NCT03959852

Brief Summary

The objective of this study is to evaluate the potential opioid-sparing effect associated with the novel combination of fentanyl and sub-dissociative ketamine in adult patients with moderate to severe pain in the emergency department.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Nov 2019

Shorter than P25 for phase_4

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 12, 2019

Completed
2 months until next milestone

First Posted

Study publicly available on registry

May 22, 2019

Completed
6 months until next milestone

Study Start

First participant enrolled

November 18, 2019

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 5, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 5, 2020

Completed
Last Updated

September 11, 2020

Status Verified

September 1, 2020

Enrollment Period

7 months

First QC Date

March 12, 2019

Last Update Submit

September 9, 2020

Conditions

Pain, Acute

Keywords

ModerateSeverePain

Outcome Measures

Primary Outcomes (3)

  • Analgesia of combination fentanyl and SDK as assessed using the pain scale 1-10

    Analgesia of combination fentanyl and SDK as assessed using the pain scale 1-10

    ED encounter (less than 24 hours)

  • Analgesia of fentanyl as assessed using the pain scale 1-10

    Analgesia of fentanyl as assessed using the pain scale 1-10

    ED encounter (less than 24 hours)

  • Analgesia of ketamine as assessed using the pain scale 1-10

    Analgesia of katamine as assessed using the pain scale 1-10

    ED encounter (less than 24 hours)

Secondary Outcomes (2)

  • OARRS report

    ED encounter (less than 24 hours)

  • Opioid sparing response as assessed by number of times additional rescue doses of fentanyl were required

    ED encounter (less than 24 hours)

Study Arms (3)

Sub-Dissociative Ketamine alone

ACTIVE COMPARATOR

0.3 mg/kg of Sub-Dissociative Ketamine IV administered over at least 1 minute

Drug: Ketamine

Fentanyl alone

ACTIVE COMPARATOR

1 mg/kg of Fentanyl IV administered over at least 1 minute

Drug: Fentanyl

Sub-dissociative Ketamine and Fentanyl

EXPERIMENTAL

Combined dose of 0.15 mg/kg of Sub-dissociative Ketamine and 0.5 mg/kg of Fentanyl IV administered over at least 1 minute

Combination Product: Fentanyl and Ketamine

Interventions

FentanylDRUG

1 mg/kg of Fentanyl IV administered over at least 1 minute

Also known as: Fentanyl Citrate
Fentanyl alone
Fentanyl and KetamineCOMBINATION_PRODUCT

Combined dose of 0.15 mg/kg of Sub-dissociative Ketamine and 0.5 mg/kg of Fentanyl IV administered over at least 1 minute.

Sub-dissociative Ketamine and Fentanyl
KetamineDRUG

0.3 mg/kg of Sub-Dissociative Ketamine IV administered over at least 1 minute

Also known as: Ketamine Hydrochloride
Sub-Dissociative Ketamine alone

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years old
  • Moderate pain defined as 4-6 out of 10, severe pain defined as ≥ 7 out of 10 as defined by the numeric rating pain scale (NRS)
  • Proficient in reading and understanding English
  • Are deemed by the attending physician to require opioid therapy.

You may not qualify if:

  • Inability to give consent,
  • Inability to use the numeric rating scale (NRS) score
  • Long-term use of opioids, history of chronic pain
  • Known substance abuse known as excessive use of a drug such as (e.g. alcohol, narcotics or cocaine)
  • Known hypersensitivity to ketamine or fentanyl
  • Pregnancy
  • Alcohol intoxication
  • Depression
  • Anxiety
  • Chronic obstructive pulmonary disease
  • Asthma
  • Cirrhosis
  • On dialysis
  • Acute ischemic stroke
  • Heart rate (HR) less \< 60 bpm or \> 120 bpm
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

St. Elizabeth Boardman Hospital

Boardman, Ohio, 44512, United States

Location

Related Publications (24)

  • Hebsgaard S, Mannering A, Zwisler ST. Assessment of acute pain in trauma-A retrospective prehospital evaluation. J Opioid Manag. 2016 Sep/Oct;12(5):347-353. doi: 10.5055/jom.2016.0351.

    PMID: 27844474BACKGROUND

  • Motov SM, Nelson LS. Advanced Concepts and Controversies in Emergency Department Pain Management. Anesthesiol Clin. 2016 Jun;34(2):271-85. doi: 10.1016/j.anclin.2016.01.006.

    PMID: 27208710BACKGROUND

  • Todd KH. A Review of Current and Emerging Approaches to Pain Management in the Emergency Department. Pain Ther. 2017 Dec;6(2):193-202. doi: 10.1007/s40122-017-0090-5. Epub 2017 Nov 10.

    PMID: 29127600BACKGROUND

  • Bowers KJ, McAllister KB, Ray M, Heitz C. Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial. Acad Emerg Med. 2017 Jun;24(6):676-685. doi: 10.1111/acem.13172. Epub 2017 Mar 22.

    PMID: 28177167BACKGROUND

  • Duncan C, Riley B. BET 2: Low-dose ketamine for acute pain in the ED. Emerg Med J. 2016 Dec;33(12):892-893. doi: 10.1136/emermed-2016-206440.2.

    PMID: 27864394BACKGROUND

  • Jennings PA, Cameron P, Bernard S, Walker T, Jolley D, Fitzgerald M, Masci K. Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial. Emerg Med J. 2014 Oct;31(10):840-3. doi: 10.1136/emermed-2013-202862. Epub 2013 Jul 13.

    PMID: 23851034BACKGROUND

  • Lee EN, Lee JH. The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis. PLoS One. 2016 Oct 27;11(10):e0165461. doi: 10.1371/journal.pone.0165461. eCollection 2016.

    PMID: 27788221BACKGROUND

  • Miller JP, Schauer SG, Ganem VJ, Bebarta VS. Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. Am J Emerg Med. 2015 Mar;33(3):402-8. doi: 10.1016/j.ajem.2014.12.058. Epub 2015 Jan 7.

    PMID: 25624076BACKGROUND

  • Motov S, Rockoff B, Cohen V, Pushkar I, Likourezos A, McKay C, Soleyman-Zomalan E, Homel P, Terentiev V, Fromm C. Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2015 Sep;66(3):222-229.e1. doi: 10.1016/j.annemergmed.2015.03.004. Epub 2015 Mar 26.

    PMID: 25817884BACKGROUND

  • Motov S, Rosenbaum S, Vilke GM, Nakajima Y. Is There a Role for Intravenous Subdissociative-Dose Ketamine Administered as an Adjunct to Opioids or as a Single Agent for Acute Pain Management in the Emergency Department? J Emerg Med. 2016 Dec;51(6):752-757. doi: 10.1016/j.jemermed.2016.07.087. Epub 2016 Sep 29.

    PMID: 27693070BACKGROUND

  • Pourmand A, Mazer-Amirshahi M, Royall C, Alhawas R, Shesser R. Low dose ketamine use in the emergency department, a new direction in pain management. Am J Emerg Med. 2017 Jun;35(6):918-921. doi: 10.1016/j.ajem.2017.03.005. Epub 2017 Mar 2.

    PMID: 28285863BACKGROUND

  • Sin B, Ternas T, Motov SM. The use of subdissociative-dose ketamine for acute pain in the emergency department. Acad Emerg Med. 2015 Mar;22(3):251-7. doi: 10.1111/acem.12604. Epub 2015 Feb 25.

    PMID: 25716117BACKGROUND

  • Abbasi S, Bidi N, Mahshidfar B, Hafezimoghadam P, Rezai M, Mofidi M, Farsi D. Can low-dose of ketamine reduce the need for morphine in renal colic? A double-blind randomized clinical trial. Am J Emerg Med. 2018 Mar;36(3):376-379. doi: 10.1016/j.ajem.2017.08.026. Epub 2017 Aug 14.

    PMID: 28821365BACKGROUND

  • Ahern TL, Herring AA, Miller S, Frazee BW. Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain. Pain Med. 2015 Jul;16(7):1402-9. doi: 10.1111/pme.12705. Epub 2015 Feb 3.

    PMID: 25643741BACKGROUND

  • Dickenson AH. NMDA receptor antagonists: interactions with opioids. Acta Anaesthesiol Scand. 1997 Jan;41(1 Pt 2):112-5. doi: 10.1111/j.1399-6576.1997.tb04624.x.

    PMID: 9061093BACKGROUND

  • Galinski M, Dolveck F, Combes X, Limoges V, Smail N, Pommier V, Templier F, Catineau J, Lapostolle F, Adnet F. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007 May;25(4):385-90. doi: 10.1016/j.ajem.2006.11.016.

    PMID: 17499654BACKGROUND

  • Lilius TO, Jokinen V, Neuvonen MS, Niemi M, Kalso EA, Rauhala PV. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat. Br J Pharmacol. 2015 Jun;172(11):2799-813. doi: 10.1111/bph.12974.

    PMID: 25297798BACKGROUND

  • Wiesenfeld-Hallin Z. Combined opioid-NMDA antagonist therapies. What advantages do they offer for the control of pain syndromes? Drugs. 1998 Jan;55(1):1-4. doi: 10.2165/00003495-199855010-00001.

    PMID: 9463786BACKGROUND

  • Ahern TL, Herring AA, Stone MB, Frazee BW. Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain. Am J Emerg Med. 2013 May;31(5):847-51. doi: 10.1016/j.ajem.2013.02.008. Epub 2013 Apr 18.

    PMID: 23602757BACKGROUND

  • Ahmadi O, Isfahani MN, Feizi A. Comparing low-dose intravenous ketamine-midazolam with intravenous morphine with respect to pain control in patients with closed limb fracture. J Res Med Sci. 2014 Jun;19(6):502-8.

    PMID: 25197290BACKGROUND

  • Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014 Nov;21(11):1193-202. doi: 10.1111/acem.12510.

    PMID: 25377395BACKGROUND

  • Bossard AE, Guirimand F, Fletcher D, Gaude-Joindreau V, Chauvin M, Bouhassira D. Interaction of a combination of morphine and ketamine on the nociceptive flexion reflex in human volunteers. Pain. 2002 Jul;98(1-2):47-57. doi: 10.1016/s0304-3959(01)00472-9.

    PMID: 12098616BACKGROUND

  • Jennings PA, Cameron P, Bernard S, Walker T, Jolley D, Fitzgerald M, Masci K. Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial. Ann Emerg Med. 2012 Jun;59(6):497-503. doi: 10.1016/j.annemergmed.2011.11.012. Epub 2012 Jan 13.

    PMID: 22243959BACKGROUND

  • Johansson P, Kongstad P, Johansson A. The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting. Scand J Trauma Resusc Emerg Med. 2009 Nov 27;17:61. doi: 10.1186/1757-7241-17-61.

    PMID: 19943920BACKGROUND

Related Links

MeSH Terms

Conditions

Acute PainLymphoma, FollicularPain

Interventions

FentanylKetamine

Condition Hierarchy (Ancestors)

Neurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

PiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • David Gemmel

    Director of Research

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 12, 2019

First Posted

May 22, 2019

Study Start

November 18, 2019

Primary Completion

June 5, 2020

Study Completion

June 5, 2020

Last Updated

September 11, 2020

Record last verified: 2020-09

Locations

US(1)