Ketamine for Intensive Care Unit Patients

(KANINE Trial)

Not yet recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: McMaster University

Must be taking: Non-ketamine sedatives

Must not be taking: Neuromuscular blockers

Disqualifiers: Brain injury, Hypertension, Schizophrenia, Liver failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of ketamine for ICU patients on breathing machines. Ketamine helps with sedation and pain relief, potentially reducing the need for other medications with more side effects. The trial will compare ketamine to a placebo (a harmless substance resembling ketamine) to determine which works better. It seeks adult ICU patients who have been on a breathing machine for less than three days and are not experiencing severe brain injuries, burns, or other specific conditions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advances.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants will be receiving non-ketamine continuous sedative infusions, so you may continue with those if applicable.

Is there any evidence suggesting that ketamine is likely to be safe for ICU patients?

Research has shown that using ketamine in the ICU does not increase death rates compared to other treatments. Some studies suggest it might even alleviate confusion related to ICU stays. However, side effects can include confusion, changes in blood pressure, and increased saliva production. Ketamine's approval for use in emergency and operating rooms demonstrates its safety in certain medical settings. This ongoing study examines whether ketamine is safe and beneficial for ICU patients requiring breathing machines. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for managing pain and agitation in ICU patients, which often include opioids and benzodiazepines, ketamine offers a unique approach. Ketamine is an NMDA receptor antagonist, which means it works by blocking certain receptors in the brain to prevent and reduce pain and discomfort. This mechanism is different from most current options, which can lead to significant side effects like respiratory depression. Researchers are excited about ketamine because it not only provides rapid relief but also has the potential to improve patient outcomes without the heavy sedation often seen with traditional sedatives.

What evidence suggests that ketamine might be an effective treatment for ICU patients on a breathing machine?

Research has shown that ketamine can aid in sedation and pain relief for ICU patients. In this trial, participants will receive either a continuous ketamine infusion or a placebo. Some studies suggest ketamine might reduce confusion in these patients, but further research is needed for confirmation. Evidence indicates ketamine may improve survival rates, particularly in younger patients and those with conditions like breathing problems. However, results are mixed regarding its effects on hospital stays and ventilator use, with some studies noting higher costs and longer stays. Overall, ketamine is already used for pain relief and anesthesia and may offer benefits for ICU patients requiring sedation. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adult ICU patients on ventilators early in their stay, excluding those with brain injuries, uncontrolled high blood pressure, schizophrenia, severe liver failure, palliative care status, paralysis medication use, tracheostomy breathing through the neck, ketamine allergy, recent liver transplant or who are pregnant/breastfeeding.

Inclusion Criteria

I have been on a ventilator for less than 3 days.

I have been on a breathing machine through a tube for over a day.

I am on a continuous sedative drip that is not ketamine.

Exclusion Criteria

History of schizophrenia

My blood pressure is very high (>180/100 mmHg).

I need a strong medication to maintain my blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either adjunctive ketamine infusion or placebo while on a breathing machine in the ICU

Up to 14 days

Continuous monitoring in ICU

Follow-up

Participants are monitored for outcomes such as delirium, sedative use, and PTSD symptoms post-ICU discharge

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview The KANINE RCT tests if adding ketamine to usual sedation care improves outcomes for mechanically ventilated ICU patients. It's a blinded study across Canadian ICUs where participants are randomly given either ketamine or a saline placebo without knowing which one they receive.

How Is the Trial Designed?

Group I: Ketamine Experimental Treatment 1 Intervention

Continuous ketamine infusion (0.50 mg/kg/hour)

Group II: Placebo Placebo Group 1 Intervention

Normal Saline Placebo

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11002615/

The impact of ketamine on outcomes in critically ill patients Ketamine reduces delirium rate, but this needs to be confirmed by new randomized controlled trials. Conclusions are limited by the risk of bias.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38046843/

Efficacy and safety of ketamine in mechanically ventilated ... Conclusions: Ketamine is used in mechanically ventilated ICU patients with several potentially positive clinical effects. However, it has a ...

3. journals.lww.com journals.lww.com/ccejournal/fulltext/2024/07000/use_of_early_ketamine_sedation_and_association.1.aspx

Use of Early Ketamine Sedation and Association With... Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days.

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0320047

Association between ketamine use and mortality in critically ill ... Ketamine was associated with lower 14-day mortality rates among younger patients, those with acute respiratory distress syndrome, and norepinephrine users.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9354105/

Ketamine use in critically ill patients: a narrative review - PMC Research has demonstrated the efficacy of its use on anesthesia, pain, palliative care, and intensive care.

6. journals.lww.com journals.lww.com/eccm/fulltext/2025/09000/ketamine_use_in_adult_intensive_care_unit__a.6.aspx

Ketamine use in adult intensive care unit: a narrative... Some data suggest that ketamine may reduce the incidence of ICU delirium and aid in managing refractory psychiatric conditions; however, concerns about adverse ...

7. journals.plos.org journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0320047&type=printable

Association between ketamine use and mortality in critically ill ... Our hypothesis was that ketamine administration would be associ- ated with improved survival in these patients. Materials and methods. Database.

8. nature.com nature.com/articles/s41598-025-91016-w

a double-blind, randomized controlled clinical trial Secondary outcomes were the duration of ventilation support, length of intensive care unit (ICU) stay, 28-day mortality. We enrolled 80 ...