Morphine or Ketamine for Analgesia

Official title

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

Overview

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.

Interventions

• Drug Ketamine hydrochloride
  Sub-dissociative ketamine, IV
• Drug Morphine sulphate
  Morphine, IV

Primary outcome measures

• Pain intensity [Time frame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs]
• Adverse events, acute [Time frame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs]
• Pain-related function [Time frame: Days 1, 2,3, 7 and 30 after discharge.]
• Traumatic stress, primary assessment [Time frame: Baseline (at time of enrollment) and days 7, 30, 90 and 180 after discharge.]

Secondary outcome measures (9)

• Receipt of rescue analgesia [Time frame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs]
• Desire for same analgesic [Time frame: At 240 minutes after completion of study drug administration or when a terminal event occurs]
• Depth of sedation [Time frame: Up to 120 minutes after completion of study drug administration or until a terminal event occurs]
• Analgesic/opioid use after discharge [Time frame: Days 1, 2, 3, 7, 30, 90, and 180 after discharge]
• Missed school or work [Time frame: Day 7, 30, 90, 180 after discharge]
• Return visit [Time frame: Day 7, 30, 90, 180 after discharge]
• Anxiety [Time frame: Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge]
• Depression [Time frame: Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge]
• Substance use [Time frame: Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 8 centers

• Children's Hospital Los Angeles — Los Angeles
• UC Davis Children's Hospital — Sacramento
• Nemours Children's Hospital — Wilmington
• Arthur M. Blank Hospital — Atlanta
• NewYork Presbyterian Morgan Stanley Children's Hospital — New York
• UPMC Children's Hospital of Pittsburgh — Pittsburgh
• Seattle Children's Hospital — Seattle
• Children's Wisconsin — Milwaukee

Identifiers

NCT: NCT06835504 · AAAV7115 · U01HD116253 · IRB00181652

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗