Clinical trial NCT06835504: Morphine or Ketamine for Analgesia
Official title: Efficacy of Intravenous Sub-Dissociative Ketamine Versus Intravenous Morphine in Children with Acute Pain
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Abdominal Pain
Isolated Extremity Fracture
Pain
Pediatrics
Keywords: Ketamine
Morphine
Pediatric
Children
Sub-dissociative
Opioid-sparing
Emergency medicine
Emergency care
Emergency department
Post-traumatic stress
Anxiety
Depression
Abdominal pain
Fracture
Analgesia
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2025-02-19
Enrollment: 1010
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non-inferiority trial design
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pain intensity
timeFrame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs
measure: Adverse events, acute
timeFrame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs
measure: Pain-related function
timeFrame: Days 1, 2,3, 7 and 30 after discharge.
measure: Traumatic stress, primary assessment
timeFrame: Baseline (at time of enrollment) and days 7, 30, 90 and 180 after discharge.
Secondary outcomes:
measure: Receipt of rescue analgesia
timeFrame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs
measure: Desire for same analgesic
timeFrame: At 240 minutes after completion of study drug administration or when a terminal event occurs
measure: Depth of sedation
timeFrame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs
measure: Analgesic/opioid use after discharge
timeFrame: Days 1, 2, 3, 7, 30, 90, and 180 after discharge
measure: Missed school or work
timeFrame: Day 7, 30, 90, 180 after discharge
measure: Return visit
timeFrame: Day 7, 30, 90, 180 after discharge
measure: Anxiety
timeFrame: Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge
measure: Depression
timeFrame: Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge
measure: Substance use
timeFrame: Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge
Other outcomes:
measure: Global satisfaction
timeFrame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs
measure: Opioid use/misuse
timeFrame: Days 30, 90, and 180 after discharge
measure: Pain catastrophizing
timeFrame: Baseline (at time of enrollment) and day 7 after discharge.
measure: Pain interference
timeFrame: Day 7 after discharge
measure: Physical functioning
timeFrame: Baseline (at time of enrollment) and day 7 after discharge
measure: Sleep
timeFrame: Baseline (at time of enrollment) and day 7 after discharge
measure: Traumatic stress, secondary assessment
timeFrame: Days 7, 30, 90, and 180 after discharge.
measure: Parent/Guardian/Caregiver Pain Catastrophizing
timeFrame: Day 180 after discharge
measure: Parent/Guardian/Caregiver Pain Depression
timeFrame: Day 180 after discharge.
measure: Parent/Guardian/Caregiver Pain Anxiety
timeFrame: Day 180 after discharge
measure: Parent/Guardian/Caregiver Pain Quality of Life
timeFrame: Day 180 after discharge
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Sacramento
country: United States
facility: UC Davis Children's Hospital
state: California
city: Wilmington
country: United States
facility: Nemours Children's Hospital
state: Delaware
city: Atlanta
country: United States
facility: Arthur M. Blank Hospital
state: Georgia
city: New York
country: United States
facility: NewYork Presbyterian Morgan Stanley Children's Hospital
state: New York
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Wisconsin
state: Wisconsin
Study officials:
affiliation: Columbia University
name: Daniel S Tsze, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Amy L Drendel, DO, MS
role: PRINCIPAL_INVESTIGATOR
References: