Intravenous Clonidine for Sedation in Infants and Children Who Are Mechanically Ventilated - Dosing Finding Study

Mechanical Ventilation Complication Clinical Trial

Official title:

Intravenous Clonidine for Sedation in Infants and Children Who Are Mechanically Ventilated - Dosing Finding Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02249039
• Other study ID #: IRB00109563
• Status: Completed
• Phase: Phase 1
• Start date: September 2015
• Est. completion date: December 2019

Study information

• Verified date: February 2021
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Critically ill infants and children who are mechanically ventilated are often given large doses of opiates and benzodiazepines to provide analgesia-sedation. These drugs significantly cause tolerance and dependence, depresses the drive to breathe, and thus prolongs the need for mechanical ventilation and the associated complications. We propose IV CLON could be used as effectively as DEX.

Description:

All critically ill mechanically ventilated infants and children receive intravenous analgesic-sedatives which often include opiates and benzodiazepines (BENZO). Undesirable side effects from these drugs include respiratory depression, tolerance and dependence. Alpha 2-adrenergic receptor agonists, dexmedetomidine (DEX) and clonidine (CLON) have excellent sedative-analgesics effects, do not cause respiratory depression and are opiate/BENZO sparing. While both are efficacious in providing sedation, several factors have led to a substantial increase in the use of the newer drug DEX over the more established drug CLON in adults, children and infants. However, studies to guide therapy and dosing for infants and children are lacking. While these infants and children do require less opiate/BENZO therapy and fewer days on mechanical ventilation, they quickly develop tolerance to and have significant withdrawal from DEX. This necessitates protracted weaning of DEX and longer length of stay in the pediatric intensive care unit (PICU) since DEX can only be administered as a continuous intravenous (IV) infusion. CLON, on the other hand, has a longer half-life and has formulations that allow for continuous or intermittent IV and oral administration. Dr. Gauda has an approved IND to use the epidural formulation of CLON intravenously in infants and children. The purpose of this pilot study is to determine the effective IV dosing scheme of CLON that can be safely used as an adjunct to analgesic-sedation management for infants and children in the PICU. It will include a total of 24 infants and children with 4 CLON and DEX exposed in each age stratum: 0-3, 4-6, and 7-12 months. We hypothesize that IV CLON can achieve optimal sedation and reduce the need for opiate/BENZO therapy in critically ill infants and children who would otherwise receive DEX, and thus, reduce the length of stay in the PICU. Data from this study will be used to inform a larger randomized trial and will directly benefit infants and children in Baltimore who are critically ill. Funds are requested to cover the cost of the CLON drug levels and the investigational pharmacy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Months

Eligibility

Inclusion Criteria:

• Infants and children age: 0-12 months
• Intubated and mechanically ventilated in the JHH PICU
• Meet criteria for starting dexmedetomidine (per PICU protocol)

Exclusion Criteria:

• Postoperative from complex congenital heart disease
• Asphyxia
• Traumatic Brain Injury
• Major Chromosomal anomaly (Trisomy 13, 18)
• Any infant or child who is receiving ECMO therapy
• If death is considered imminent

Related Conditions & MeSH terms

• Mechanical Ventilation Complication

Intervention

Drug:
• intermittent IV CLON
Mechanically ventilated infants and children receive intravenous intermittent Clonidine instead of dexmedetomidine

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sedation	Time spent (hrs) with a State Behavioral Scale <1 without the concurrent escalation of opiates or sedatives within 24 hrs after starting the CLON or DEX	2-8 weeks
Secondary	Frequency of cardiovascular occurrences	Frequency of cardiovascular occurrences i. =10 torr reduction in mean arterial blood pressure (MAP) ii. 20% drop in HR from the infant's baseline iii. Changes in HR or Blood pressure that triggers an intervention by the clinical team such as: -; Adding or escalating cardiotonic meds; holding the dose of timed sedative/analgesia	2 - 8 weeks
Secondary	Length of stay	Length of stay in PICU for sedative-analgesic therapy after stabilization and extubation.	2-8 weeks