Morphine or Ketamine for Analgesia (MoKA)

Efficacy of Intravenous Sub-Dissociative Ketamine Versus Intravenous Morphine in Children With Acute Pain

Pain is common in children presenting to the emergency department but is frequently undertreated, leading to both short- and long-term consequences. Morphine is the standard treatment for children with moderate to severe acute pain, but its use is associated with serious side effects and caregiver and clinician concerns related to opioid administration. The investigators aim to determine if sub-dissociative ketamine is non-inferior to morphine for treating acute pain and a preferable alternative for treating acute pain in children because of its more favorable side effect profile and potential long-term benefits related to pain-related function, analgesic use/misuse, and mental and behavioral health outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain; Abdominal Pain; Pediatrics; Isolated Extremity Fracture
• Intervention / Treatment: Drug: Ketamine hydrochloride; Drug: Morphine sulphate

Detailed Description

Aim 1: To determine if IV sub-dissociative ketamine is non-inferior to IV morphine for decreasing pain intensity in children presenting to an ED with acute pain. The investigators hypothesize that IV sub-dissociative ketamine is non-inferior to IV morphine for decreasing pain intensity in children with acute abdominal pain or an extremity fracture.

Aim 2: To compare the rate of acute (<2 hours) adverse events, including cardiopulmonary adverse events, associated with IV sub-dissociative ketamine and IV morphine. The investigators hypothesize that there is a smaller proportion of cardiopulmonary adverse events associated with IV sub-dissociative ketamine compared to IV morphine.

Aim 3: To determine the relationship between ketamine and long-term sequelae of acute pain. The investigators hypothesize that children who receive ketamine will have better levels of pain-related function during the first week following ED presentation and will have greater odds of experiencing more favorable post-traumatic stress, anxiety and depression outcomes 1-6 months after ED presentation compared to children who received IV morphine.

• Study Type: Interventional
• Enrollment (Estimated): 1010
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amy L Drendel, DO, MS; Email: adrendel@mcw.edu
• Study Contact Backup: Name: Daniel S Tsze, MD, MPH; Phone Number: 917-375-2647; Email: dst2141@cumc.columbia.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
      • Contact: Deborah Liu, MD; Phone Number: 323-660-2450; Email: deliu@chla.usc.edu
    • Sacramento, California, United States, 95817
      • UC Davis Children's Hospital
      • Contact: Leah Tzimenatos, MD; Phone Number: 800-282-3284; Email: lstzimenatos@ucdavis.edu
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Children's Hospital
      • Contact: Amy Thompson, MD, MSCR; Phone Number: 302-651-4200; Email: amy.thompson@nemours.org
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Arthur M. Blank Hospital
      • Contact: Becky Burger, MD; Phone Number: 404-785-5437; Email: beckyburger@emory.edu
      • Contact: Claudia R Morris; Email: claudia.r.morris@emory.edu
  • New York
    • New York, New York, United States, 10032
      • NewYork Presbyterian Morgan Stanley Children's Hospital
      • Contact: Daniel S Tsze, MD, MPH; Phone Number: 212-305-6628; Email: dst2141@cumc.columbia.edu
      • Contact: Raquel Shrager; Email: rs3823@cumc.columbia.edu
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
      • Contact: Bob Hickey, MD; Email: robert.hickey@chp.edu
      • Contact: Maren Lunoe, MD; Phone Number: 412-692-5325; Email: maren.lunoe@chp.edu
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
      • Contact: Eileen Klein, MD, MPH; Phone Number: 206-987-8811; Email: eileen.klein@seattlechildrens.org
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Wisconsin
      • Contact: Amy L Drendel, DO, MS; Phone Number: 877-266-8989; Email: adrendel@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Abdominal pain or isolated long-bone extremity fracture (suspected or proven)
2. Self-reported pain score of ≥ 6/10
3. Requires IV morphine for analgesia as determined by the treating physician

Exclusion Criteria:

1. Weight > 82.4 kg
2. Known allergy/contraindication to morphine or ketamine
3. Antecedent receipt of ketamine related to presenting complaint
4. Inability to use self-report measures of pain or questionnaires
5. Chronic disease associated with pain
6. Chronic pain condition requiring use of opioids as outpatient
7. Hemodynamic instability or critical illness per treating physician
8. Altered mental state (e.g., GCS , 14 or clinical intoxication)
9. Known history of schizophrenia, liver or kidney problems, or osteogenesis imperfecta
10. Concern for open fracture, neurovascular compromise, or compartment syndrome
11. Injuries in addition to the extremity injury (e.g., head, neck, abdomen)
12. Known or reported pregnancy
13. Does not speak English or Spanish
14. Patient previously enrolled in this study
15. Wards of state, foster children, or children in custody

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: Sub-dissociative ketamine; 0.25 mg/kg, maximum dose 25 mg	Drug: Ketamine hydrochloride; Sub-dissociative ketamine, IV
Active Comparator: Morphine; 0.1 mg/kg, maximum dose 8 mg	Drug: Morphine sulphate; Morphine, IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	Self-reported pain intensity measured using the Verbal Numerical Rating Scale (VNRS). Scored from 0 to 10. A higher score indicates a worse outcome.	Up to 120 minutes after completion of study drug administration or until a terminal event occurs
Adverse events, acute	Examples of adverse events include, but are not limited to, cardiopulmonary adverse events (e.g., hypoxia, respiratory depression, hypotension); opioid-related adverse events; and adverse events as measured using the Side Effects Rating Scale of Dissociative Anesthetics (SERSDA).	Up to 120 minutes after completion of study drug administration or until a terminal event occurs
Pain-related function	Pain intensity and related functional limitations due to pain, measured using the Parents' Postoperative Pain Measure (PPPM). Scored from 0 to 10. A higher score indicates a worse outcome.	Days 1, 2,3, 7 and 30 after discharge.
Traumatic stress, primary assessment	Stress related to the pain experienced measured using the Child Stress Disorder Checklist (CSDC-SF). Scored from 0 to 8. A higher score indicates a worse outcome.	Baseline (at time of enrollment) and days 7, 30, 90 and 180 after discharge.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Receipt of rescue analgesia	Number of participants who received a rescue analgesic administered.	Up to 120 minutes after completion of study drug administration or until a terminal event occurs
Desire for same analgesic	Number of participants who would want the same analgesic (i.e., study medication) again in the future.	At 240 minutes after completion of study drug administration or when a terminal event occurs
Depth of sedation	Depth of sedation measured using the University of Michigan Sedation Scale (UMSS). Scored from 0 to 4. 0 is deepest level of sedation (unarousable), 4 is awake and alert.	Up to 120 minutes after completion of study drug administration or until a terminal event occurs
Analgesic/opioid use after discharge	Name, dose and duration of analgesics and/or opioids used to calculate total days of use during the elapsed time since last assessment	Days 1, 2, 3, 7, 30, 90, and 180 after discharge
Missed school or work	Days of missed school or work related to the chief complaint.	Day 7, 30, 90, 180 after discharge
Return visit	Number of return visits related to the chief complaint, which can include (but not limited to) return visits to the emergency department or primary care physician	Day 7, 30, 90, 180 after discharge
Anxiety	General Anxiety Disorder-7 (GAD-7). Scored from 0 to 21. A higher score indicates a worse outcome.	Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge
Depression	Patient-Reported Outcomes Measurement Information System (PROMIS). Scored from 8 to 40. A higher score indicates a worse outcome.	Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge
Substance use	National Institute on Drug Abuse (NIDA) modified assist tool. Scored from 0 to 360. A higher score indicates a worse outcome.	Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global satisfaction	Global satisfaction with analgesia measured using the Patient Global Impression of Change (PGIC) score. Scored from 1 to 7. A higher score indicates a worse outcome.	Up to 120 minutes after completion of study drug administration or until a terminal event occurs
Opioid use/misuse	Name, dose and duration of opioids used to calculate total days of use during the elapsed time since last assessment and indication for use	Days 30, 90, and 180 after discharge
Pain catastrophizing	Assessment of heightened negative cognitive and affective pain responses in children. Measured using the Pain Catastrophizing Scale (PCS) for Children. Scored from 0 to 4. A higher score indicates more catastrophizing.	Baseline (at time of enrollment) and day 7 after discharge.
Pain interference	How much pain interferes with daily activities measured using the Brief Pain Inventory (BPI) Pain Interference. Scored from 0 to 10. A higher score indicates a worse outcome.	Day 7 after discharge
Physical functioning	Health related quality of life measured using the Pediatric Quality of Life (PedsQL) inventory. Scored from 0 to 100. A higher score indicates a better health-related quality of life.	Baseline (at time of enrollment) and day 7 after discharge
Sleep	Impact of pain on sleep measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Sleep Disturbance 8a + sleep duration. Scored from 8 to 40. A higher score indicates a worse outcome.	Baseline (at time of enrollment) and day 7 after discharge
Traumatic stress, secondary assessment	University of California Los Angeles Post-Traumatic Stress Disorder (UCLA PTSD). Scored from 0 to 108. A higher score indicates a worse outcome.	Days 7, 30, 90, and 180 after discharge.
Parent/Guardian/Caregiver Pain Catastrophizing	Pain Catastrophizing Scale (PCS) for Parents. Scored from 0 to 52. A higher score indicates a worse outcome.	Day 180 after discharge
Parent/Guardian/Caregiver Pain Depression	Patient Health Questionnaire-2 (PHQ-2). Scored from 0 to 6. If the score is 3 or greater, major depressive disorder is likely.	Day 180 after discharge.
Parent/Guardian/Caregiver Pain Anxiety	Generalized Anxiety Disorder 2-item (GAD-2). Scored from 0 to 6. A higher score indicates a worse outcome.	Day 180 after discharge
Parent/Guardian/Caregiver Pain Quality of Life	World Health Organization Quality of Life-2 item (WHOQOL-2). Scored from 2 to 10. A higher score indicates a better outcome.	Day 180 after discharge

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Daniel S Tsze, MD, MPH, Columbia University; Principal Investigator: Amy L Drendel, DO, MS, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: February 17, 2025
• First Posted (Actual): February 19, 2025

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Children; Analgesia; Pediatric; Ketamine; Morphine; Emergency department; Fracture; Abdominal pain; Emergency care; Post-traumatic stress; Emergency medicine; Opioid-sparing; Sub-dissociative
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Pathologic Processes; Disease Attributes; Signs and Symptoms, Digestive; Behavioral Symptoms; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Pain; Abdominal Pain; Anxiety Disorders; Emergencies; Fractures, Bone; Depression; Agnosia; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Morphine; Ketamine
• Other Study ID Numbers: AAAV7115; U01HD116253 (U.S. NIH Grant/Contract); IRB00181652 (Other Identifier: University of Utah Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Consistent with the HEAL Public Access and Data Sharing Policy, one of our goals is to assure rapid data sharing. The de-identified Underlying Primary Data will only be shared when confirmed to be de-identified by the EMSC Data Center (EDC), according to the standards set forth in the Department of Health and Human Services Regulations for the Protection of Human Subjects, to ensure that the identities of research participants cannot be readily ascertained from the data. Underlying Primary Data will also be stripped of identifiers according to the HIPAA Privacy Rule. The EDC is familiar with these processes given their vast experience with data management. The de-identified data will be made available at the conclusion of the project period, and any manuscripts published before the end of the project period will have accompanying release of relevant deidentified data at the time of the manuscript publications.
• IPD Sharing Time Frame: The de-identified data will be made available at the conclusion of the project period (currently August 2029, but may be subject to an extension), and any manuscripts published before the end of the project period will have accompanying release of relevant deidentified data at the time of the manuscript publications. The investigators recognize that the NIH may require a particular repository to be used, but otherwise, the investigators intend to submit the end-of-study data to NICHD DASH, in which case the end date of access would be subject to NICHD DASH policies.
• IPD Sharing Access Criteria: Because it is a condition of the NIH for newly funded studies to make data publicly available, the investigators are not sure what the future use may be. For our intended repository (NICHD DASH), applicants to receive the releasable data are required to abide by the User Agreement. The investigators note that if there are published manuscripts before the project period ends, minimal de-identified data would be made available to support the manuscript's reproducibility and enable further work. Such pre-trial-completion releases of deidentified data are to comply with Helping to End Addiction Long-term (HEAL) policies on data availability. The end-of-study deidentified data will be findable and available through the NICHD DASH repository's search functionality. The investigators will also note where the data are available in the primary study manuscript; as required for HEAL Initiative®-funded trials, the publications from this trial will be available as open access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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