Comparison of Ketorolac at 3 Doses in Children With Acute Pain: Protocol for A Randomized Controlled Trial
Bibliographic record
Abstract
BACKGROUND: Intravenous ketorolac is a potent nonopioid analgesic commonly used to treat vigorous pain in children and adults. Despite its widespread use in pediatric emergency settings, ketorolac dosing in children remains "off-label," with limited high-quality evidence to guide practice. Pharmacokinetic differences between children and adults suggest that lower ceiling doses adopted from adult practice may lead to suboptimal analgesia in pediatric populations. Inconsistent ketorolac dosing practices across centers reflect substantial clinical uncertainty. Amid efforts to reduce opioid use and provide effective nonopioid alternatives, rigorous pediatric trials evaluating ketorolac dosing are urgently needed. OBJECTIVE: The primary objective is to determine whether 2 lower-dose intravenous ketorolac strategies (0.25 mg/kg-30 mg or 0.5 mg/kg-10 mg) are noninferior to the standard dosing regimen (0.5 mg/kg-30 mg) in reducing mean pain scores at 60 minutes postadministration in children aged 6-17 years presenting with vigorous pain. The secondary hypothesis is that ketorolac 0.5 mg/kg up to 10 mg will be superior to 0.25 mg/kg up to 30 mg by at least the minimally important difference of 2.0 points on the verbal Numerical Rating Scale (vNRS). METHODS: The KETODOSE trial is a single-center, randomized, double-blind, double-dummy, noninferiority trial conducted at McMaster Children's Hospital. Eligible participants aged 6 to <18 years with vigorous pain (vNRS >4) are randomized in a 1:1:1 ratio to standard dosing or one of 2 low-dose ketorolac regimens. Study drugs are administered via intravenous push over 5 minutes. Pain scores are assessed at baseline, 30, 60, 90, and 120 minutes. The primary endpoint is the mean change in vNRS score at 60 minutes. Secondary outcomes include pain scores at other time points, time to effective analgesia, rescue analgesia requirements, opioid consumption, and adverse events. Caregiver perceptions regarding analgesic use are evaluated using a mixed-methods semistructured survey. A sample size of 180 participants (60 per group) provides 80% power to detect noninferiority within a margin of 1.0 on the vNRS, assuming an SD of 1.5. Intention-to-treat and per-protocol analyses will be performed. RESULTS: Recruitment is ongoing. Final analyses will be performed once follow-up is completed for all participants. Results will be disseminated through peer-reviewed publications, conference presentations, caregiver- and clinician-facing educational tools, and national knowledge mobilization networks. CONCLUSIONS: The KETODOSE trial will provide urgently needed evidence to guide ketorolac dosing for acute pain in children. If lower-dose regimens are shown to be noninferior to standard dosing, this may promote safer prescribing practices, reduce adverse events, and support efforts to minimize pediatric opioid use, thereby improving acute pain management in pediatric emergency care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05641363; https://clinicaltrials.gov/study/NCT05641363. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/76554.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.047 | 0.048 |
| Meta-epidemiology (narrow) | 0.009 | 0.004 |
| Meta-epidemiology (broad) | 0.017 | 0.007 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.004 | 0.005 |
| Scholarly communication | 0.006 | 0.005 |
| Open science | 0.005 | 0.002 |
| Research integrity | 0.010 | 0.010 |
| Insufficient payload (model declined to judge) | 0.078 | 0.012 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".