Low Dose Ketamine Intra Nasal Traumatology (Ket)

Intranasal Ketamine for Treatment of Acute Pain in the Emergency Department : A Randomized Controlled Trial

To evaluate the efficacy and safety of early administration of low-dose intranasal ketamine analgesic agents in patients with moderate to severe pain in the ED in reducing the need for opioid or non opioids analgesic agents.

Study Overview

• Status: Completed
• Conditions: Trauma
• Intervention / Treatment: Drug: Placebo; Drug: Ketamine

Detailed Description

Intranasal ketamine for treatment of acute pain in the emergency department : A randomized controlled trial

Introduction :

Pain is the most common complaint for emergency department (ED) visits [1].The provision of adequate, safe, and timely analgesia is a core component of patient care in the emergency department (ED). Ketamine is a noncompetitive Nmethyl- D-aspartate and glutamate receptor antagonist that decreases central sensitization, "wind-up" phenomena, and pain memory [2,3].

At subdissociative doses (0.1 to 0.6 mg/kg; most commonly 0.3 mg/kg) maintains potent analgesic and amnestic effects that are accompanied by preservation of protective airway reflexes, spontaneous respiration, and cardiopulmonary stability [4-6].

Intranasal route ….

Objective of the study :

To evaluate the efficacy and safety of early administration of low-dose intranasal ketamine analgesic agents in patients with moderate to severe pain in the ED in reducing the need for opioid or class III analgesic agents.

Materials and Methods :

Study design :

It is a ramdomized, prospective, double blind, controlled, multicentric trial. The study is registered with clinical.tria.gov (…….).

Study Setting and Selection of Participants :

The trial is conducted in three community teaching hospitals :

• Emergency department, fattouma bourguiba university hospital, monastir, tunisia
• Emergency department, sahloul university hospital, sousse, tunisia
• Emergency department, farhat hached university hospital, sousse, tunisia

ED principal investigators maintain the randomization list, which is generated before the start of the study, prepare the medication, and deliver it to the treating physician in a blinded manner.

Inclusion criteria :

The study includes patients aged 18 to 80 years who presented to the ED with acute limb trauma pain with a visual analogue scale (VAS) of 5 or more on a standard 11- point (0 to 10). An informed consent is necessary.

Exclusion criteria :

• Pregnancy,
• Breast-feeding,
• Altered mental status,
• Allergy to ketamine or morphine or
• Weight less than 46 kg or greater than 115 kg,
• Unstable vital signs (systolic blood pressure <90 or >180 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min),
• Medical history of acute head or eye injury, seizure, intracranial hypertension, chronic pain, severre renal or hepatic insufficiency,
• Alcohol or drug abuse,
• Psychiatric illness,
• Recent (4 hours before) analgesic agent use.

Protocol :

In the triage area, each patient having the inclusion criteria receives 25mg of ketamine in 0.5 ml of serum saline in one pulverisation per nostril or 0.5 mL of normal saline solution in one pulverisation per nostril as a placebo according to the predetermined randomization list. None of the treating physician or nurses is aware about the medication received. In all patients included, the investigators collect vital signs ; demographic and clinical data.

Study investigators record VAS, and adverse effects at 15, 30, 60, 90, and 120 minutes.

At 30 minutes, if patients report a pain numeric rating scale score of 5 or greater and request additional pain relief, titrated morphine is administered as a rescue analgesic with a dose of 0.1 mg/Kg repeated every 3 to 5 minutes if the pain numeric rating scale score is still greater or equal to 3.

All data recorded on data collection sheets, including sex, demographics, medical history, and vital signs, were entered into SPSS (version 20.0; IBM Corp) by the research manager.

Patients's informed consent is obtained. The ethic commitee of our institution approved the study.

Endpoints :

Primary endpoints :

- Need for rescue opioids during ED stay

Secondary endpoints :

• requirement of non-opioids analgesic agents.
• percentage of patients discharged from the ED with VAS <30.
• Safety : adverse events

• Study Type: Interventional
• Enrollment (Actual): 1102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Tunisia
  • Monastir, Tunisia, 5000
    • Emergency department of university hospital Fattouma Bourguiba of Monastir
  • Emergency Department Monastir, Tunisia 5000
    • Monastir, Emergency Department Monastir, Tunisia 5000, Tunisia, 5000
      • Nouira Samir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The study includes patients aged 18 to 80 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 to 10). An informed consent is necessary.

Exclusion Criteria:

• - Pregnancy,
• Breast-feeding,
• Altered mental status,
• Allergy to ketamine or morphine or
• Weight less than 46 kg or greater than 115 kg,
• Unstable vital signs (systolic blood pressure <90 or >180 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min),
• Medical history of acute head or eye injury, seizure, intracranial hypertension, chronic pain, severre renal or hepatic insufficiency,
• Alcohol or drug abuse,
• Psychiatric illness,
• Recent (4 hours before) analgesic agent use.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo group; Intranasal placebo pulverisation	Drug: Placebo; 0.5 mL of normal saline solution as a placebo in one pulverisation per nostril; Other Names: normal saline solution
ACTIVE_COMPARATOR: Ketamine group; Intranasal ketamine pulverisation	Drug: Ketamine; 25mg of ketamine in 0.5 ml of serum saline in one pulverisation per nostril is received

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and percentage of patients who need rescue opiods in the two groups	the need for rescue opioids during ED stay	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intolerance to treatement and adverse events	Noticing any sign of intolerance due to treatement : Dizziness , Vomiting..	30 minutes and at 120 minutes
Percentage of patients with VAS <30 mm at discharge	percentage of patients discharged from the ED with VAS <30.	120 minutes
Number and percentage of patients who required non opiods analgesics	Requirement of non-opioids analgesic agents	30 minutes

Collaborators and Investigators

• Sponsor: University of Monastir

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2018
• Primary Completion (ACTUAL): December 1, 2018
• Study Completion (ACTUAL): December 1, 2018

Study Registration Dates

• First Submitted: May 14, 2017
• First Submitted That Met QC Criteria: July 25, 2017
• First Posted (ACTUAL): July 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 30, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Ketamine-Intranasal-Acute pain-Emergency departement
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: Ket-Int-Nas-TR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No