Clinical trial NCT04027829: Pharmacokinetics-pharmacodynamics and Safety of Dexmedetomidine in Children
Official title: Pharmacokinetic-pharmacodynamic Analysis for Dosing Strategy and Evaluation of Safety and Efficacy of Dexmedetomidine in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intensive Care Unit
Postoperative Care
Keywords: dexmedetomidine
pediatric
sedation
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Food and Drug Safety, Korea
First posted: 2019-07-22
Enrollment: 13
Sex: ALL
Minimum age (years): 7
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Dexmedetomidine infusion at intensive care unit
Primary purpose: SUPPORTIVE_CARE

Brief summary: This study evaluates pharmacokinetics and pharmacodynamics of dexmedetomidine for children under sedation at intensive care unit after surgery. Patients will receive dexmedetomidine intravenously for 50 minutes after surgery as as sedation drug.

Detailed description: Dexmedetomidine, an alpha-2 adrenergic agonist, is being effectively used for procedural sedation or sedation at intensive care unit. However, the safety and efficacy profile are not yet established for children. Although there have been some studies regrading it, still there is no public guideline, therefore making it difficult to use dexmedetomidine in children.

Eligibility criteria: Inclusion Criteria:

* Pediatric patients planned to undergo mechanical ventilation at intensive care unit after surgery
* Pediatric patients planned to be extubated within 4 hours after surgery for neurological examination
* Patients whose parent of legal guardian agreed to enroll in the study after having enough time to review the complete explanation about the study.

Exclusion Criteria:

* History of hypersensitivity to any drugs including dexmedetomidine.
* Underlying cardiovascular/circulatory disease
* Underlying liver / kidney disease
* Patients under hemodialysis
* Obesity of BMI \> 35
* Patients planned to receive patient-controlled analgesia including opioids
* Patients whose parent or legal guardian declined to enroll in the study
* Other conditions deemed unsuitable for the study

Primary outcomes:
measure: Plasma concentration of dexmedetomidine
timeFrame: From start of dexmedetomidine infusion to 480 minutes after end of dexmedetomidine infusion
measure: Bispectral index
timeFrame: From start of dexmedetomidine infusion to 480 minutes after end of dexmedetomidine infusion
measure: University of Michigan Sedation Scale
timeFrame: From start of dexmedetomidine infusion to 480 minutes after end of dexmedetomidine infusion
Secondary outcomes:
measure: Incidence of arrhythmia
timeFrame: From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
measure: Non-invasive blood pressure
timeFrame: From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
measure: Incidence of desaturation
timeFrame: From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
measure: Respiratory rate
timeFrame: From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
measure: Incidence of nausea
timeFrame: From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
measure: Incidence of vomiting
timeFrame: From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongro Gu
Study officials:
affiliation: Seoul National University Hospital
name: Hee-Soo Kim, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med. 2007 Mar;8(2):115-31. doi: 10.1097/01.PCC.0000257100.31779.41.
citation: Su F, Hammer GB. Dexmedetomidine: pediatric pharmacology, clinical uses and safety. Expert Opin Drug Saf. 2011 Jan;10(1):55-66. doi: 10.1517/14740338.2010.512609. Epub 2010 Aug 18.
citation: Reiter PD, Pietras M, Dobyns EL. Prolonged dexmedetomidine infusions in critically ill infants and children. Indian Pediatr. 2009 Sep;46(9):767-73. Epub 2009 Apr 1.
citation: Banasch HL, Dersch-Mills DA, Boulter LL, Gilfoyle E. Dexmedetomidine Use in a Pediatric Intensive Care Unit: A Retrospective Cohort Study. Ann Pharmacother. 2018 Feb;52(2):133-139. doi: 10.1177/1060028017734560. Epub 2017 Sep 27.
citation: Sulton C, McCracken C, Simon HK, Hebbar K, Reynolds J, Cravero J, Mallory M, Kamat P. Pediatric Procedural Sedation Using Dexmedetomidine: A Report From the Pediatric Sedation Research Consortium. Hosp Pediatr. 2016 Sep;6(9):536-44. doi: 10.1542/hpeds.2015-0280. Epub 2016 Aug 11.
citation: Plambech MZ, Afshari A. Dexmedetomidine in the pediatric population: a review. Minerva Anestesiol. 2015 Mar;81(3):320-32. Epub 2014 May 14.
citation: Kim HS, Byon HJ, Kim JE, Park YH, Lee JH, Kim JT. Appropriate dose of dexmedetomidine for the prevention of emergence agitation after desflurane anesthesia for tonsillectomy or adenoidectomy in children: up and down sequential allocation. BMC Anesthesiol. 2015 May 27;15:79. doi: 10.1186/s12871-015-0059-z.
citation: Mahmoud M, Mason KP. Dexmedetomidine: review, update, and future considerations of paediatric perioperative and periprocedural applications and limitations. Br J Anaesth. 2015 Aug;115(2):171-82. doi: 10.1093/bja/aev226.
citation: Tobias JD, Berkenbosch JW. Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J. 2004 May;97(5):451-5. doi: 10.1097/00007611-200405000-00007.
citation: Chrysostomou C, Sanchez De Toledo J, Avolio T, Motoa MV, Berry D, Morell VO, Orr R, Munoz R. Dexmedetomidine use in a pediatric cardiac intensive care unit: can we use it in infants after cardiac surgery? Pediatr Crit Care Med. 2009 Nov;10(6):654-60. doi: 10.1097/PCC.0b013e3181a00b7a.
citation: Walker J, Maccallum M, Fischer C, Kopcha R, Saylors R, McCall J. Sedation using dexmedetomidine in pediatric burn patients. J Burn Care Res. 2006 Mar-Apr;27(2):206-10. doi: 10.1097/01.BCR.0000200910.76019.CF.
citation: Koroglu A, Demirbilek S, Teksan H, Sagir O, But AK, Ersoy MO. Sedative, haemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: preliminary results. Br J Anaesth. 2005 Jun;94(6):821-4. doi: 10.1093/bja/aei119. Epub 2005 Mar 11.
citation: Berkenbosch JW, Wankum PC, Tobias JD. Prospective evaluation of dexmedetomidine for noninvasive procedural sedation in children. Pediatr Crit Care Med. 2005 Jul;6(4):435-9; quiz 440. doi: 10.1097/01.PCC.0000163680.50087.93.
citation: Chrysostomou C, Schulman SR, Herrera Castellanos M, Cofer BE, Mitra S, da Rocha MG, Wisemandle WA, Gramlich L. A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates. J Pediatr. 2014 Feb;164(2):276-82.e1-3. doi: 10.1016/j.jpeds.2013.10.002. Epub 2013 Nov 14.
citation: Diaz SM, Rodarte A, Foley J, Capparelli EV. Pharmacokinetics of dexmedetomidine in postsurgical pediatric intensive care unit patients: preliminary study. Pediatr Crit Care Med. 2007 Sep;8(5):419-24. doi: 10.1097/01.PCC.0000282046.66773.39.