NCT06835504

Brief Summary

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.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,010

participants targeted

Target at P75+ for phase_3

Timeline
43mo left

Started May 2026

Typical duration for phase_3

Geographic Reach
1 country

8 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 16, 2024

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 19, 2025

Completed
1.2 years until next milestone

Study Start

First participant enrolled

May 1, 2026

Expected
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2029

6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2029

Last Updated

January 26, 2026

Status Verified

January 1, 2026

Enrollment Period

3 years

First QC Date

December 16, 2024

Last Update Submit

January 23, 2026

Conditions

Keywords

KetamineMorphinePediatricChildrenSub-dissociativeOpioid-sparingEmergency medicineEmergency careEmergency departmentPost-traumatic stressAnxietyDepressionAbdominal painFractureAnalgesia

Outcome Measures

Primary Outcomes (4)

  • 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 Outcomes (9)

  • Receipt of rescue analgesia

    Up to 120 minutes after completion of study drug administration or until a terminal event occurs

  • Desire for same analgesic

    At 240 minutes after completion of study drug administration or when a terminal event occurs

  • Depth of sedation

    Up to 120 minutes after completion of study drug administration or until a terminal event occurs

  • Analgesic/opioid use after discharge

    Days 1, 2, 3, 7, 30, 90, and 180 after discharge

  • Missed school or work

    Day 7, 30, 90, 180 after discharge

  • +4 more secondary outcomes

Other Outcomes (11)

  • Global satisfaction

    Up to 120 minutes after completion of study drug administration or until a terminal event occurs

  • Opioid use/misuse

    Days 30, 90, and 180 after discharge

  • Pain catastrophizing

    Baseline (at time of enrollment) and day 7 after discharge.

  • +8 more other outcomes

Study Arms (2)

Sub-dissociative ketamine

EXPERIMENTAL

0.25 mg/kg, maximum dose 25 mg

Drug: Ketamine hydrochloride

Morphine

ACTIVE COMPARATOR

0.1 mg/kg, maximum dose 8 mg

Drug: Morphine sulphate

Interventions

Sub-dissociative ketamine, IV

Sub-dissociative ketamine

Morphine, IV

Morphine

Eligibility Criteria

Age6 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

UC Davis Children's Hospital

Sacramento, California, 95817, United States

Location

Nemours Children's Hospital

Wilmington, Delaware, 19803, United States

Location

Arthur M. Blank Hospital

Atlanta, Georgia, 30329, United States

Location

NewYork Presbyterian Morgan Stanley Children's Hospital

New York, New York, 10032, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Abdominal PainPainEmergenciesAnxiety DisordersDepressionFractures, BoneAgnosia

Interventions

KetamineMorphine

Condition Hierarchy (Ancestors)

Neurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsSigns and Symptoms, DigestiveDisease AttributesPathologic ProcessesMental DisordersBehavioral SymptomsBehaviorWounds and InjuriesPerceptual DisordersNeurobehavioral ManifestationsNervous System Diseases

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsMorphine DerivativesMorphinansOpiate AlkaloidsAlkaloidsHeterocyclic CompoundsHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic Compounds

Study Officials

  • Daniel S Tsze, MD, MPH

    Columbia University

    PRINCIPAL INVESTIGATOR
  • Amy L Drendel, DO, MS

    Medical College of Wisconsin

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel S Tsze, MD, MPH

CONTACT

Amy L Drendel, DO, MS

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Non-inferiority trial design
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Pediatrics in Emergency Medicine

Study Record Dates

First Submitted

December 16, 2024

First Posted

February 19, 2025

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

April 30, 2029

Study Completion (Estimated)

October 31, 2029

Last Updated

January 26, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
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.
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.
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