Low-Dose Ketamine for Burns
(IMPROVE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of Tennessee
Disqualifiers: Pregnant, Incarcerated, Under 18, others
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?The current standard of care (SOC) (i.e. fentanyl and midazolam) offers limited efficacy for preventing or relieving pain. Ketamine infusions may provide the benefits of analgesia, minimize adverse events, and reduce opioid use. The purpose of this study is to determine if adding a low dose ketamine infusion during wound care will safely provide pain relief for patients with burn injury.
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.
Is low-dose ketamine generally safe for humans?
Research on ketamine, often used for depression, shows it can have temporary side effects like changes in mood or heart rate, but these are usually short-lived. There are rare reports of serious issues like breathing problems, so careful monitoring is recommended during treatment.
12345How does low-dose ketamine differ from other treatments for burns?
Low-dose ketamine is unique for burn treatment because it can provide pain relief through different routes, such as intravenous or potentially oral and sublingual, which are being explored for other pain conditions. Its rapid action and potential for fewer side effects compared to traditional pain medications make it a novel option for managing burn pain.
36789Eligibility Criteria
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
Unable to report NRS
I am under 18 years old.
+4 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: KetamineExperimental Treatment1 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: PlaceboPlacebo Group1 Intervention
0.9% saline to begin 1 hour before wound care, continuing through and for 1 hour following wound care.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Regional One HealthMemphis, TN
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Who Is Running the Clinical Trial?
University of TennesseeLead Sponsor
References
Side-effects associated with ketamine use in depression: a systematic review. [2019]This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depresssion. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users. We recommend large-scale clinical trials that include multiple doses of ketamine and long-term follow up to assess the safety of long-term regular use.
A comparison of the pharmacokinetics and NMDAR antagonism-associated neurotoxicity of ketamine, (2R,6R)-hydroxynorketamine and MK-801. [2022]With the increasing use of ketamine as an off-label treatment for depression and the recent FDA approval of (S)-ketamine for treatment-resistant depression, there is an increased need to understand the long-term safety profile of chronic ketamine administration. Of particular concern is the neurotoxicity previously observed in rat models following acute exposure to high doses of ketamine, broadly referred to as 'Olney's lesions'. This type of toxicity presents as abnormal neuronal cellular vacuolization, followed by neuronal death and has been associated with ketamine's inhibition of the N-methyl-d-aspartate receptor (NMDAR). In this study, a pharmacological and neuropathological analysis of ketamine, the potent NMDAR antagonist MK-801, and the ketamine metabolite (2R,6R)-hydroxynorketamine [(2R,6R)-HNK)] in rats is described following both single dose and repeat dose drug exposures. Ketamine dosing was studied up to 20 mg/kg intravenously for the single-dose neuropathology study and up to 60 mg/kg intraperitoneally for the multiple-dose neuropathology study. MK-801 dosing was studied up to 0.8 mg/kg subcutaneously for both the single and multiple-dose neuropathology studies, while (2R,6R)-HNK dosing was studied up to 160 mg/kg intravenously in both studies. These studies confirm dose-dependent induction of 'Olney's lesions' following both single dose and repeat dosing of MK-801. Ketamine exposure, while showing common behavioral effects, did not induce wide-spread Olney's lesions. Treatment with (2R,6R)-HNK did not produce behavioral effects, toxicity or any evidence of Olney's lesion formation. Based on these results, future NMDAR-antagonist neurotoxicity studies should strongly consider taking pharmacokinetics more thoroughly into account.
Subcutaneous Ketamine in Depression: A Systematic Review. [2021]Background: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability. Methods: A systematic literature search was carried out, from inception through March, 2021, using PubMed/MEDLINE, EMBASE and Web of Science, with no limits of language. After identifying 159 potentially relevant articles, 12 articles were selected after applying our inclusion/exclusion criteria. These comprised two randomized clinical trials, five case-reports and five retrospective studies. Given the small number of studies found and their heterogeneous nature, a meta-analysis was not considered appropriate. Here we provide a synthesis of these data including participant characteristics, dose range, efficacy, safety/ tolerability. Risk of bias was accessed using the Cochrane risk of bias tool. Results: SC Ketamine was administered to unipolar and bipolar patients a single or multiple doses, weekly or twice-weekly, a dose-titration approach was made in major studies, dose ranged from 0.1 to 0.5 mg/Kg of racemic ketamine and 0.5-1 mg/Kg of esketamine. Across all studies, SC ketamine showed a rapid and robust antidepressant effect, with response/ remission rates from 50 to 100% following both single or multiple doses, with transitory side effects. Conclusion: SC racemic ketamine and esketamine in depression is a promising strategy showing beneficial efficacy and tolerability. Future studies exploring the SC route, its cost-effectiveness, and a direct comparison with IV and intranasal (IN) protocols are warranted. Systematic Review Registration: CRD42019137434.
Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. [2021]Ketamine's pharmacological profile makes it an interesting and useful drug to challenge treatment-resistant-depression (TRD). Emerging adverse events associated with single-slow-sub-anaesthetic doses for the treatment of depression are common, although generally transient and self-limited. Nevertheless, data on the safety of this practice are scarce. Thus, it seems timely before ketamine is used for clinical treatment of depression to recommend careful monitoring and reporting of all potential adverse events related to ketamine administration. Here, we describe a case of apnea during slow sub-anaesthetic infusion of intravenous ketamine for the treatment of resistant depression. As far as we are concerned, this is an uncommon, previously unreported, and potentially severe adverse event that clinicians should be aware of, and specific management measures should be implemented.
The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]On a background of the rapidly expanding clinical use of ketamine and esketamine for treatment of depression and other conditions, we examined safety monitoring, seeking to identify knowledge gaps relevant to clinical practice.
Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: Preliminary findings from a three-way randomized, crossover study. [2021]Enterally administered low-dose ketamine is being used increasingly to treat pain states. However, suitable oral or sublingual formulations are not available. The objective of the study was to develop a lozenge formulation of ketamine for use in patients with neuropathic pain, and to investigate its storage stability and bioavailability after oral or sublingual administration.
Thiamylal Plus Pentazocine Shows Similar Efficacy as Ketamine Plus Midazolam for Painful Procedures in Children With Leukemia. [2019]This retrospective study compared the use of thiamylal plus pentazocine (TP) to ketamine plus midazolam (KM) in children with leukemia who were undergoing bone marrow aspiration and/or intrathecal chemotherapy. A total of 268 procedures in 35 children with leukemia were retrospectively analyzed for efficacy and adverse events. All procedures were successfully completed without severe adverse events. TP induced significantly faster sedation. The incidents of desaturation were significantly greater in the TP group, but were transient and recovered by oxygen supplementation alone. Therefore, TP can be a useful combination with a similar efficacy as KM for painful procedures in children.
[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. [2013]To evaluate the efficacy of low dose ketamine (0.15 mg/Kg i.v.) as a pre-emptive pain relief after general anesthesia.
Population pharmacokinetics of S-ketamine and norketamine in healthy volunteers after intravenous and oral dosing. [2018]Low-dose ketamine is a lucrative therapeutic approach in cancer pain, perioperative treatment of pain, and management of treatment-resistant depression. The analgesic potency of its main metabolite norketamine is thought to be one third that of ketamine. However, few studies exist on the pharmacokinetics of orally administered S-ketamine.