Clinical trial NCT03233035: Low Dose Ketamine Intra Nasal Traumatology
Official title: Intranasal Ketamine for Treatment of Acute Pain in the Emergency Department : A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Trauma
Keywords: Ketamine-Intranasal-Acute pain-Emergency departement
Lead sponsor: University of Monastir
Sponsor class: OTHER
First posted: 2017-07-28
Enrollment: 1102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double Blind Study
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number and percentage of patients who need rescue opiods in the two groups
timeFrame: 30 minutes
Secondary outcomes:
measure: Intolerance to treatement and adverse events
timeFrame: 30 minutes and at 120 minutes
measure: Percentage of patients with VAS <30 mm at discharge
timeFrame: 120 minutes
measure: Number and percentage of patients who required non opiods analgesics
timeFrame: 30 minutes
Other outcomes:
Locations:
city: Monastir
country: Tunisia
facility: Nouira Samir
state: Emergency Department Monastir, Tunisia 5000
city: Monastir
country: Tunisia
facility: Emergency department of university hospital Fattouma Bourguiba of Monastir
Study officials:
affiliation: university Hospital of Monastir
name: Nouira Semir, Professor
role: PRINCIPAL_INVESTIGATOR
References: