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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Pain; Opioid Use
• Intervention / Treatment: Drug: low dose ketamine; Drug: Placebo (saline)

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Vælg En Region, Stat Eller Provins.
    • Aarhus N, Vælg En Region, Stat Eller Provins., Denmark, 8200
      • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Emergency Department admission
2. Age ≥ 18 years
3. NRS ≥ 5
4. 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:

1. Initial management by trauma-team
2. Systolic blood pressure ≥ 180mmHg, severe untreated arrhythmia, unstable angina, recent myocardial infarction (< 30 days), severe heart-failure (Ejection fraction < 40 %)
3. Symptoms of untreated hyperthyroidism
4. Cirrhosis with ascites
5. Known/suspected pregnancy or breastfeeding
6. Patients for whom consent is not obtainable or psychiatric forced treatment.
7. Previously enrolled in the trial
8. Psychiatric illness prior to admission defined as prior psychosis/schizophrenia
9. Untreated diagnosed glaucoma
10. Known hypersensitivity to ketamine or to any excipient or prior use of ketamine with a negative experience (i.e. hallucinations)
11. Patient clearly influenced by drugs or alcohol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention, low-dose ketamine; 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; Low dose ketamine 0.1 mg/kg Product: Esketamin "Orifarm" 5 mg/ml
Placebo Comparator: Placebo; 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); Isotonic Saline

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; Central Denmark Region
• Investigators: Principal Investigator: Stine F Galili, MD, Aarhus University Hospital

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2022
• Primary Completion (Actual): August 15, 2023
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Emergency Department; Acute pain; Opioid use; Low dose ketamine
• 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: KetMO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Six month after the publication of the last results, all de-identified individual patient data will be made available for data sharing
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

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