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| ID | Type | Description | Link |
|---|---|---|---|
| U01HD116253 | U.S. NIH Grant/Contract | View source | |
| IRB00181652 | Other Identifier | University of Utah Institutional Review Board |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sub-dissociative ketamine | Experimental | 0.25 mg/kg, maximum dose 25 mg |
|
| Morphine | Active Comparator | 0.1 mg/kg, maximum dose 8 mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine hydrochloride | Drug | Sub-dissociative ketamine, IV |
| |
| 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. |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daniel S Tsze, MD, MPH | Contact | 917-375-2647 | dst2141@cumc.columbia.edu | |
| Amy L Drendel, DO, MS | Contact | adrendel@mcw.edu |
| Name | Affiliation | Role |
|---|---|---|
| Daniel S Tsze, MD, MPH | Columbia University | Principal Investigator |
| Amy L Drendel, DO, MS | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
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.
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.
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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| ID | Term |
|---|---|
| D015746 | Abdominal Pain |
| D010146 | Pain |
| D004630 | Emergencies |
| D001008 | Anxiety Disorders |
| D003863 | Depression |
| D050723 | Fractures, Bone |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012817 | Signs and Symptoms, Digestive |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| D009020 | Morphine |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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Non-inferiority trial design
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| Morphine sulphate |
| Drug |
Morphine, IV |
|
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 |
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 |
| UC Davis Children's Hospital | Sacramento | California | 95817 | United States |
|
| Nemours Children's Hospital | Wilmington | Delaware | 19803 | United States |
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| Arthur M. Blank Hospital | Atlanta | Georgia | 30329 | United States |
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| NewYork Presbyterian Morgan Stanley Children's Hospital | New York | New York | 10032 | United States |
|
| UPMC Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15224 | United States |
|
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
|
| Children's Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D014947 | Wounds and Injuries |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |