Ketamine + Propofol for Traumatic Brain Injury

(Ketamine Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

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

Disqualifiers: Cardiovascular disease, Pregnancy, Prisoners, others

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This protocol is for an open-label randomized trial evaluating the safety of using ketamine in combination with propofol for sedation versus the standard of care analgosedation in patients admitted to the intensive care unit with severe traumatic brain injury.

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 data supports the effectiveness of the drug Ketamine + Propofol for Traumatic Brain Injury?

Research suggests that the combination of ketamine and propofol, known as ketofol, may improve brain blood flow and oxygen levels, which could be beneficial for patients with brain injuries. Additionally, ketamine has been shown to have protective effects on the brain, potentially making it a safe option for those with neurological injuries. ^{1 2 3 4 5}

Is the combination of ketamine and propofol safe for use in humans?

The combination of ketamine and propofol, known as ketofol, has been studied for safety in various settings. It generally shows minimal adverse effects on heart and blood pressure, but some patients may need help with breathing. In one study, 43% of patients required airway support, indicating a potential risk for breathing issues. ^{2 6 7 8 9}

How is the drug ketamine + propofol unique for treating traumatic brain injury?

The combination of ketamine and propofol, known as ketofol, is unique because it may improve cerebral oxygenation and reduce the need for additional opioids during treatment, which can be beneficial for patients with traumatic brain injury. This combination also minimizes adverse hemodynamic effects and provides favorable wake-up characteristics compared to other sedative options. ^{1 2 7 8 10}

Eligibility Criteria

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 am between 18 and 65 years old.

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.

Trial Timeline

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

Treatment Details

Interventions

• Ketamine (Other)

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.

Participant Groups

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, 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Brooke Army Medical Center Fort Sam Houston, TX

Who Is Running the Clinical Trial?

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

Uniformed Services University of the Health Sciences Collaborator

Brooke Army Medical Center Collaborator

References

1. United States 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. [2023] The effects of ketofol (propofol and ketamine admixture) on systemic hemodynamics and outcomes in patients undergoing emergency decompressive craniectomy for traumatic brain injury (TBI) are unknown and explored in this study.

2. India 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. [2022] The effects of ketofol (a combination of ketamine and propofol) on systemic hemodynamics and requirement of opioids/Propofol have already been studied and published. However, there is paucity in the literature on the effects of ketofol on cerebral oxygenation. This study aims to compare the effects of ketofol (ketamine + propofol [1:5]) with propofol on cerebral oxygenation using jugular venous oxygen saturation (SjVO2), in patients undergoing surgical clipping of intracranial aneurysms.

3. China pubmed.ncbi.nlm.nih.gov

[Animal experiment of the ketamine effects on traumatic brain injury resulting from impact maxillofacial injury]. [2013] To test the effects of ketamine (KET) on traumatic brain injury resulting from impact maxillofacial injury.

4. Switzerland pubmed.ncbi.nlm.nih.gov

Effects on Recovery of Pediatric Patients Undergoing Total Intravenous Anesthesia with Propofol versus Ketofol for Short-Lasting Laparoscopic Procedures. [2021] Combining ketamine and propofol (ketofol) was suggested as a new concept for sedation and general anesthesia in pediatric populations for various conditions. The aim of the present study was to determine the effect of total intravenous anesthesia (TIVA) with propofol and ketofol on recovery after laparoscopic surgery in pediatric patients.

5. United States pubmed.ncbi.nlm.nih.gov

Revising a dogma: ketamine for patients with neurological injury? [2022] We evaluated reports of randomized clinical trials in the perioperative and intensive care setting concerning ketamine's effects on the brain in patients with, or at risk for, neurological injury. We also reviewed other studies in humans on the drug's effects on the brain, and reports that examined ketamine in experimental brain injury. In the clinical setting, level II evidence indicates that ketamine does not increase intracranial pressure when used under conditions of controlled ventilation, coadministration of a gamma-aminobutyric acid (GABA) receptor agonist, and without nitrous oxide. Ketamine may thus safely be used in neurologically impaired patients. Compared with other anesthetics or sedatives, level II and III evidence indicates that hemodynamic stimulation induced by ketamine may improve cerebral perfusion; this could make the drug a preferred choice in sedative regimes after brain injury. In the laboratory, ketamine has neuroprotective, and S(+)-ketamine additional neuroregenerative effects, even when administered after onset of a cerebral insult. However, improved outcomes were only reported in studies with brief recovery observation intervals. In developing animals, and in certain brain areas of adult rats without cerebral injury, neurotoxic effects were noted after large-dose ketamine. These were prevented by coadministration of GABA receptor agonists.

6. United States 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. [2022] We compare the frequency of airway and respiratory adverse events leading to an intervention between propofol with 1:1 and 4:1 mixtures of propofol and ketamine (ketofol).

7. United States pubmed.ncbi.nlm.nih.gov

An audit of the haemodynamic and emergence characteristics of single-shot 'ketofol'. [2019] 'ketofol', the single-syringe combination of ketamine and propofol (50 mg of ketamine and 90 mg of propofol in a 10 ml syringe) is becoming increasingly popular for short procedures, progressively replacing the more traditional use of ketamine and diazepam in some settings. This audit examined the haemodynamic, emergence and other characteristics of ketofol administration in 42, otherwise fit, women undergoing bilateral post-partum tubal ligation at Vila Central Hospital in Vanuatu. The combination of ketamine and propofol had no clinically important adverse haemodynamic effects. Wake-up from ketofol was favourable, with low rates of nausea and minimal emergence delirium. However, 43% of patients required airway support. For short procedures such as post-partum tubal ligation in fit patients, ketofol appears to have minimal adverse haemodynamic effects and favourable emergence characteristics.

8. Japan pubmed.ncbi.nlm.nih.gov

Ketamine eliminates propofol pain but does not affect hemodynamics during induction with double-lumen tubes. [2021] Propofol injection during induction of anesthesia induces pain. Ketamine has been shown to reduce the injection pain. However, ketamine has unfavorable adverse effects, including increased secretion production and hemodynamic responses, which might induce pulmonary or hemodynamic adverse events, especially in patients undergoing lung surgery who require a double-lumen tube (DLT). The aim of this study was to determine whether ketamine can safely reduce propofol injection pain during induction of anesthesia for lung surgery.

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ketamine in refractory status epilepticus in children. [2022] To evaluate the efficacy and safety of ketamine (KE) in the management of refractory convulsive status epilepticus (RSE) in children.

10. France pubmed.ncbi.nlm.nih.gov

Propofol-ketamine vs propofol-fentanyl combinations for deep sedation and analgesia in pediatric patients undergoing burn dressing changes. [2022] The aim of this study was to compare propofol-ketamine (PK) and propofol-fentanyl (PF) combinations for deep sedation and analgesia in pediatric burn wound dressing changes.