Protocolized Initiation of Clonidine to Prevent Dexmedetomidine Withdrawal

NCT05575219 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HSC-MS-22-0410
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if the protocolized use of clonidine will reduce dexmedetomidine withdrawal symptoms, reduce PICU length of stay, and reduce costs related to sedation during hospital admission.

Conditions

Withdrawal; Therapeutic Substance

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Withdrawal

  The number of participants with withdrawal is reported. Withdrawal is defined as: (increase in heart rate, systolic blood pressure, and/or diastolic blood pressure by at least 10% from the 24 hours prior to dexmedetomidine weaning to the 24 hours after dexmedetomidine is discontinued) AND (two documented WAT (Withdrawal assessment tool)-1 scores of ≥ 3 and/or two study questionnaire scores of ≥ 3). WAT and questionnaire scores will be collected every 12 hours starting with the first dexmedetomidine wean until 72 hours after dexmedetomidine is discontinued. WAT-1 is a scoring tool used to evaluate symptoms of withdrawal with a total score that ranges from 0 to 12. The higher the score the more severe the withdrawal. The study questionnaire is used to evaluate degree of agitation and/or insomnia with a total score that ranges from 0 to 7, a higher score indicates higher degrees of agitation and/or insomnia.

  from the time dexmedetomidine is first weaned until 72 hours after dexmedetomidine is off (about 3-14 days)

Secondary Outcomes (4)

• Hours on Dexmedetomidine

  During time in Pediatric Intensive Care Unit (about 260 Hours)

• Pediatric Intensive Care Unit (PICU) Length of Stay

  During time in Pediatric Intensive Care Unit (about 10 to 30 days)

• Dexmedetomidine Cost Per Kilogram During Hospitalization

  During time in Pediatric Intensive Care Unit (about 24 days)

• Clonidine Cost Per Kilogram During Hospitalization

  During time in Pediatric Intensive Care Unit (about 24 days)

Study Arms (2)

Usual care (without protocolized clonidine initiation)

ACTIVE COMPARATOR

Participants will be observed for dexmedetomidine withdrawal and clonidine will be started at clinician discretion.

Drug: Clonidine (without protocolized initiation)

Intervention (protocolized clonidine initiation)

EXPERIMENTAL

A protocol for clonidine initiation will be implemented based on the time on dexmedetomidine and the average hourly dose of dexmedetomidine.

Drug: Clonidine (protocolized initiation)

Interventions

Clonidine (without protocolized initiation) DRUG

Participants will be observed for dexmedetomidine withdrawal and clonidine will be started at clinician discretion.

Also known as: Clondine

Usual care (without protocolized clonidine initiation)

Clonidine (protocolized initiation) DRUG

* Observe participants without initiating clonidine with dexmedetomidine infusion time of 72-119 hours. To wean off dexmedetomidine, decrease the infusion by 25% of the starting dose every 6 hours. * Begin clonidine at 1 mcg/kg enterally every 6 hours for participants with dexmedetomidine infusion time of 120-144 hours. * Begin clonidine at 1.5 mcg/kg enterally every 6 hours for participants with dexmedetomidine infusion times of 145-167 hours. * Begin clonidine at 2 mcg/kg enterally every 6 hours for participants with dexmedetomidine infusion time of \>/= 168 hours or with infusion time of 120-167 hours at doses \>/= 1.1 mcg/kg/min. * If clonidine is started decrease the dexmedetomidine infusion by 25% of the starting dose 1 hour after each dose of clonidine until off (wean every 6 hours).

Also known as: Clondine

Intervention (protocolized clonidine initiation)

Eligibility Criteria

• Age: 4 Weeks - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Dexmedetomidine infusion for greater than or equal to 72 hours

You may not qualify if:

• Admission for head trauma
• Psychiatric history
• Use of alpha-2 agonist medications at home
• Death while on dexmedetomidine

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

Children's Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

Related Publications (17)

• Berkenbosch JW. Dexmedetomidine and pediatric (cardiac) critical care--are we there yet? Pediatr Crit Care Med. 2010 Jan;11(1):148-9. doi: 10.1097/PCC.0b013e3181bc57c0. No abstract available.

  PMID: 20051795 BACKGROUND

• Berrens ZJ, Sauro AL, Tillman EM. Prevention of Withdrawal in Pediatric Patients Receiving Long-term Dexmedetomidine Infusions. J Pediatr Pharmacol Ther. 2021;26(1):81-86. doi: 10.5863/1551-6776-26.1.81. Epub 2021 Jan 4.

  PMID: 33424504 BACKGROUND

• Bhatt K, Thompson Quan A, Baumgartner L, Jia S, Croci R, Puntillo K, Ramsay J, Bouajram RH. Effects of a Clonidine Taper on Dexmedetomidine Use and Withdrawal in Adult Critically Ill Patients-A Pilot Study. Crit Care Explor. 2020 Nov 3;2(11):e0245. doi: 10.1097/CCE.0000000000000245. eCollection 2020 Nov.

  PMID: 33163969 BACKGROUND

• Curley MA, Harris SK, Fraser KA, Johnson RA, Arnold JH. State Behavioral Scale: a sedation assessment instrument for infants and young children supported on mechanical ventilation. Pediatr Crit Care Med. 2006 Mar;7(2):107-14. doi: 10.1097/01.PCC.0000200955.40962.38.

  PMID: 16446601 BACKGROUND

• Darnell C, Steiner J, Szmuk P, Sheeran P. Withdrawal from multiple sedative agent therapy in an infant: is dexmedetomidine the cause or the cure? Pediatr Crit Care Med. 2010 Jan;11(1):e1-3. doi: 10.1097/PCC.0b013e3181a66131.

  PMID: 20051785 BACKGROUND

• Franck LS, Harris SK, Soetenga DJ, Amling JK, Curley MA. The Withdrawal Assessment Tool-1 (WAT-1): an assessment instrument for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients. Pediatr Crit Care Med. 2008 Nov;9(6):573-80. doi: 10.1097/PCC.0b013e31818c8328.

  PMID: 18838937 BACKGROUND

• Franck LS, Scoppettuolo LA, Wypij D, Curley MAQ. Validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients. Pain. 2012 Jan;153(1):142-148. doi: 10.1016/j.pain.2011.10.003. Epub 2011 Nov 16.

  PMID: 22093817 BACKGROUND

• Haenecour AS, Seto W, Urbain CM, Stephens D, Laussen PC, Balit CR. Prolonged Dexmedetomidine Infusion and Drug Withdrawal In Critically Ill Children. J Pediatr Pharmacol Ther. 2017 Nov-Dec;22(6):453-460. doi: 10.5863/1551-6776-22.6.453.

  PMID: 29290746 BACKGROUND

• Lardieri AB, Fusco NM, Simone S, Walker LK, Morgan JA, Parbuoni KA. Effects of Clonidine on Withdrawal From Long-term Dexmedetomidine in the Pediatric Patient. J Pediatr Pharmacol Ther. 2015 Jan-Feb;20(1):45-53. doi: 10.5863/1551-6776-20.1.45.

  PMID: 25859170 BACKGROUND

• Liu J, Miller J, Ferguson M, Bagwell S, Bourque J. The Impact of a Clonidine Transition Protocol on Dexmedetomidine Withdrawal in Critically Ill Pediatric Patients. J Pediatr Pharmacol Ther. 2020;25(4):278-287. doi: 10.5863/1551-6776-25.4.278.

  PMID: 32461740 BACKGROUND

• Nguyen TL, Lam WM, Orr H, Gulbis B, Mauricio R, Tom E, Modem VM, Coronado-Munoz A. Clonidine for the Treatment of Agitation After Dexmedetomidine Discontinuation in Pediatric Patients: A Retrospective Cohort Study. J Pediatr Pharmacol Ther. 2021;26(8):821-827. doi: 10.5863/1551-6776-26.8.821. Epub 2021 Nov 10.

  PMID: 34790072 BACKGROUND

• Shutes BL, Gee SW, Sargel CL, Fink KA, Tobias JD. Dexmedetomidine as Single Continuous Sedative During Noninvasive Ventilation: Typical Usage, Hemodynamic Effects, and Withdrawal. Pediatr Crit Care Med. 2018 Apr;19(4):287-297. doi: 10.1097/PCC.0000000000001451.

  PMID: 29341985 BACKGROUND

• Thompson RZ, Gardner BM, Autry EB, Day SB, Krishna AS. Survey of the Current Use of Dexmedetomidine and Management of Withdrawal Symptoms in Critically Ill Children. J Pediatr Pharmacol Ther. 2019 Jan-Feb;24(1):16-21. doi: 10.5863/1551-6776-24.1.16.

  PMID: 30837809 BACKGROUND

• Traube C, Silver G, Kearney J, Patel A, Atkinson TM, Yoon MJ, Halpert S, Augenstein J, Sickles LE, Li C, Greenwald B. Cornell Assessment of Pediatric Delirium: a valid, rapid, observational tool for screening delirium in the PICU*. Crit Care Med. 2014 Mar;42(3):656-63. doi: 10.1097/CCM.0b013e3182a66b76.

  PMID: 24145848 BACKGROUND

• Weber MD, Thammasitboon S, Rosen DA. Acute discontinuation syndrome from dexmedetomidine after protracted use in a pediatric patient. Paediatr Anaesth. 2008 Jan;18(1):87-8. doi: 10.1111/j.1460-9592.2007.02377.x. No abstract available.

  PMID: 18095980 BACKGROUND

• Lee MM, Caylor K, Gockenbach N. Evaluating the Transition From Dexmedetomidine to Clonidine for the Prevention of Withdrawal in Critically Ill Pediatric Patients. J Pediatr Pharmacol Ther. 2020;25(2):104-110. doi: 10.5863/1551-6776-25.2.104.

  PMID: 32071584 BACKGROUND

• Miller JL, Allen C, Johnson PN. Neurologic withdrawal symptoms following abrupt discontinuation of a prolonged dexmedetomidine infusion in a child. J Pediatr Pharmacol Ther. 2010 Jan;15(1):38-42.

  PMID: 22477791 BACKGROUND

MeSH Terms

Interventions

Clonidine; clonidine 4-methylisothiocyanate

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Andrea Leigh Heifner, MD
• Organization: The University of Texas Health Science Center at Houston

andrea.heifner@stjude.org

407-729-2972

Study Officials

• Andrea Heifner, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Fellow

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 12, 2022
• Study Start: October 8, 2022
• Primary Completion: February 15, 2024
• Study Completion: February 15, 2024
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)