Ketamine for Pain in the Emergency Department

NCT ID: NCT03896230

Last Updated: 2023-06-07

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-03

Study Completion Date

2019-12-20

Brief Summary

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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).

Detailed Description

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A literature review was performed that searched for randomized clinical trials involving ketamine IV boluses for acute pain in the Emergency Department. Studies involving continuous infusions or intranasal routes of ketamine administration were not included. Thirteen randomized clinical trials were identified meeting this criteria. None of these trials directly compared ketamine doses within the 0.1-0.3 mg/kg range for pain score reduction and adverse events. Many of these trials concluded with the recommendation that further studies were needed to evaluate the optimal dosing of ketamine for acute pain and determine which populations are most ideal for its use. This study will be the first to evaluate ketamine for acute pain in the emergency department at standard of care doses (0.1 mg/kg, 0.2 mg/kg, and 0.3 mg/kg IV) to determine which dose correlates with the most efficacy and safety.

This study will include the following procedures:

* Patient consent, screening, and enrollment will be performed by the treating resident or attending who will remain blinded
* Patient will be assigned a subject number
* Treating resident or attending will notify the ED pharmacist that a patient has been enrolled in the trial
* ED pharmacist will notify the IV room and place the study drug order
* Either the ED pharmacist or a pharmacy supervisor will randomize the subject based on the predetermined randomization list
* Study drug will be prepared as 0.1 mg/kg, 0.2 mg/kg, or 0.3 mg/kg IV dose in a 100 mL solution of dextrose 5% or sodium chloride 0.9%
* ED pharmacist will promptly deliver the study drug to the ED
* Baseline vital signs will be assessed prior to starting the study drug infusion
* Study drug will be administered via IV infusion over 20 minutes
* Treating resident or attending will reassess the patient at 15 minutes from the end of infusion, at 30 minutes from the end of infusion, and then every 30 minutes for up to 120 minutes or until discharge, whichever is sooner

Conditions

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Acute Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

3 arms each arm getting a different dose of ketamine
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blinded study (only the pharmacist supervisor that has no other involvement with the study will know the dose)

Study Groups

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Arm 1: 0.1 mg/kg ketamine

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.

Group Type ACTIVE_COMPARATOR

Ketamine Injectable Product

Intervention Type DRUG

Three different doses of ketamine will be administered.

Arm 1: 0.2 mg/kg ketamine

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.

Group Type ACTIVE_COMPARATOR

Ketamine Injectable Product

Intervention Type DRUG

Three different doses of ketamine will be administered.

Arm 1: 0.3 mg/kg ketamine

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.

Group Type ACTIVE_COMPARATOR

Ketamine Injectable Product

Intervention Type DRUG

Three different doses of ketamine will be administered.

Interventions

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Ketamine Injectable Product

Three different doses of ketamine will be administered.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Signs of respiratory, hemodynamic, or neurologic compromise

* Systolic blood pressure \< 90 mmHg or \> 180 mmHg
* Heart rate \< 50 beats per minute or \> 150 beats per minute
* Respiratory rate \< 10 breaths per minute or \> 30 breaths per minute
* Glasgow Coma Score \< 15
* Previously received ketamine \< 0.3 mg/kg IV for acute pain in the emergency department
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hackensack Meridian Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 17306626 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 28285863 (View on PubMed)

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/

Reference Type BACKGROUND
PMID: 27631059 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26720857 (View on PubMed)

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)

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.

Reference Type BACKGROUND
PMID: 27275042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25493111 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29807629 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25377395 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25817884 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 29870457 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28821365 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28177167 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29645317 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17499654 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29379807 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29696126 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26495351 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25624076 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28283340 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28279542 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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Pro2018-0970

Identifier Type: -

Identifier Source: org_study_id

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