Dataset Information

A dose-escalation clinical trial of intranasal ketamine for uncontrolled cancer-related pain.

ABSTRACT:

Study objective

The objective of our study was to determine safety and pharmacology (pharmacokinetics and preliminary efficacy) of intranasal (IN) ketamine for uncontrolled cancer-related pain.

Design

Dose escalation clinical trial.

Setting

Outpatient.

Patients

Ten adult patients with uncontrolled cancer-related pain.

Intervention

Each patient received escalating doses of ketamine over four visits, each 2-5 days apart: 10 mg IN at visit 1, 10 mg intravenous (IV) at visit 2, 30 mg IN at visit 3, and 50 mg IN at visit 4.

Measurements

Pain was measured before and after drug administration for up to 4 h using the 11 point (0-10) Numerical Pain Rating Scale (NPRS).

Main results

All subjects had advanced cancer, with intractable pain, despite being on moderate dosage of opioids. There was a statistically significant reduction in median NPRS by 1.5 (1-4), 3 (2-3), and 4 (3-5) points at 60 min after receiving the medication and remained decreased by 1.5 (1-2), 2 (1-2) and 1 (1-4) points at the end of the study visit (240 min) with the 10 mg, 30 mg and 50 mg IN dosage, respectively. The median percentage of maximal pain relief being 22.5 (16.6-71.5), 65.5 (40-100), and 69.25 (50-100) for 10 mg, 30 mg and 50 mg IN dosage, respectively and 100 (75-100) with 10 mg IV dose. All side effects (nausea and feeling of unreality) resolved by the end of each study visit. No severe adverse events occurred.

Conclusion

In this single-institution study, all dosages of IN ketamine administered in the study (10, 30, and 50 mg) provided significant pain relief for intractable cancer-related pain and were well tolerated. The 50 mg dose provided maximal pain relief without major side effects. Further study focused on repeated administration efficacy and safety for cancer-related pain is warranted.

SUBMITTER: Singh V

PROVIDER: S-EPMC9118341 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

A dose-escalation clinical trial of intranasal ketamine for uncontrolled cancer-related pain.

Singh Vinita V Gillespie Theresa W TW Lane Olabisi O Spektor Boris B Zarrabi Ali John AJ Egan Katherine K Curseen Kimberly K Tsvetkova Maya M Beumer Jan H JH Sniecinski Roman R Shteamer Jack W JW Switchenko Jeffery J Harvey R Donald RD

Pharmacotherapy 20220221 4

<h4>Study objective</h4>The objective of our study was to determine safety and pharmacology (pharmacokinetics and preliminary efficacy) of intranasal (IN) ketamine for uncontrolled cancer-related pain.<h4>Design</h4>Dose escalation clinical trial.<h4>Setting</h4>Outpatient.<h4>Patients</h4>Ten adult patients with uncontrolled cancer-related pain.<h4>Intervention</h4>Each patient received escalating doses of ketamine over four visits, each 2-5 days apart: 10 mg IN at visit 1, 10 mg intravenous (I ...[more]

PMID: 35146776

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Project description:BackgroundApproximately 12 million Americans are affected with cancer. Of these, 53% experience pain at all stages of cancer. Pain may remain uncontrolled despite high-dose opioid therapy, and opioids have many well-documented harmful side effects. Intranasal ketamine has been shown to be effective in controlling breakthrough noncancer pain in a double-blind randomized control trial (DBRCT) by Carr et al in 2003 as well as to help with depression in a DBRCT by Lapidus et al in 2014. We seek to obtain preliminary data on the safety, feasibility, and utility of this novel technique for the treatment of uncontrolled cancer pain.ObjectiveThis study aimed to obtain preliminary data via a clinical trial addressing the safety, feasibility, pharmacokinetics, and pharmacodynamics of intranasal ketamine. These initial findings will be applied to a subsequent trial to determine the effectiveness and associated toxicities of ketamine in a larger sample of cancer patients and to address the compelling need to identify new, successful management therapies for cancer pain.MethodsThis is an institutional review board- and investigational new drug-approved, prospective phase I/II trial to investigate the safety and use of intranasal ketamine in patients with uncontrolled pain related to cancer or cancer treatment. Informed consent will be obtained prior to all study procedures. All patients will be assigned to the same investigational treatment arm. After patient selection via inclusion/exclusion criteria, patients will be seen over 5 visits, with each visit conducted 2-7 days apart. Patients will be administered ketamine on visits 1-4 and monitored for 240 minutes with continuous pulse oximetry and regular blood pressure checks. Blood samples as well as patient-reported outcomes will be collected at set time points at baseline and after drug delivery. Patients will receive 10 mg intranasal ketamine on visit 1, 10 mg intravenous ketamine on visit 2, 30 mg intranasal ketamine on visit 3, and 50 mg intranasal ketamine on visit 4. On visit 5, an addition blood sample will be drawn.ResultsAs of March 2019, enrollment is in progress, and a total of 7 subjects have completed the study. Enrollment is expected to be completed by April 2019. Final data analysis will commence soon after, and the results are expected to be submitted for publication in 2019.ConclusionsIf intranasal ketamine can be utilized for pain control in cancer patients, it could provide superior analgesia and better quality of life, without the risk of significant respiratory depression and constipation associated with opioid medications. These findings will be an important initial step toward testing the effectiveness of intranasal ketamine as a nonopioid medication for cancer pain and as potential maintenance outpatient therapy.Trial registrationClinicalTrials.gov NCT03146806; https://clinicaltrials.gov/ct2/show/NCT03146806.International registered report identifier (irrid)DERR1-10.2196/12125.

Project description:ImportanceTimely analgesia is critical for children with injuries presenting to the emergency department, yet pain control efforts are often inadequate. Intranasal administration of pain medications provides rapid analgesia with minimal discomfort. Opioids are historically used for significant pain from traumatic injuries but have concerning adverse effects. Intranasal ketamine may provide an effective alternative.ObjectiveTo determine whether intranasal ketamine is noninferior to intranasal fentanyl for pain reduction in children presenting with acute extremity injuries.Design, setting, and participantsThe Pain Reduction With Intranasal Medications for Extremity Injuries (PRIME) trial was a double-blind, randomized, active-control, noninferiority trial in a pediatric, tertiary, level 1 trauma center. Participants were children aged 8 to 17 years presenting to the emergency department with moderate to severe pain due to traumatic limb injuries between March 2016 and February 2017. Analyses were intention to treat and began in May 2017.InterventionsIntranasal ketamine (1.5 mg/kg) or intranasal fentanyl (2 µg/kg).Main outcomes and measuresThe primary outcome was reduction in visual analog scale pain score 30 minutes after intervention. The noninferiority margin for this outcome was 10.ResultsOf 90 children enrolled, 45 (50%) were allocated to ketamine (mean [SD] age, 11.8 [2.6] years; 26 boys [59%]) and 45 (50%) to fentanyl (mean [SD] age, 12.2 [2.3] years; 31 boys [74%]). Thirty minutes after medication, the mean visual analog scale reduction was 30.6 mm (95% CI, 25.4-35.8) for ketamine and 31.9 mm (95% CI, 26.6-37.2) for fentanyl. Ketamine was noninferior to fentanyl for pain reduction based on a 1-sided test of group difference less than the noninferiority margin, as the CIs crossed 0 but did not cross the prespecified noninferiority margin (difference in mean pain reduction between groups, 1.3; 90% CI, -6.2 to 8.7). The risk of adverse events was higher in the ketamine group (relative risk, 2.5; 95% CI, 1.5-4.0), but all events were minor and transient. Rescue analgesia was similar between groups (relative risk, 0.89; 95% CI, 0.5-1.6).Conclusions and relevanceKetamine provides effective analgesia that is noninferior to fentanyl, although participants who received ketamine had an increase in adverse events that were minor and transient. Intranasal ketamine may be an appropriate alternative to intranasal fentanyl for pain associated with acute extremity injuries. Ketamine should be considered for pediatric pain management in the emergency setting, especially when opioids are associated with increased risk.Trial registrationClinicalTrials.gov Identifier: NCT02778880.

Project description:ObjectiveTo date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions.MethodsWe compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in CP patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, one day and seven days after the infusion. A planned sample size of 40 patients randomly assigned to treatment order was estimated to provide 80% power to detect a hypothesized treatment difference after the infusion.Main Outcome and Measures: The primary outcome measures were change in PTSD symptom severity assessed with the Impact of Event Scale-Revised (IES-R) and Visual Analogue Scale (VAS) for pain administered by a study clinician 24 hours post infusion. Secondary outcome measures included Impact of Event Scale-Revised (IES-R), VAS and Brief Pain Inventory (Short Form) for pain 1 week after the infusion.ResultsBoth treatments offered comparable improvement of PTSD and CP symptoms that persisted for 7 days after the infusion. Patients with comorbid PTSD and CP experienced less dissociative side effects compared to the CP group. Surprisingly, ketorolac infusion resulted in dissociative symptoms in CP patients only.ConclusionsThis first prospective study comparing effects of subanesthetic ketamine versus ketorolac infusions for comorbid PTSD and CP, suggests that both ketamine and ketorolac might offer meaningful and durable response for both PTSD and CP symptoms.

Project description:Background and objectivesPerioperative ketamine has been shown to reduce opioid consumption and pain after surgery. Ketamine is most often given as an infusion, but an alternative is single-dose ketamine. Single-dose ketamine at up to 1 mg/kg has been shown to reduce symptoms of depression, and a wide range of dosages has been used for pain in the emergency department. However, limited data exists on the tolerability and efficacy of a single-dose of ketamine at 0.6 mg/kg for pain when administered immediately after surgery. We conducted a pilot study of single-dose ketamine in patients undergoing mastectomy with reconstruction, hypothesizing that a single-dose of ketamine is well tolerated and can relieve postoperative pain and improve mood and recovery.MethodsThis is a randomized, single-blind, placebo-controlled, two-arm parallel, single-center study. Thirty adult women undergoing mastectomy with reconstruction for oncologic indication received a single-dose of ketamine (0.6mg/kg) or placebo after surgery in the post-anesthesia care unit (PACU). Patients were followed through postoperative day (POD) 7. The primary outcome was postoperative pain measured by the Brief Pain Inventory (BPI) pain subscale on POD 1 and 2. Secondary outcomes include effects on opioid use, PROMIS fatigue and sleep, mood, Quality of Recovery-15, and the Breast Cancer Pain Questionnaire.ResultsSide effects were minor and not significantly different in frequency between groups. The ketamine group reported lower scores on the BPI pain severity subscale, especially at POD 7; however, the difference was not statistically significant. There were no statistically significant differences between ketamine and placebo groups for the secondary outcomes.ConclusionA single-dose of ketamine at 0.6mg/kg administered postoperatively in the PACU is well tolerated in women undergoing mastectomy and may confer better pain control up to one week after surgery. Future studies with larger sample sizes are necessary to adequately characterize the effect of postoperative single-dose ketamine on pain control in this population.

Dataset Information

A dose-escalation clinical trial of intranasal ketamine for uncontrolled cancer-related pain.

Study objective

Design

Setting

Patients

Intervention

Measurements

Main results

Conclusion

Publications

A dose-escalation clinical trial of intranasal ketamine for uncontrolled cancer-related pain.

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