Dataset Information

Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial.

ABSTRACT: BACKGROUND:Approximately 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. OBJECTIVE:This 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. METHODS:This 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. RESULTS:As 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. CONCLUSIONS:If 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 REGISTRATION:ClinicalTrials.gov NCT03146806; https://clinicaltrials.gov/ct2/show/NCT03146806. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/12125.

SUBMITTER: Shteamer JW

PROVIDER: S-EPMC6658277 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial.

Shteamer Jack W JW Harvey R Donald RD Spektor Boris B Curseen Kimberly K Egan Katherine K Chen Zhengjia Z Gillespie Theresa W TW Sniecinski Roman M RM Singh Vinita V

JMIR research protocols 20190430 4

<h4>Background</h4>Approximately 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 ...[more]

PMID: 31038469

Similar Datasets

Project description:INTRODUCTION:Pediatric sickle cell disease, highly prevalent in sub-Saharan Africa, carries great morbidity and mortality risk. Limited resources and monitoring make management of acute vaso-occlusive crises challenging. This study aims to evaluate the efficacy and safety of subdissociative intranasal ketamine as a cheap, readily available and easily administered adjunct to standard pain therapy. We hypothesise that subdissociative, intranasal ketamine may significantly augment current approaches to pain management in resource-limited settings in a safe and cost-effective manner. METHODS AND ANALYSIS:This is a multicentred, randomised, double-blind, placebo-controlled trial enrolling children 4-16 years of age with sickle cell disease and painful vaso-occlusive pain crises. Study sites include two sub-Saharan teaching and referral hospitals with acute intake areas. All patients receive standard analgesic therapy during evaluation. Patients randomised to the treatment arm receive 1 mg/kg intranasal ketamine at onset of therapy, while placebo arm participants receive volume-matched intranasal normal saline. All participants and clinical staff are blinded to the treatment allocation. Data will be analysed on an intention-to-treat basis. Primary endpoints are changes in self-report pain scales (Faces Pain Scale-Revised) at 30, 60 and 120 minutes and rates of adverse events. Secondary endpoints include hospital length of stay, total analgesia use and quality of life assessment 2-3 weeks postintervention. ETHICS AND DISSEMINATION:The research methods for this study have been approved by the Cameroon Baptist Convention Health Board Institutional Review Board (IRB2015-07), the Tanzanian National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/2299), Muhimbili National Hospital IRB (MNH/IRB/I/2015/14) and the Tanzanian Food and Drugs Authority (TFDA0015/CTR/0015/9). Data reports will be provided to the Data and Safety Monitoring Board (DSMB) periodically throughout the study as well as all reports of adverse events. All protocol amendments will also be reviewed by the DSMB. Study results, regardless of direction or amplitude, will be submitted for publication in relevant peer-reviewed journals. TRIAL REGISTRATION:ClinicalTrials.Gov, NCT02573714. Date of registration: 8 October 2015. Pre-results.

Project description:Importance:Timely 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. Objective:To determine whether intranasal ketamine is noninferior to intranasal fentanyl for pain reduction in children presenting with acute extremity injuries. Design, Setting, and Participants:The 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. Interventions:Intranasal ketamine (1.5 mg/kg) or intranasal fentanyl (2 µg/kg). Main Outcomes and Measures:The primary outcome was reduction in visual analog scale pain score 30 minutes after intervention. The noninferiority margin for this outcome was 10. Results:Of 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 Relevance:Ketamine 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 Registration:ClinicalTrials.gov Identifier: NCT02778880.

Project description:BackgroundUncooperative children may need to receive dental treatment under sedation, which is indicated when nonpharmacological behavior guidance is unsuccessful. There are randomized controlled trials (RCTs) comparing different sedative protocols for dental procedures; however, the evidence for superiority of one form over another is weak. The primary aim of this study is to investigate the efficacy of intranasally administered ketamine plus midazolam for the dental treatment of children.MethodsWe have designed a three-armed, parallel RCT to assess intranasal sedation using ketamine/midazolam in terms of the following measures: efficacy, safety, and cost-effectiveness. Two- to 6-year-old healthy children, referred for dental treatment in a dental sedation center in Brazil due to uncooperative behavior and requiring restorative dental procedures, will be recruited. Each child will be randomly assigned to one of the three groups: A - Intranasal administration of ketamine (4.0 mg/kg, maximum 100 mg) and midazolam (0.2 mg/kg, maximum 5.0 mg); B - Oral administration of ketamine (4.0 mg/kg, maximum 100 mg) and midazolam (0.5 mg/kg, maximum 20 mg); and C - Oral administration of midazolam (1.0 mg/kg, maximum 20 mg). The primary outcome is the child's behavior assessed through an observational scale using digital videos of the restorative dental treatment under sedation. The secondary outcomes are as follows: acceptance of sedative administration; memory of intraoperative events; the child's stress; adverse events; the child's pain during the procedure; the parent's, dentists', and child's perceptions of sedation; and economic analysis. Measures will be taken at baseline and drug administration and during and after the dental procedure. The necessary sample size was estimated to be 84 children after a blinded interim analysis of the first 30 cases.DiscussionThis study will provide data that can substantially add to science and pediatric dentistry as it examines the effect of sedative regimes from different perspectives (outcomes).Trial registrationClinicalTrials.gov, identifier: NCT02447289 . Registered on 11 May 2015, named "Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment (NASO)."

Dataset Information

Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial.

Publications

Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets