Morphine or Ketamine for Analgesia

Phase 3

Not yet recruiting

• Conditions: Abdominal Pain; Isolated Extremity Fracture; Pain; Pediatrics
• Interventions: Drug: Ketamine hydrochloride; Drug: Morphine sulphate

• Registration Number: NCT06835504
• Lead Sponsor: Columbia University

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.

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 Timeline

• Study First Submitted: 2024-12-16
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-17
• Last Update Submitted: 2025-02-17
• Study First Posted: 2025-02-19
• Last Update Posted: 2025-02-19
• Study Start: 2025-09-01
• Primary Completion: 2028-08-31
• Study Completion: 2029-02-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1010

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sub-dissociative ketamine	Ketamine hydrochloride	0.25 mg/kg, maximum dose 25 mg
Morphine	Morphine sulphate	0.1 mg/kg, maximum dose 8 mg

Primary Outcome Measures

Name	Time	Method
Pain intensity	Up to 120 minutes after completion of study drug administration or until a terminal event occurs	Self-reported pain intensity measured using the Verbal Numerical Rating Scale (VNRS). Scored from 0 to 10. A higher score indicates a worse outcome.
Adverse events, acute	Up to 120 minutes after completion of study drug administration or until a terminal event occurs	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).
Pain-related function	Days 1, 2,3, 7 and 30 after discharge.	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.
Traumatic stress, primary assessment	Baseline (at time of enrollment) and days 7, 30, 90 and 180 after discharge.	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.

Secondary Outcome Measures

Name	Time	Method
Receipt of rescue analgesia	Up to 120 minutes after completion of study drug administration or until a terminal event occurs	Number of participants who received a rescue analgesic administered.
Desire for same analgesic	At 240 minutes after completion of study drug administration or when a terminal event occurs	Number of participants who would want the same analgesic (i.e., study medication) again in the future.
Depth of sedation	Up to 120 minutes after completion of study drug administration or until a terminal event occurs	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.
Analgesic/opioid use after discharge	Days 1, 2, 3, 7, 30, 90, and 180 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
Missed school or work	Day 7, 30, 90, 180 after discharge	Days of missed school or work related to the chief complaint.
Return visit	Day 7, 30, 90, 180 after discharge	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
Anxiety	Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge	General Anxiety Disorder-7 (GAD-7). Scored from 0 to 21. A higher score indicates a worse outcome.
Depression	Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge	Patient-Reported Outcomes Measurement Information System (PROMIS). Scored from 8 to 40. A higher score indicates a worse outcome.
Substance use	Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge	National Institute on Drug Abuse (NIDA) modified assist tool. Scored from 0 to 360. A higher score indicates a worse outcome.

Trial Locations

Locations (8)

Arthur M. Blank Hospital; 🇺🇸 Atlanta, Georgia, United States

NewYork Presbyterian Morgan Stanley Children's Hospital; 🇺🇸 New York, New York, United States

UPMC Children's Hospital of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

Children's Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

UC Davis Children's Hospital; 🇺🇸 Sacramento, California, United States

Nemours Children's Hospital; 🇺🇸 Wilmington, Delaware, United States