Intranasal Ketamine Versus Subcutaneous Ketamine for Treatment of Post-traumatic Acute Pain in the Emergency Department ( INVESCK )

NCT ID: NCT05229055

Last Updated: 2023-05-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-15

Study Completion Date

2025-12-01

Brief Summary

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Pain is the most common complaint for emergency department (ED) visit. Intranasal ketamine has been shown to provide rapid, well-tolerated, effective analgesia to emergency department (ED) patients with acute pain. few trials have studied ketamine infusion subcutaneously for pain management in trauma patients.

Detailed Description

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Materials and methods :

Study design It is a randomized, prospective, double blind, controlled, multicentric trial.

Study setting and selection of participants :

The trial is conducted in three community teaching hospitals :

* Emergency department, fattouma bourgiba university hospital, monastir, tunisia.
* Emergency department, sahloul university hospital, sousse, tunisia.
* Emergency department, farhat hached university hospital, sousse, tunisia.

Inculsion criteria :

The study includes patients aged 18 to 60 years who presented to the ED with acute limb trauma pain with a visual analgesic scale (VAS) of 5 or more on a standard 11 point (0-10). An informed consent is necessary. Pain was considered traumatic if it is reported as appearing immediately after the trauma and no anterior pain was described in the same limb.

The intranasal route Ketamine solution 250 mg/5ml was used. It was applied intranasally using a nasal spray pump where each spray delivered approximately 0.4 ml of solution corresponding to 20 mg of ketamine. After initial evaluation, each patient having the inclusion criteria receives one pulverisation (0.4 ml) per nostril of ketamine corresponding to a total dose of 20 mg of ketamine. Ketamine dosing was based on previous reports of intranasal ketamine use in ED patients, doses ranged from 0.45mg/kg to 1.25mg/kg.

The subcutaneous route :

Ketamine dosing by subcutanous route was based on previous reports use for post operative pain management. . The results of these reports revealed that low-dose ketamine 20-60 mg (0.5mg/kg for patients weighing 40-120 kg) showed an over all decrease in either the amount of opioid used or the amount of pain experienced. the investigators decided to chose a dose of 20mg of ketamine for all patients administered via 1ml insulin syringe once subcutaneously.

Protocol :

After initial medical evaluation, every patient who meet the inclusion criteria, will receive randomly either subcutaneous or intanasal dose of ketamine as detailed above according to the predetermined randomization. To ensure a double-blind administration of ketamine ; patients enrolled in the intranasal ketamine group will receive concomitantly 1ml of normal saline solution subcutaneously, and patients enrolled in the subcutaneous ketamine group will receive concomitantly a spray of normal saline solution in each nostril. None of the treating physician or nurses are aware about the medication received. The included patients were followed and monitored until their discharge from the ED. All enrolled patients underwent close supervision of study staff to ensure safety. Study investigators record VAS, and adverse effects at 15, 30, 60, 90, and 120 minutes and at ED discharge. During ED stay, patients were monitored in order to evaluate the need for rescue analgesic treatment. At 30 minutes, if patients report a pain numeric rating scale score of 5 or greater and request additional pain relief, titrated morphine is adminstered as a rescue analgesic with a dose of 0.1mg/kg repeated every 3 to 5 minutes if the pain numeric rating scale score is still greater or equal to 3.

. Patients's informed consent is obtained.

Conditions

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Acute Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The intranasal route Ketamine solution was used. Applying a nasal spray pump where each spray delivered 20 mg of ketamine. After initial evaluation, each patient having the inclusion criteria receives one pulverisation (0.4 ml) per nostril of ketamine corresponding to a total dose of 20 mg of ketamine.

The subcutaneous route :

Ketamine dosing by subcutanous route was based on previous reports use for post operative pain management. . The results of these reports revealed that low-dose ketamine 20-60 mg (0.5mg/kg for patients weighing 40-120 kg) showed an over all decrease in either the amount of opioid used or the amount of pain experienced (10, 11). For our study, we decided to chose a dose of 20mg of ketamine for all patients administered via 1ml insulin syringe once subcutaneously.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
After initial medical evaluation, every patient who meet the inclusion criteria, will receive randomly either subcutaneous or intanasal dose of ketamine as detailed above according to the predetermined randomization. To ensure a double-blind administration of ketamine ; patients enrolled in the intranasal ketamine group will receive concomitantly 1ml of normal saline solution subcutaneously, and patients enrolled in the subcutaneous ketamine group will receive concomitantly a spray of normal saline solution in each nostril. None of the treating physician or nurses are aware about the medication received.

Study Groups

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Intranasal ketamine

Ketamine solution 250 mg/5ml was used. It was applied intranasally using a nasal spray pump whereeach spray delivered approximately 0.4 ml of solution corresponding to 20 mg of ketamine. After initial evaluation, each patient having the inclusion criteria receives one pulverisation (0.4 ml) per nostril of ketamine corresponding to a total dose of 20 mg of ketamine. Ketamine dosing was based on previous reports of intranasal ketamine use in ED patients, doses ranged from 0.45mg/kg to 1.25mg/kg (9).

Group Type ACTIVE_COMPARATOR

Ketamine

Intervention Type DRUG

giving ketamine intranasal

subcutanous ketamine

Ketamine dosing by subcutanous route was based on previous reports use for post operative pain management. . The results of these reports revealed that low-dose ketamine 20-60 mg (0.5mg/kg for patients weighing 40-120 kg) showed an over all decrease in either the amount of opioid used or the amount of pain experienced (10, 11).For our study, we decided to chose a dose of 20mg of ketamine for all patients administered via 1ml insulin syringe once subcutaneously.

Group Type ACTIVE_COMPARATOR

Ketamine

Intervention Type DRUG

giving ketamine intranasal

Interventions

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Ketamine

giving ketamine intranasal

Intervention Type DRUG

Other Intervention Names

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ketalar

Eligibility Criteria

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Inclusion Criteria

* • Patients who presented to the ED with acute limb trauma pain with a visual analgesic scale (VAS) of 5 or more on a standard 11 point (0-10).

* Pain was considered traumatic if it is reported as appearing immediately after the trauma and no anterior pain was described in the same limb.

Exclusion Criteria

* Pregnancy/Breastfeeding

* altered mental status (GCS\<15)
* Allergy to ketamine or morphine
* Weight less than 40 kg or greater than 100kg
* Unstable vital signs (systolic blood pressure \<90 or \> 180mmHg, pulse rate\<50 or \>150bpm, and respiration rate \<10 or \>30 breath/min)
* Medical history of acute head or eye injury
* Medical history of seizure
* Medical history of intracranial hypertension,
* Medical history of chronic pain,
* Medical history of severe renal or hepatic insufficiency.
* Medical history of glaucoma
* Alcohol or drug abuse
* Psychiatric illness,
* Recent (4 hours before) analgesic agent use.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Monastir

OTHER

Sponsor Role lead

Responsible Party

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Pr. Semir Nouira

Monastir Emergency departement

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nouira Semir, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Monastir

Locations

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university of Monastir

Monastir, , Tunisia

Site Status RECRUITING

Countries

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Tunisia

Central Contacts

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Nouira Semir, Professor

Role: CONTACT

73106046 ext. 216

Bel Hadj Ali Khaoula, MD

Role: CONTACT

73106000 ext. 216

Facility Contacts

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Nouira Samir, Professor

Role: primary

73532014 ext. +216

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)

Guirimand F, Dupont X, Brasseur L, Chauvin M, Bouhassira D. The effects of ketamine on the temporal summation (wind-up) of the R(III) nociceptive flexion reflex and pain in humans. Anesth Analg. 2000 Feb;90(2):408-14. doi: 10.1097/00000539-200002000-00031.

Reference Type BACKGROUND
PMID: 10648330 (View on PubMed)

Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain. 1999 Aug;82(2):111-125. doi: 10.1016/S0304-3959(99)00044-5.

Reference Type BACKGROUND
PMID: 10467917 (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)

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)

Strigo IA, Duncan GH, Bushnell CM, Boivin M, Wainer I, Rodriguez Rosas EM, Persson J. The effects of racemic ketamine on painful stimulation of skin and viscera in human subjects. Pain. 2005 Feb;113(3):255-264. doi: 10.1016/j.pain.2004.10.023.

Reference Type BACKGROUND
PMID: 15661431 (View on PubMed)

Smith DC, Mader TJ, Smithline HA. Low dose intravenous ketamine as an analgesic: a pilot study using an experimental model of acute pain. Am J Emerg Med. 2001 Oct;19(6):531-2. doi: 10.1053/ajem.2001.27152. No abstract available.

Reference Type BACKGROUND
PMID: 11593484 (View on PubMed)

Andolfatto G, Innes K, Dick W, Jenneson S, Willman E, Stenstrom R, Zed PJ, Benoit G. Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults. Ann Emerg Med. 2019 Aug;74(2):241-250. doi: 10.1016/j.annemergmed.2019.01.048. Epub 2019 Mar 27.

Reference Type BACKGROUND
PMID: 30926189 (View on PubMed)

Shrestha R, Pant S, Shrestha A, Batajoo KH, Thapa R, Vaidya S. Intranasal ketamine for the treatment of patients with acute pain in the emergency department. World J Emerg Med. 2016;7(1):19-24. doi: 10.5847/wjem.j.1920-8642.2016.01.003.

Reference Type BACKGROUND
PMID: 27006733 (View on PubMed)

Tuchscherer J, McKay WP, Twagirumugabe T. Low-dose subcutaneous ketamine for postoperative pain management in Rwanda: a dose-finding study. Can J Anaesth. 2017 Sep;64(9):928-934. doi: 10.1007/s12630-017-0914-0. Epub 2017 Jun 19.

Reference Type BACKGROUND
PMID: 28631150 (View on PubMed)

Elia N, Tramer MR. Ketamine and postoperative pain--a quantitative systematic review of randomised trials. Pain. 2005 Jan;113(1-2):61-70. doi: 10.1016/j.pain.2004.09.036.

Reference Type BACKGROUND
PMID: 15621365 (View on PubMed)

Other Identifiers

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Intranasal ketamine

Identifier Type: -

Identifier Source: org_study_id

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