Ketamine for Pain in the Emergency Department

NCT03896230 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: Pro2018-0970
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This study will prospectively compare the mean Numerical Rating Scale (NRS) pain score reduction amongst three recommended dosing strategies of intravenous ketamine (0.1 mg/kg, 0.2 mg/kg, and 0.3mg/kg) for acute pain in the emergency department (ED).This study will also examine the frequency of adverse events secondary to ketamine including fatigue, dizziness, nausea, headache, feeling of unreality, changes in hearing or vision, mood changes, generalized discomfort, and hallucinations, changes in vital signs. Subgroups for exploratory analysis based on the need for rescue analgesia within two hours of ketamine administration, adequate pain relief, previous opioid tolerance, and age (adults \< 65 years old and \> 65 years old).

Conditions

Acute Pain

Keywords

moderate to severe pain; emergency department patient; ketamine

Outcome Measures

Primary Outcomes (1)

• Pain Score

  Pain score using Numerical Rating Scale (NRS) post ketamine infusion. The Numerical Rating Scale (NRS) ranges from 0-to-10 with 0 being no pain and lower numbers representing less pain, so in this case lower numbers will represent better outcomes. Pain scores were reported at baseline and then at 15 min/30 min/60 min/90 min and 120 minutes post-infusion.

  Within 2 hours post infusion completion

Secondary Outcomes (1)

• Adverse Events

  Within 2 hours post infusion completion

Study Arms (3)

Arm 1: 0.1 mg/kg ketamine

ACTIVE COMPARATOR

0.1 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion.

Drug: Ketamine Injectable Product

Arm 1: 0.2 mg/kg ketamine

ACTIVE COMPARATOR

0.2 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion.

Drug: Ketamine Injectable Product

Arm 1: 0.3 mg/kg ketamine

ACTIVE COMPARATOR

0.3 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion.

Drug: Ketamine Injectable Product

Interventions

Ketamine Injectable Product DRUG

Three different doses of ketamine will be administered.

Arm 1: 0.1 mg/kg ketamine; Arm 1: 0.2 mg/kg ketamine; Arm 1: 0.3 mg/kg ketamine

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute pain (including acute on chronic pain)
• Pain score of moderate to severe (\> 4/10) on the Numerical Rating Scale
• Provider determines the patient requires intravenous ketamine for analgesia

You may not qualify if:

• History of hypersensitivity to ketamine
• Altered mental status
• Psychiatric illness
• Known history of renal or hepatic insufficiency
• Acute head or eye injury
• Suspected intracranial hypertension or mass
• Headache as the chief complaint
• Alcohol or drug abuse
• Received an analgesic within the last four hours
• History of congestive heart failure
• History of aortic or brain aneurysm
• Active Chest Pain
• Porphyria
• Active methadone treatment
• Pregnant or breastfeeding

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (1)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (25)

• Todd KH, Ducharme J, Choiniere M, Crandall CS, Fosnocht DE, Homel P, Tanabe P; PEMI Study Group. Pain in the emergency department: results of the pain and emergency medicine initiative (PEMI) multicenter study. J Pain. 2007 Jun;8(6):460-6. doi: 10.1016/j.jpain.2006.12.005. Epub 2007 Feb 15.

  PMID: 17306626 BACKGROUND

• 2. American College of Emergency Physicians Policy Statement. Optimizing the treatment of acute pain in the emergency department. Ann Emerg Med. 2017;70:446-8.

  BACKGROUND

• 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: 28285863 BACKGROUND

• Crane EH. Highlights of the 2011 Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits. 2013 Feb 22. In: The CBHSQ Report. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2013-. Available from http://www.ncbi.nlm.nih.gov/books/NBK384680/

  PMID: 27631059 BACKGROUND

• Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016 Jan 1;64(50-51):1378-82. doi: 10.15585/mmwr.mm6450a3.

  PMID: 26720857 BACKGROUND

• 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.

  PMID: 24127709 BACKGROUND

• Gorlin AW, Rosenfeld DM, Ramakrishna H. Intravenous sub-anesthetic ketamine for perioperative analgesia. J Anaesthesiol Clin Pharmacol. 2016 Apr-Jun;32(2):160-7. doi: 10.4103/0970-9185.182085.

  PMID: 27275042 BACKGROUND

• Scheppke KA, Braghiroli J, Shalaby M, Chait R. Prehospital use of i.m. ketamine for sedation of violent and agitated patients. West J Emerg Med. 2014 Nov;15(7):736-41. doi: 10.5811/westjem.2014.9.23229. Epub 2014 Nov 11.

  PMID: 25493111 BACKGROUND

• Motov S, Mann S, Drapkin J, Butt M, Likourezos A, Yetter E, Brady J, Rothberger N, Gohel A, Flom P, Mai M, Fromm C, Marshall J. Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A randomized controlled trial. Am J Emerg Med. 2019 Feb;37(2):220-227. doi: 10.1016/j.ajem.2018.05.030. Epub 2018 May 16.

  PMID: 29807629 BACKGROUND

• 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: 25377395 BACKGROUND

• 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: 25817884 BACKGROUND

• 12. American College of Emergency Physicians. "Sub-Dissociative Ketamine for Analgesia". Policy Resource and Education Paper. November 2017.

  BACKGROUND

• Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806.

  PMID: 29870457 BACKGROUND

• 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: 28821365 BACKGROUND

• 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: 28177167 BACKGROUND

• Clattenburg EJ, Hailozian C, Haro D, Yoo T, Flores S, Louie D, Herring AA. Slow Infusion of Low-dose Ketamine Reduces Bothersome Side Effects Compared to Intravenous Push: A Double-blind, Double-dummy, Randomized Controlled Trial. Acad Emerg Med. 2018 Sep;25(9):1048-1052. doi: 10.1111/acem.13428. Epub 2018 May 25.

  PMID: 29645317 BACKGROUND

• 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.

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• Jahanian F, Hosseininejad SM, Amini Ahidashti H, Bozorgi F, Goli Khatir I, Montazar SH, Azarfar V. Efficacy and Safety of Morphine and Low Dose Ketamine for Pain Control of Patients with Long Bone Fractures: A Randomized, Double-Blind, Clinical Trial. Bull Emerg Trauma. 2018 Jan;6(1):31-36. doi: 10.29252/beat-060105.

  PMID: 29379807 BACKGROUND

• Mahshidfar B, Mofidi M, Fattahi M, Farsi D, Hafezi Moghadam P, Abbasi S, Rezai M. Acute Pain Management in Emergency Department, Low Dose Ketamine Versus Morphine, A Randomized Clinical Trial. Anesth Pain Med. 2017 Dec 26;7(6):e60561. doi: 10.5812/aapm.60561. eCollection 2017 Dec.

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• Majidinejad S, Esmailian M, Emadi M. Comparison of Intravenous Ketamine with Morphine in Pain Relief of Long Bones Fractures: a Double Blind Randomized Clinical Trial. Emerg (Tehran). 2014 Spring;2(2):77-80.

  PMID: 26495351 BACKGROUND

• 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: 25624076 BACKGROUND

• Motov S, Mai M, Pushkar I, Likourezos A, Drapkin J, Yasavolian M, Brady J, Homel P, Fromm C. A prospective randomized, double-dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of pain in the ED. Am J Emerg Med. 2017 Aug;35(8):1095-1100. doi: 10.1016/j.ajem.2017.03.004. Epub 2017 Mar 3.

  PMID: 28283340 BACKGROUND

• Sin B, Tatunchak T, Paryavi M, Olivo M, Mian U, Ruiz J, Shah B, de Souza S. The Use of Ketamine for Acute Treatment of Pain: A Randomized, Double-Blind, Placebo-Controlled Trial. J Emerg Med. 2017 May;52(5):601-608. doi: 10.1016/j.jemermed.2016.12.039. Epub 2017 Mar 6.

  PMID: 28279542 BACKGROUND

• 24. Ketalar [package insert]. Chestnut Ridge, NY. Par Pharmaceutical.

  BACKGROUND

• 25. Food and Drug Administration (FDA). Extended-release (ER) and long-acting (LA) opioid analgesics Risk Evaluation and Mitigation Strategy (REMS). www.fda.gov/downloads/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm311290.pdf. Accessed September 20th, 2018.

  BACKGROUND

MeSH Terms

Conditions

Acute Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was initiated in 2019 and was then put on hold because of COVID. Post-COVID, the study was opened to enrollment again but due to limited resources and lack of enrollment, the study was terminated.

Results Point of Contact

• Title: Gabrielle L. Procopio, Pharm.D., BCPS
• Organization: Hackensack Meridian Health

Gabrielle.Procopio@hmhn.org

551-996-4368

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded study (only the pharmacist supervisor that has no other involvement with the study will know the dose)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3 arms each arm getting a different dose of ketamine

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: March 29, 2019
• Study Start: May 3, 2019
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: June 7, 2023
• Results First Posted: June 7, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)