Low-dose KETamine as an Adjunct to MOrphine for Acute Pain in the ED

Study Overview
=================
Brief Summary
-----------------
The KetMo study is an investigator-initiated, randomized, parallel group, double blinded trial investigating if ketamine as an adjunct to morphine improves pain treatment in the ED. Patients in pain (assessed on NRS, 5 or more) will be randomized to low-dose ketamine or placebo as an adjunct to morphine. Patients with or without prior use of opioids will be randomized separately. The primary outcome will be pain reduction, assessed on NRS, after 10 minutes. Secondary outcomes include pain reduction until 120 minutes after injection of study medicine, need for rescue opioid, side effects and patient- and provider satisfaction.

Official Title
-----------------
Low-dose KETamine as an Adjunct to MOrphine for Acute Pain in the ED: a Randomized, Double-blinded Clinical Trial

Conditions
-----------------
Acute Pain, Opioid Use

Intervention / Treatment
-----------------
* Drug: low dose ketamine
* Drug: Placebo (saline)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Emergency Department admission Age ≥ 18 years NRS ≥ 5 Stable vital signs defined as systolic blood pressure ≥ 90 mmHg, heart rate between 60 and 150 per minute, respiratory rate between 8 and 26 per minute, oxygen saturation greater than or equal to 92% Exclusion Criteria: Initial management by trauma-team Systolic blood pressure ≥ 180mmHg, severe untreated arrhythmia, unstable angina, recent myocardial infarction (< 30 days), severe heart-failure (Ejection fraction < 40 %) Symptoms of untreated hyperthyroidism Cirrhosis with ascites Known/suspected pregnancy or breastfeeding Patients for whom consent is not obtainable or psychiatric forced treatment. Previously enrolled in the trial Psychiatric illness prior to admission defined as prior psychosis/schizophrenia Untreated diagnosed glaucoma Known hypersensitivity to ketamine or to any excipient or prior use of ketamine with a negative experience (i.e. hallucinations) Patient clearly influenced by drugs or alcohol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention, low-dose ketamine<br>Two 1 ml syringes with Esketamine (5 mg/ml) will be prepared and study drug will be administered as intravenous bolus dose, 0,1 mg/kg. The study drug will be administered after an intravenous morphine dose. | Drug: low dose ketamine<br>* Low dose ketamine 0.1 mg/kg Product: Esketamin Orifarm 5 mg/ml<br>|
| Placebo Comparator: Placebo<br>Two 1 ml syringes with saline will be prepared and study drug will be administered as intravenous dose, same volume as if Esketamine. The placebo drug will be administered after an intravenous morphine dose. | Drug: Placebo (saline)<br>* Isotonic Saline<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain reduction after 10 minutes assessed on numeric rating scale, NRS | Numeric Rating Scale, 0-10 | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity assessed on numeric rating scale, NRS |  | 120 minutes | 
| Need for rescue opioid | any kind of opioid | 120 minutes | 
| Side effects | At each time point (10 min, 20 min, 30 min, 45 min, 60 min and 120) vital parameters are measured (Blood pressure, Respiratory Frequency, Saturation, Heart Rate) and the patient are asked if they experience nausea/vomiting, a dream like state/dissociation/out of body experience, anxiety or dizziness. Besides a objective RASS score +4 to -5 (combative/very agitated/agitated/restless/aler and calm/drowsy/light sedation/moderate sedation/deep sedation/unarousable | 120 minutes | 
| Patient satisfaction | Lickert scale | 120 minutes | 
| Provider satisfaction | Lickert scale | 120 minutes | 
| Comparison af pain reduction ( prior use of opioid vs no prior use of opioid |  | 120 minutes | 
| Patient Rated Pain Relief | 6 point lickert scale - worse pain, no pain relief, little pain relief, moderate pain relief, good pain relief, complete pain relief. | Patient are asked at timepoint 10 and timepoint 120 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Low dose ketamine, Opioid use, Acute pain, Emergency Department