Although this trial is still recruiting, we have been able to meet several pre-specified deliverables of the AMOSO grant and enable the IFPOC to determine the project’s success. Seven peer-reviewed manuscripts have been published detailing trial protocol, methods, stopping rules, and statistical analysis. This will enable researchers and knowledge users to easily access the content so they can replicate our methods for other painful conditions and procedures. We used the results from our pilot work on IN ketamine and systematic reviews to create a practice parameter for the safe and effective use of IN sedatives by healthcare providers. It specifies the volume, angle of administration, and how to position patients for optimal drug delivery, as well as safe monitoring of sedated children. The parameter has been disseminated across Canada through Departmental Grand Rounds and Continuing Medical Education engagements.

Objectives
The trial’s objective is to determine if IN Ketodex (ketamine plus dexmedetomidine) is non-inferior to IV ketamine in children 4-17 years who require procedural sedation for reduction of an orthopedic injury with respect to adequacy of sedation.

Methodology
This is a randomized, blinded, multicentre, adaptive trial enrolling 410 children across 6 Canadian paediatric emergency departments (EDs). A dose-finding analysis will be performed once 150 participants have been enrolled. The primary outcome is the adequacy of sedation based on the Paediatric Sedation State Scale (PSSS), adverse effects, tolerance of IN sprays, and delayed maladaptive behaviors. Results will be supported by a health economic analysis.

Results
A total of 86 participants have been recruited. Of these, all but two completed the primary outcome and 95% completed all follow-up tasks. Consent rates are roughly 70% across enrolling sites. No participants have been withdrawn. One participant experienced a transient self-resolving oxygen desaturation but there have been no serious adverse events. Several manuscripts have been published detailing trial methods, stopping rules, and statistical analysis. Training of highly qualified personnel (HQP) has been done and include a project manager, knowledge translation specialist, methodologist skilled in adaptive trial design and analysis, and qualitative design specialist. For providers, this trial has led to the development of standard operating procedures for safe and effective administration of intranasal sedative agents to children in the emergency department.

Conclusions
The Ketodex trial is currently enrolling. Seed funding from AMOSO has allowed us to procure additional funds to expand recruitment sites and we anticipate completion in December 2024.

Challenges
These include several drug shortages lasting ~1 year, a 2-year pandemic hiatus, and ongoing post-pandemic research nurse shortages.

1. A Heath, D Rios, E Pullenayegum, P Pechlivanoglou, M Offringa, M Yaskina, R Watts, S Rimmer, TP Klassen, K Coriolano, N Poonai. The intranasal dexmedetomidine plus ketamine for procedural sedation in children, adaptive randomized controlled non-inferiority multicenter trial (Ketodex): a statistical analysis plan. Trials. 2021. DOI: doi.org/10.1186/s13063-020-04946-3
2. N Poonai, K Coriolano, TP Klassen et al. Adaptive randomised controlled non-inferiority multicentre trial (the Ketodex trial) on intranasal dexmedetomidine plus ketamine for procedural sedation in children: a study protocol. BMJ Open. 2020;10:e041319
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5. N Poonai, J Spohn, B Vandermeer, S Ali, M Bhatt, S Hendrikx, E Trottier, V Sabhaney, A Shah, G Joubert, L Hartling. Intranasal dexmedetomidiene for procedures associated with pain or anxiety in children: a systematic review and meta-analysis. Pediatrics. 2020;145(1):e2019162
6. N Poonai, K Canton, S Ali, S Hendrikx, A Shah, M Miller, G Joubert, M Rieder, L Hartling. Intranasal ketamine for procedural sedation and analgesia in children: a systematic review. PLoS One. 2017;12(3):e0173253
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