Pharmacokinetics-pharmacodynamics and Safety of Dexmedetomidine in Children

Intensive Care Unit Clinical Trial

Official title:

Pharmacokinetic-pharmacodynamic Analysis for Dosing Strategy and Evaluation of Safety and Efficacy of Dexmedetomidine in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04027829
• Other study ID #: 1905-188-1037
• Status: Completed
• Phase: Phase 2
• Start date: August 14, 2019
• Est. completion date: November 14, 2019

Study information

• Verified date: April 2020
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: November 14, 2019
• Est. primary completion date: November 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Intensive Care Unit
• Postoperative Care

Intervention

Drug:
• Dexmedetomidine Hydrochloride
Intravenous infusion of dexmedetomidine at the rate of 0.5mcg/kg for 10 min, then 0.5mcg/kg/hr for 50 min.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul	Jongro Gu

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Ministry of Food and Drug Safety, Korea

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (15)

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. — View 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. — View 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. Erratum in: Pediatr Crit Care Med. 2012 May;13(3):373. — View 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. — View Citation

Díaz 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. — View 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. — View 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. Epub 2005 Mar 11. — View 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. Review. — View Citation

Plambech MZ, Afshari A. Dexmedetomidine in the pediatric population: a review. Minerva Anestesiol. 2015 Mar;81(3):320-32. Epub 2014 May 14. Review. — View 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. — View 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. Review. — View 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. — View 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. — View Citation

Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med. 2007 Mar;8(2):115-31. Review. — View 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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentration of dexmedetomidine	Plasma concentration of dexmedetomidine before infusion, 10/30/60 minutes after initiation of infusion, 15/30/60/120/240/480 minutes after end of infusion	From start of dexmedetomidine infusion to 480 minutes after end of dexmedetomidine infusion
Primary	Bispectral index	Bispectral index based on electroencephalogram during patient's stay at intensive care unit (0-100, lower score implies deeper sedation)	From start of dexmedetomidine infusion to 480 minutes after end of dexmedetomidine infusion
Primary	University of Michigan Sedation Scale	University of Michigan Sedation Scale based on observer's inspection during patient's stay at intensive care unit (0-4, higher score implies deeper sedation)	From start of dexmedetomidine infusion to 480 minutes after end of dexmedetomidine infusion
Secondary	Incidence of arrhythmia	Presence of any kind of arrhythmia from electrocardiogram following dexmedetomidine infusion	From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
Secondary	Non-invasive blood pressure	Non-invasive blood pressure in units of mmHg, to examine whether hypertension (increase in blood pressure more than 20% of baseline) or hypotension (decrease in blood pressure more than 20% of baseline) occurs	From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
Secondary	Incidence of desaturation	Presence of desaturation (pulse oximetry of lower than 94%) following dexmedetomidine infusion	From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
Secondary	Respiratory rate	Respiratory rate in units of /min, to examine whether respiratory depression or apnea occurs	From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
Secondary	Incidence of nausea	Incidence of nausea following dexmedetomidine infusion	From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion
Secondary	Incidence of vomiting	Incidence of vomiting following dexmedetomidine infusion	From start of dexmedetomidine infusion to 24 hours after end of dexmedetomidine infusion