Low-Dose Ketamine for Burns

(IMPROVE Trial)

Overseen By David M Hill, Pharm.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Tennessee

Disqualifiers: Pregnant, Incarcerated, Under 18, others

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: Unknown

Duration: 7 days

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a low dose of ketamine, an anesthetic, can relieve pain during wound care for burn patients. Current treatments such as fentanyl and midazolam are not always effective, so researchers aim to determine if ketamine provides better pain relief with fewer side effects. Participants will receive either a ketamine infusion or a placebo (a substance with no active drug) before and during wound care. The study seeks individuals admitted with burn injuries. As a Phase 4 trial, this research involves an FDA-approved treatment to explore how ketamine can benefit more patients.

Do I need to stop my current medications to join the trial?

The trial information does not specify if 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?

Research has shown that ketamine often helps manage pain in people with burns. Studies have found that a low dose of ketamine can effectively relieve pain during wound care, reducing the need for opioids like fentanyl.

However, some safety concerns exist. One study found that ketamine use in burn patients could cause liver problems, with the risk depending on the dose and duration of use. Despite these concerns, ketamine remains widely used in burn care because it controls pain effectively without the heavy side effects of opioids.

Overall, while ketamine is generally safe at low doses, some risks exist. Participants should discuss these with their doctors before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for burn pain rely on opioids, which can have significant side effects and risk of addiction. But ketamine offers a different approach. Unlike opioids, ketamine operates by blocking NMDA receptors in the brain, which can help manage pain without the same risk of dependency. Researchers are excited because ketamine's rapid action might provide quicker pain relief during wound care, potentially improving patient comfort and recovery times.

What evidence suggests that low-dose ketamine might be an effective treatment for burn pain?

Studies have shown that ketamine can effectively manage pain from burn injuries. Research indicates that ketamine administered through an IV reduces pain sensitivity more effectively than opioids, the usual pain medications. In this trial, some participants will receive a low-dose ketamine infusion, which previous studies found to work as well as morphine during dressing changes, with more predictable effects. Another study noted that ketamine use could reduce the amount of opioids needed during burn wound care. Overall, these findings suggest that ketamine offers a promising option for pain relief in burn patients. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with burn injuries who experience pain during wound care. It aims to see if low-dose ketamine can help manage their pain better than the current standard treatments without increasing opioid use.

Inclusion Criteria

I was admitted for a burn injury.

Exclusion Criteria

Unable or unwilling to consent within 72 hours

Pregnant

Incarcerated

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either ketamine infusion or placebo during wound care procedures

7 days

Daily visits for wound care

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview The study tests whether a low dose of ketamine, given as an infusion alongside the usual care (like fentanyl and midazolam), can provide better pain relief during burn wound care compared to just using the standard medications alone.

How Is the Trial Designed?

Group I: Ketamine Experimental Treatment 1 Intervention

Ketamine infusion (0.3 mg/kg/hr) to begin 1 hour before wound care, continuing through and for 1 hour following wound care.

Group II: Placebo Placebo Group 1 Intervention

0.9% saline to begin 1 hour before wound care, continuing through and for 1 hour following wound care.

Who Is Running the Clinical Trial?

University of Tennessee

Lead Sponsor

Trials

202

Recruited

146,000+

Published Research Related to This Trial

A new lozenge formulation of ketamine, containing 25 mg, demonstrated good chemical stability for at least 14 weeks, making it a viable option for pain management.

The bioavailability of the lozenge was found to be 24% for both oral and sublingual administration, indicating it could effectively deliver ketamine for treating chronic neuropathic pain, although further efficacy studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: Preliminary findings from a three-way randomized, crossover study. Chong, C., Schug, SA., Page-Sharp, M., et al.[2021]

In a study of 268 procedures involving 35 children with leukemia, the combination of thiamylal plus pentazocine (TP) provided faster sedation compared to ketamine plus midazolam (KM) during bone marrow aspirations and intrathecal chemotherapy.

While TP was associated with a higher incidence of transient desaturation events, these were manageable with oxygen supplementation, indicating that TP can be a safe and effective alternative for sedation in pediatric oncology procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiamylal Plus Pentazocine Shows Similar Efficacy as Ketamine Plus Midazolam for Painful Procedures in Children With Leukemia. Nakagawa, S., Okamoto, Y., Kodama, Y., et al.[2019]

In a study of 69 gynecological surgery patients, low dose ketamine (0.15 mg/Kg) administered preoperatively did not provide a preemptive analgesic effect, as indicated by similar pain scores at rest compared to placebo.

However, patients receiving ketamine postoperatively experienced less pain upon movement on the fifth day and required less morphine in the first 6 hours, suggesting that while preemptive use is ineffective, postoperative ketamine can still improve pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. Gilabert Morell, A., Sánchez Pérez, C.[2013]

In a study involving 11 healthy volunteers, oral S-ketamine showed low bioavailability (8%) and high clearance, indicating that while it is absorbed poorly, it is rapidly eliminated from the body.

The study suggests that small oral doses of S-ketamine could effectively provide analgesic effects through its metabolite norketamine, making it a potential alternative to frequent intravenous dosing for managing chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of S-ketamine and norketamine in healthy volunteers after intravenous and oral dosing. Fanta, S., Kinnunen, M., Backman, JT., et al.[2018]

This systematic review analyzed 60 studies on the safety of ketamine for treating depression, revealing that acute doses of ketamine led to more frequent side effects, including psychiatric and cardiovascular issues, compared to placebo.

There is a notable lack of data on the long-term safety and effects of repeated ketamine dosing, highlighting the need for large-scale clinical trials to better understand its safety profile over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. Short, B., Fong, J., Galvez, V., et al.[2019]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., et al.[2023]

Chronic administration of ketamine does not induce widespread neurotoxicity ('Olney's lesions') in rats, unlike the NMDAR antagonist MK-801, which showed dose-dependent lesions with both single and repeat dosing.

The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) was found to be safe, as it did not cause any behavioral effects or neurotoxic lesions, suggesting it may be a safer alternative for treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the pharmacokinetics and NMDAR antagonism-associated neurotoxicity of ketamine, (2R,6R)-hydroxynorketamine and MK-801. Morris, PJ., Burke, RD., Sharma, AK., et al.[2022]

Ketamine shows promise as a treatment for treatment-resistant depression (TRD), but its use can lead to common adverse events, which are usually temporary.

A case of apnea during a slow sub-anesthetic infusion of ketamine highlights a rare but serious potential side effect, emphasizing the need for careful monitoring and management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. Gómez-Revuelta, M., Fernández-Rodríguez, M., Boada-Antón, L., et al.[2021]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK85859/

A systematic review of ketamine as an analgesic agent in ... Intravenous ketamine showed some efficacy as an analgesic for burn injuries, with a reduction in secondary hyperalgesia when compared with opioid analgesia ...

2. academic.oup.com academic.oup.com/painmedicine/article/12/10/1551/1890882

Systematic Review of Ketamine as an Analgesic Agent in ... Intravenous ketamine showed some efficacy as an analgesic for burn injuries, with a reduction in secondary hyperalgesia when compared with opioid analgesia ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03095222

Exploring the Safety and Efficacy of Low-dose Ketamine ... The purpose of this study is to identify the optimal dosing strategy for low-dose ketamine infusions in adult acute burn injury patients when used with usual ...

4. anesthesioljournal.com anesthesioljournal.com/articles/effectiveness-intravenous-low-dose-ketamine-versus-morphine-procedural-burn-pain-management-dressing-changes-randomized-clinical-trial.html

Effectiveness of Intravenous Low-Dose Ketamine Versus ... This study suggests that low-dose ketamine provides as effective and more predictable procedural analgesia as morphine during dressing procedures for adult ...

5. mdpi.com mdpi.com/2077-0383/13/3/764

The Role of Ketamine as a Component of Multimodal ... The aims of this study are to examine the effect of ketamine administered during burn wound dressing on intraprocedural opioid consumption, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3127303/

Comparison of effects of ketamine ... In this study, we have demonstrated that three sedoanalgesic techniques provided effective sedation and analgesia during wound dressing changes in burn patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10832380/

Ketamine restriction correlates with reduced cholestatic ... In a cohort of 279 critically ill patients with burn injury, ketamine was associated with a risk of liver bile duct toxicity. The risk was found to be dependent ...

8. academic.oup.com academic.oup.com/painmedicine/article-pdf/12/10/1551/5342122/12-10-1551.pdf

A Systematic Review of Ketamine as an Analgesic Agent in ... Despite the sparse empirical data and evidence found in this review, ketamine is a widely used analgesic agent in burn patients across all stages of burn injury ...