Pediatric Ketamine Study for Pain Management

NCT ID: NCT02388321

Last Updated: 2018-05-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-01
• Study Completion Date: 2017-10-14

Brief Summary

Direct comparison of intranasal sub-dissociative dose ketamine with intranasal fentanyl for the treatment of moderate to severe pain in pediatric patients in the emergency department.

Detailed Description

Intranasal (IN) delivery of analgesic agents provides rapid and convenient drug administration without the need for needles. In children, the placement of an intravenous line often increases anxiety and pain, requires nursing time, and can be very difficult to achieve, so the IN route is particularly advantageous. IN delivery of fentanyl has become increasingly more common in pain management for children in many settings, including pre-hospital and emergency department (ED) settings. Over the past decade, many studies have demonstrated that intranasal fentanyl is as effective as intravenous morphine to treat acute moderate to severe pain. Intranasal fentanyl has become standard of care in some pediatric EDs with the advantage of avoiding intravenous line placement. However, adverse effects attributed to IN fentanyl are similar to those of other opioid analgesics: hypotension, sedation, and occasionally respiratory depression. Ketamine is a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist that blocks the release of the excitatory neurotransmitter glutamate and provides anesthesia, amnesia, and analgesia by decreasing central sensitization and "wind-up" phenomenon. Due to its high lipid solubility, ketamine rapidly crosses the blood-brain barrier, provides rapid onset of action (peak concentration at 1 minute after intravenous push) and rapid recovery to baseline (duration of action 5-15 minutes after intravenous push). At sub-dissociative doses, either used as an adjunct to opioid analgesics or as a solo agent, ketamine provides effective analgesia while preserving airway patency, ventilation, and cardiovascular stability.

Ketamine has been less studied for pain management, however it has been safely used via different routes of administration in children. Studies dating back to 1990's use ketamine at doses as high as 6 mg/kg intranasally in children for pre-medication prior to surgery or for sedation with little or no reported adverse effects. A hospital in Australia is currently conducting a clinical trial comparing IN fentanyl 1.5 ug/kg to IN ketamine 1mg/kg for the treatment of pain caused by isolated musculoskeletal injury. The intention of our study is similar to this, however the investigators will not limit the patients to those with only musculoskeletal pain and a more simplified pain scale will be used.

To assess pain, the investigators will use the standard pain scale that is currently used in our Pediatric ED in order to minimize the need to re-train any of our staff with a different pain scale. The scale incorporates the Numerical rating scale (0-10 scale; NRS) and the Wong-Baker faces pain scale (6 faces corresponding to 0,2,4,6,8,10; WBS). While prior studies have used different pain scales, primarily the visual analog scale (VAS), the scales that the investigator currently use have been validated in children in 2009.

Conditions

Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine

intranasal sub-dissociative dose ketamine for the treatment of moderate to severe pain in pediatric patients in the emergency department.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

intranasal sub-dissociative dose ketamine for the treatment of moderate to severe pain in pediatric patients in the emergency department.

Fentanyl

intranasal fentanyl for the treatment of moderate to severe pain in pediatric patients in the emergency department.

Group Type: ACTIVE_COMPARATOR

Fentanyl

Intervention Type: DRUG

intranasal fentanyl for the treatment of moderate to severe pain in pediatric patients in the emergency department.

Interventions

Ketamine

intranasal sub-dissociative dose ketamine for the treatment of moderate to severe pain in pediatric patients in the emergency department.

Intervention Type: DRUG

Fentanyl

intranasal fentanyl for the treatment of moderate to severe pain in pediatric patients in the emergency department.

Intervention Type: DRUG

Other Intervention Names

Fetanyl

Eligibility Criteria

Inclusion Criteria

• Children aged 3-17,
• weighing less than 50kg
• present to the pediatric ED with moderate-severe acute pain (defined as pain greater than or equal to 6/10).
• Treating physician determines the patient to require opioid analgesia.

Exclusion Criteria

• Children with facial trauma or any abnormal nasal anatomy;
• developmentally delayed children;
• children with head trauma/increased intracranial pressure (ICP);
• children with known allergy to fentanyl or ketamine;
• children who are unable to provide pain scale assessment;
• children with chronic pain of greater than 4 weeks;
• Pregnant females;
• and children with a Glasgow Coma Scale (GCS)<15.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maimonides Medical Center

OTHER

Sponsor Role: collaborator

Antonios Likourezos

OTHER

Sponsor Role: lead

Responsible Party

Antonios Likourezos

Research Manager

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sabina Zavolkovskaya, MD

Role: PRINCIPAL_INVESTIGATOR

Maimonides Medical Center

Sergey Motov, MD

Role: STUDY_DIRECTOR

Maimonides Medical Center

John Marshall, MD

Role: STUDY_CHAIR

Maimonides Medical Center

Locations

Maimonides Medical Center

Brooklyn, New York, United States

Countries

United States

References

Andolfatto G, Willman E, Joo D, Miller P, Wong WB, Koehn M, Dobson R, Angus E, Moadebi S. Intranasal ketamine for analgesia in the emergency department: a prospective observational series. Acad Emerg Med. 2013 Oct;20(10):1050-4. doi: 10.1111/acem.12229.

Reference Type: BACKGROUND

PMID: 24127709 (View on PubMed)

Borland M, Jacobs I, King B, O'Brien D. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med. 2007 Mar;49(3):335-40. doi: 10.1016/j.annemergmed.2006.06.016. Epub 2006 Oct 25.

Reference Type: BACKGROUND

PMID: 17067720 (View on PubMed)

Borland ML, Clark LJ, Esson A. Comparative review of the clinical use of intranasal fentanyl versus morphine in a paediatric emergency department. Emerg Med Australas. 2008 Dec;20(6):515-20. doi: 10.1111/j.1742-6723.2008.01138.x.

Reference Type: BACKGROUND

PMID: 19125831 (View on PubMed)

Borland M, Milsom S, Esson A. Equivalency of two concentrations of fentanyl administered by the intranasal route for acute analgesia in children in a paediatric emergency department: a randomized controlled trial. Emerg Med Australas. 2011 Apr;23(2):202-8. doi: 10.1111/j.1742-6723.2011.01391.x. Epub 2011 Feb 8.

Reference Type: BACKGROUND

PMID: 21489168 (View on PubMed)

Garra G, Singer AJ, Taira BR, Chohan J, Cardoz H, Chisena E, Thode HC Jr. Validation of the Wong-Baker FACES Pain Rating Scale in pediatric emergency department patients. Acad Emerg Med. 2010 Jan;17(1):50-4. doi: 10.1111/j.1553-2712.2009.00620.x. Epub 2009 Dec 9.

Reference Type: BACKGROUND

PMID: 20003121 (View on PubMed)

Goldman RD: Intranasal drug delivery for children with acute illness. Curr Drug Ther 2006, 1(1):127-130.

Reference Type: BACKGROUND

Grassin-Delyle S, Buenestado A, Naline E, Faisy C, Blouquit-Laye S, Couderc LJ, Le Guen M, Fischler M, Devillier P. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol Ther. 2012 Jun;134(3):366-79. doi: 10.1016/j.pharmthera.2012.03.003. Epub 2012 Mar 23.

Reference Type: BACKGROUND

PMID: 22465159 (View on PubMed)

Graudins A, Meek R, Egerton-Warburton D, Seith R, Furness T, Chapman R. The PICHFORK (Pain InCHildren Fentanyl OR Ketamine) trial comparing the efficacy of intranasal ketamine and fentanyl in the relief of moderate to severe pain in children with limb injuries: study protocol for a randomized controlled trial. Trials. 2013 Jul 10;14:208. doi: 10.1186/1745-6215-14-208.

Reference Type: BACKGROUND

PMID: 23842536 (View on PubMed)

Holdgate A, Cao A, Lo KM. The implementation of intranasal fentanyl for children in a mixed adult and pediatric emergency department reduces time to analgesic administration. Acad Emerg Med. 2010 Feb;17(2):214-7. doi: 10.1111/j.1553-2712.2009.00636.x.

Reference Type: BACKGROUND

PMID: 20070272 (View on PubMed)

Karlsen AP, Pedersen DM, Trautner S, Dahl JB, Hansen MS. Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study. Ann Emerg Med. 2014 Jun;63(6):699-703. doi: 10.1016/j.annemergmed.2013.10.025. Epub 2013 Nov 22.

Reference Type: BACKGROUND

PMID: 24268523 (View on PubMed)

Miner JR, Kletti C, Herold M, Hubbard D, Biros MH. Randomized clinical trial of nebulized fentanyl citrate versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain. Acad Emerg Med. 2007 Oct;14(10):895-8. doi: 10.1197/j.aem.2007.06.036.

Reference Type: BACKGROUND

PMID: 17898251 (View on PubMed)

National Institute of Clinical Studies: Emergency care acute pain management manual, National Health and Medical Research Council. Canberra, Australia: ACT; 2011.

Reference Type: BACKGROUND

Page MG, Katz J, Stinson J, Isaac L, Martin-Pichora AL, Campbell F. Validation of the numerical rating scale for pain intensity and unpleasantness in pediatric acute postoperative pain: sensitivity to change over time. J Pain. 2012 Apr;13(4):359-69. doi: 10.1016/j.jpain.2011.12.010. Epub 2012 Mar 15.

Reference Type: BACKGROUND

PMID: 22424915 (View on PubMed)

Rickard C, O'Meara P, McGrail M, Garner D, McLean A, Le Lievre P. A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting. Am J Emerg Med. 2007 Oct;25(8):911-7. doi: 10.1016/j.ajem.2007.02.027.

Reference Type: BACKGROUND

PMID: 17920976 (View on PubMed)

Saunders M, Adelgais K, Nelson D. Use of intranasal fentanyl for the relief of pediatric orthopedic trauma pain. Acad Emerg Med. 2010 Nov;17(11):1155-61. doi: 10.1111/j.1553-2712.2010.00905.x.

Reference Type: BACKGROUND

PMID: 21175512 (View on PubMed)

Yeaman F, Meek R, Egerton-Warburton D, Rosengarten P, Graudins A. Sub-dissociative-dose intranasal ketamine for moderate to severe pain in adult emergency department patients. Emerg Med Australas. 2014 Jun;26(3):237-42. doi: 10.1111/1742-6723.12173. Epub 2014 Apr 8.

Reference Type: BACKGROUND

PMID: 24712757 (View on PubMed)

Yeaman F, Oakley E, Meek R, Graudins A. Sub-dissociative dose intranasal ketamine for limb injury pain in children in the emergency department: a pilot study. Emerg Med Australas. 2013 Apr;25(2):161-7. doi: 10.1111/1742-6723.12059. Epub 2013 Mar 20.

Reference Type: BACKGROUND

PMID: 23560967 (View on PubMed)

Other Identifiers

2014-11-20-MMC

Identifier Type: -

Identifier Source: org_study_id