Intravenous Clonidine for Sedation in Infants and Children Who Are Mechanically Ventilated - Dosing Finding Study
Condition: Mechanical Ventilation Complication
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): intermittent IV CLON
Intervention type(s): Drug
Intervention description(s): Mechanically ventilated infants and children receive intravenous intermittent Clonidine instead of dexmedetomidine
Other intervention name(s): clonidine hydrochloride; Duraclon
Intervention MeSH terms: Clonidine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment