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

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.

Study Overview

• Status: Completed
• Conditions: Mechanical Ventilation Complication
• Intervention / Treatment: Drug: intermittent IV CLON

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intermittent IV CLON; Mechanically ventilated infants and children receive intravenous intermittentClonidine	Drug: intermittent IV CLON; Mechanically ventilated infants and children receive intravenous intermittent Clonidine instead of dexmedetomidine; Other Names: clonidine hydrochloride; Duraclon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Length of stay	Length of stay in PICU for sedative-analgesic therapy after stabilization and extubation.	2-8 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Sapna R Kudchadkar, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: August 11, 2014
• First Submitted That Met QC Criteria: September 23, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): March 1, 2021
• Last Update Submitted That Met QC Criteria: February 26, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: IRB00109563

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No