Condition or disease | Intervention/treatment | Phase |
---|---|---|
Laceration Repair | Drug: Dexmedetomidine | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 55 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | Dose-escalation pilot study |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Blinding of dose levels will not be possible so outcome assessors will be blinded by virtue of being remote from the clinical encounter. Furthermore, video segments will commence immediately after intranasal sprays are given so outcome assessors will not see what volume is administered. Two independent assessors will score each video and an interrater agreement (kappa) will be calculated. |
Primary Purpose: | Treatment |
Official Title: | Intranasal Dexmedetomidine for Laceration Repair in Children: a Dose-finding Study |
Actual Study Start Date : | February 20, 2020 |
Estimated Primary Completion Date : | September 1, 2021 |
Estimated Study Completion Date : | September 1, 2021 |
Arm | Intervention/treatment |
---|---|
Experimental: Dexmedetomidine 1 mcg/kg
Intranasal dexmedetomidine 100 mcg/mL (Precedex, Pfizer) 1 mcg/kg (max 100 mcg or 1 mL).
|
Drug: Dexmedetomidine
Intranasal dexmedetomidine
|
Active Comparator: Dexmedetomidine 2 mcg/kg
Intranasal dexmedetomidine 100 mcg/mL (Precedex, Pfizer) 2 mcg/kg (max 100 mcg or 1 mL).
|
Drug: Dexmedetomidine
Intranasal dexmedetomidine
|
Active Comparator: Dexmedetomidine 3 mcg/kg
Intranasal dexmedetomidine 100 mcg/mL (Precedex, Pfizer) 3 mcg/kg (max 100 mcg or 1 mL).
|
Drug: Dexmedetomidine
Intranasal dexmedetomidine
|
Active Comparator: Dexmedetomidine 4 mcg/kg
Intranasal dexmedetomidine 100 mcg/mL (Precedex, Pfizer) 4 mcg/kg (max 100 mcg or 1 mL).
|
Drug: Dexmedetomidine
Intranasal dexmedetomidine
|
Ages Eligible for Study: | 1 Year to 10 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Naveen Poonai | 5196858500 | naveen.poonai@lhsc.on.ca |
Canada, Ontario | |
London Health Sciences Centre | Recruiting |
London, Ontario, Canada, N6A5W9 | |
Contact: Naveene Poonai, MD 5196945309 naveen.poonai@lhsc.on.ca |
Tracking Information | |||||||
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First Submitted Date ICMJE | May 17, 2019 | ||||||
First Posted Date ICMJE | May 21, 2019 | ||||||
Last Update Posted Date | May 7, 2021 | ||||||
Actual Study Start Date ICMJE | February 20, 2020 | ||||||
Estimated Primary Completion Date | September 1, 2021 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Adequate sedation [ Time Frame: Index visit ] The number of participants with adequate sedation defined as a PSSS or 2 or 3 for the duration of the measurement period (initial positioning to tying of the last suture)
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Original Primary Outcome Measures ICMJE |
Adequate sedation [ Time Frame: Index visit ] Defined as a Dartmouth Operative Conditions Scale (DOCS) from -2 to +2) for the duration of the measurement period ((every 30 seconds from the start of preprocedural positioning to tying of the last suture)
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Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Intranasal Dexmedetomidine Dose-finding Study | ||||||
Official Title ICMJE | Intranasal Dexmedetomidine for Laceration Repair in Children: a Dose-finding Study | ||||||
Brief 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. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Sequential Assignment Intervention Model Description: Dose-escalation pilot study Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Blinding of dose levels will not be possible so outcome assessors will be blinded by virtue of being remote from the clinical encounter. Furthermore, video segments will commence immediately after intranasal sprays are given so outcome assessors will not see what volume is administered. Two independent assessors will score each video and an interrater agreement (kappa) will be calculated. Primary Purpose: Treatment
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Condition ICMJE | Laceration Repair | ||||||
Intervention ICMJE | Drug: Dexmedetomidine
Intranasal dexmedetomidine
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
55 | ||||||
Original Estimated Enrollment ICMJE |
54 | ||||||
Estimated Study Completion Date ICMJE | September 1, 2021 | ||||||
Estimated Primary Completion Date | September 1, 2021 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 1 Year to 10 Years (Child) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Canada | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03957304 | ||||||
Other Study ID Numbers ICMJE | 51384 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Lawson Health Research Institute | ||||||
Study Sponsor ICMJE | Lawson Health Research Institute | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE | Not Provided | ||||||
PRS Account | Lawson Health Research Institute | ||||||
Verification Date | April 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |