Ketamine + Propofol for Traumatic Brain Injury

(Ketamine Trial)

Overseen By Bradley Dengler, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Disqualifiers: Cardiovascular disease, Pregnancy, Prisoners, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of using ketamine (also known as Ketalar, Ketaset, and other names) with propofol to sedate patients with severe traumatic brain injuries in the ICU. Researchers aim to determine if this combination is better or as safe as the usual sedation treatments. Suitable participants have suffered a severe traumatic brain injury, are in the ICU, and require close brain pressure monitoring. As a Phase 4 trial, this research seeks to understand how this already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for ketamine and propofol?

Research has shown that using ketamine with propofol for sedation in patients with traumatic brain injuries is generally safe. Studies have found that ketamine does not increase the risk of death or raise intracranial pressure, which indicates safety. Some studies even suggest that ketamine might help lower this pressure.

This trial is in Phase 4, meaning the FDA has already approved ketamine and propofol for other uses, confirming their safety. This phase typically evaluates safety and effectiveness in larger groups. Therefore, the treatment is likely to be well-tolerated, but this trial will provide more specific information for brain injury cases. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using ketamine alongside propofol for traumatic brain injury because this combination could offer unique benefits compared to traditional options like fentanyl, morphine, or lorazepam. Unlike these standard treatments, which primarily focus on sedation and pain relief, ketamine has the added ability to potentially protect the brain by reducing inflammation and preventing further damage. Additionally, ketamine's fast-acting properties could lead to quicker improvements in patient outcomes. This combination aims to enhance recovery by targeting the brain's response to injury in a more comprehensive way.

What evidence suggests that this protocol is effective for traumatic brain injury?

In this trial, participants will receive either a combination of ketamine and propofol or standard of care analgosedation. Research has shown that "ketofol," a mix of ketamine and propofol, can improve blood flow and oxygen levels in the brain, which is vital for treating severe head injuries. Studies have found that ketamine helps lower intracranial pressure in these patients, preventing further brain damage. This combination is generally considered safe and may stabilize brain conditions more effectively than some other sedatives. ^{1 5 6 7 8}

Who Is on the Research Team?

Bradley Dengler, MD

Principal Investigator

Uniformed Services University of the Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with severe traumatic brain injury (TBI), indicated by a Glasgow Coma Scale score of 8 or less, who need intracranial pressure monitoring and are being treated in an ICU.

Inclusion Criteria

I have a severe brain injury and needed a device to monitor my brain.

I am in the ICU with a device to monitor brain pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either ketamine with propofol or standard of care analgosedation for sedation in the ICU

Up to 5 days

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

1 outpatient visit

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview

The study compares the safety of sedation using ketamine combined with propofol versus standard care options like propofol alone or other common sedatives used in intensive care settings for patients with severe TBI.

How Is the Trial Designed?

Group I: Ketamine with propofol Experimental Treatment 1 Intervention

Propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine

Group II: SOC propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam Active Control 1 Intervention

Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam.

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Henry M. Jackson Foundation for the Advancement of Military Medicine

Lead Sponsor

Trials

103

Recruited

94,300+

Uniformed Services University of the Health Sciences

Collaborator

Trials

130

Recruited

91,100+

Brooke Army Medical Center

Collaborator

Trials

134

Recruited

28,100+

Published Research Related to This Trial

The combination of ketamine and propofol, known as 'ketofol', was used in 42 women for short procedures and showed no significant adverse effects on blood pressure or heart rate, indicating it is safe for use in fit patients.

Patients experienced a favorable recovery from anesthesia with low rates of nausea and minimal emergence delirium, although 43% required airway support, highlighting the need for monitoring during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An audit of the haemodynamic and emergence characteristics of single-shot 'ketofol'. Grace, RF., Tang, DW., Namel, E.[2019]

In a study of 45 patients undergoing lung surgery, pretreatment with 1.0 mg/kg of ketamine completely eliminated pain from propofol injection during anesthesia induction, while 0.5 mg/kg reduced pain incidence and intensity.

Despite ketamine increasing secretion production, it did not significantly affect hemodynamics or oxygenation during one-lung ventilation, indicating its potential safety for use in lung surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine eliminates propofol pain but does not affect hemodynamics during induction with double-lumen tubes. Iwata, M., Inoue, S., Kawaguchi, M., et al.[2021]

In a study of 32 pediatric burn patients undergoing dressing changes, both propofol-ketamine and propofol-fentanyl combinations provided effective sedation and analgesia, with no significant differences in vital signs or sedation scores between the two groups.

However, the propofol-ketamine combination was found to be superior, as it resulted in significantly less restlessness during the procedure compared to the propofol-fentanyl combination, indicating a more stable sedation experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propofol-ketamine vs propofol-fentanyl combinations for deep sedation and analgesia in pediatric patients undergoing burn dressing changes. Tosun, Z., Esmaoglu, A., Coruh, A.[2022]

In a study involving 9 children with refractory convulsive status epilepticus (RSE), intravenous ketamine was found to be effective in resolving RSE in 6 of the patients, demonstrating its potential as a treatment option.

The treatment was deemed safe, as none of the patients experienced serious adverse events, suggesting that ketamine could be a viable alternative for children who do not respond to conventional anesthetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ketamine in refractory status epilepticus in children. Rosati, A., L'Erario, M., Ilvento, L., et al.[2022]

In a study of 50 patients with moderate to severe traumatic brain injury (TBI), ketofol (a mixture of propofol and ketamine) provided better hemodynamic stability during surgery compared to propofol, with fewer patients experiencing significant drops in mean arterial pressure (MAP).

Patients receiving ketofol required fewer vasopressors to maintain blood pressure, and while both groups had similar brain relaxation scores and outcomes at 30 and 90 days, the ketofol group showed lower levels of a serum biomarker associated with brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketofol as an Anesthetic Agent in Patients With Isolated Moderate to Severe Traumatic Brain Injury: A Prospective, Randomized Double-blind Controlled Trial. Maheswari, N., Panda, NB., Mahajan, S., et al.[2023]

In a study of 200 children undergoing laparoscopic surgery, the combination of ketamine and propofol (ketofol) significantly reduced extubating time (240 seconds vs. 530 seconds) compared to propofol alone, indicating faster recovery from anesthesia.

The ketofol group also experienced shorter overall duration of anesthesia (47 minutes vs. 60 minutes) and reduced length of stay in the post-anesthesia care unit (35 minutes vs. 100 minutes), while requiring lower doses of fentanyl and propofol, suggesting improved safety and efficacy in pediatric anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects on Recovery of Pediatric Patients Undergoing Total Intravenous Anesthesia with Propofol versus Ketofol for Short-Lasting Laparoscopic Procedures. Biliškov, AN., Ivančev, B., Pogorelić, Z.[2021]

Ketamine can be safely used in patients with neurological impairments when administered under controlled conditions, as it does not increase intracranial pressure and may improve cerebral perfusion.

In addition to its safety profile, ketamine shows neuroprotective effects in laboratory settings, suggesting potential benefits for brain injury recovery, although caution is needed due to possible neurotoxic effects at high doses in certain animal studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revising a dogma: ketamine for patients with neurological injury? Himmelseher, S., Durieux, ME.[2022]

In a study of 40 patients undergoing surgery for intracranial aneurysms, the use of ketofol (a mix of ketamine and propofol) resulted in better cerebral oxygenation compared to propofol alone, as indicated by higher jugular venous oxygen saturation (SjVO2) values at multiple time points during and after surgery.

Patients receiving ketofol experienced greater hemodynamic stability, with significantly fewer instances of hypotension and a lower need for rescue medications compared to those receiving propofol, suggesting that ketofol may be a safer option for maintaining anesthesia in neurosurgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Combination of Ketamine and Propofol (Ketofol) on Cerebral Oxygenation in Neurosurgical Patients: A Randomized Double-Blinded Controlled Trial. Bhaire, VS., Panda, N., Luthra, A., et al.[2022]

In a study of 271 adults undergoing deep sedation, the frequency of airway and respiratory adverse events requiring intervention was similar across groups receiving propofol alone and two different mixtures of propofol and ketamine (1:1 and 4:1).

No serious adverse events occurred in any group, indicating that all sedation methods were safe, although the 1:1 ketofol mixture was associated with higher recovery agitation compared to the other groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blinded, clinical trial of propofol, 1:1 propofol/ketamine, and 4:1 propofol/ketamine for deep procedural sedation in the emergency department. Miner, JR., Moore, JC., Austad, EJ., et al.[2022]

In a study using rat models of traumatic brain injury caused by maxillofacial impact, ketamine treatment significantly improved recovery time, with treated rats recovering about 2 days faster than the control group.

The results suggest that ketamine may be an effective intervention for enhancing recovery following traumatic brain injuries, indicating its potential therapeutic role in similar human injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Animal experiment of the ketamine effects on traumatic brain injury resulting from impact maxillofacial injury]. Zhang, C., Li, H., Liao, W., et al.[2013]

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In this study the effects of ketamine as an adjunct to an standard sedation regime in adult TBI patients will be investigated on the therapy intensity level and ...