10% total body surface area or any full thickness burns
• Schizophrenia
• End-stage Liver Failure (Child-Pugh C)
• Requiring an equivalent of norepinephrine at a dose ≥1mcg/kg/min
• Undergoing palliation or comfort care
• On neuromuscular blocking agent
• Pre-existing tracheostomy
• Hypersensitivity to Ketamine
• Liver transplantation in the last month
• Pregnant or breast-feeding

Sponsors & Collaborators

• McMaster University: lead

Study Sites (3)

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8V1C3, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

Location

MeSH Terms

Conditions

Critical Illness

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Statistician
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This RCT plans to study the use of an adjunctive ketamine infusion versus placebo in critically ill mechanically ventilated patients.

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: January 9, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)