Intranasal Dexmedetomidine Dose-finding Study
Condition: Laceration Repair
MeSH terms: Lacerations
Study type: Interventional
Phase: Phase 2

Summary: 
      The most common injury prompting an emergency department (ED) visit in children is a cut
      (laceration) that requires repair using stitches or skin glue. Despite anesthetic (freezing),
      laceration repair is often very distressful because in young children, most occur on the
      face. There is currently no effective drug to relieve the distress of laceration repair in
      children. The goal is to find a safe and effective drug to reduce distress in children
      undergoing laceration repair. Dexmedetomidine is a new drug that safely provides mild
      sedation and can be given as a painless nasal spray. Intranasal dexmedetomidine (IND) has
      been shown to reduce distress in children undergoing painful procedures such as dental work
      and intravenous insertion. However, no large study has explored IND for laceration repair. In
      order for research to change the way we care for children, a large study that enrolls
      children across many paediatric EDs needs to be performed. The first step is to conduct a
      smaller study to identify the safest and most effective dose. The proposed study plans to
      enroll 55 children age 1-10 years who require laceration repair.
    

Detailed description: 
      Design: This study will be designed as a phase II single-arm dose-escalation pilot study
      using the continual reassessment method.

      Protocol: Sedation will be measured using the Pediatric Sedation State Scale (PSSS), an
      instrument validated for video scoring of children undergoing painful procedures. The PSSS is
      scored from 0 (dangerously sedated) to 5 (least sedated) easily by non-medical personnel and
      assesses over sedation and under sedation. Adequate sedation is a score of 2 or 3.
      Participants will be consecutively assigned to increasing doses of IND from 1-4 mcg/kg based
      on the continual reassessment method. Participants will be assigned to doses of IND from 1-4
      mcg/kg, increasing in whole number increments. Initially three participants will receive
      1mcg/kg and the number of participants at each dose of IND will be recorded. Data from these
      participants will be used to update a Bayesian model for the dose-response curve for all
      three categories of sedation. The following three participants will be assigned the dose with
      the highest posterior probability of an efficacy close to 0.8. This balances the need to
      determine the most efficacious dose but prevents an excessive number of over-sedations. For
      the Bayesian dose response model, a determination will be made as to the overall score
      category for each participant ("adequate", "over", or "under sedated" based on the PSSS). To
      be scored as "adequate", a participant must have a PSSS score of 2 or 3 for at least 90% of
      observations from initial positioning to tying of the last suture. If a participant does not
      retain a PSSS score of 2 or 3 for at least 90% of the observations, they will be categorized
      as either over or under-sedated, if the majority of the remaining PSSS scores are 0 or 1 or 4
      or 5, respectively. Furthermore, if the participant remains awake, but not distressed during
      the procedure, they will be scored as a 2 based on the PSSS. However, for the purposes of the
      Bayesian dose response model, they will be scored as "under sedated" to avoid concluding that
      a lower dose of IND is effective based on the outcomes for participants that did not require
      sedation. Finally, participants who are noncompliant with IND will be categorized as an
      over-sedation as it is assumed that this dose was not well tolerated by the participant and
      dose escalation should be avoided. Data will be reviewed after each dose increment by a data
      safety monitoring board, who will confirm it is safe to escalate. Permissible
      co-interventions include topical and subcutaneous anesthetic, oral or IV analgesics,
      non-pharmacologic strategies for pain and distress.

      Screening and Enrollment: Participants will be consecutively screened for eligibility during
      the hours of study recruitment.

      Sample Size: This was calculated using the Bayesian continual reassessment method (20). Based
      on an adverse event rate of 10%, 4 dosing levels, an odds ratio for the effect size of 1.8,
      and a phase II trial accuracy level of 60%, an estimated a sample size of 55 participants was
      calculated.
    

Intervention name(s): Dexmedetomidine
Intervention type(s): Drug
Intervention description(s): Intranasal dexmedetomidine
Intervention MeSH terms: Dexmedetomidine
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Dose-escalation pilot study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment