Clonidine to Treat Iatrogenic-induced Opioid Dependence in Infants
Status:
Terminated
Trial end date:
2014-12-01
Target enrollment:
Participant gender:
Summary
Thousands of critically ill infants (and children) are exposed to opioids and benzodiazepines
to achieve sedation and analgesia as part of routine care in neonatal and pediatric intensive
care units. While the use of these agents are undisputedly beneficial in reducing pain and
anxiety, improving ventilation, reducing pulmonary vascular resistance and improving
outcomes; the consequence is often the development of tolerance and physiologic dependence -
similar to prenatal exposure from these same classes of drugs. The investigators have
recently reported the results of randomized placebo control trial showing that the addition
of clonidine (central alpha 2 agonist) to tapering doses of opioids was efficacious and safe
in treating opioid dependence in infants who had moderate to severe neonatal abstinence
syndrome from prenatal drug exposure to opioids. Currently, the investigators propose to
perform a double-blind, randomized placebo control trial in a cohort of critically ill
infants without prenatal drug exposure at Johns Hopkins Hospital to test the overall
hypothesis that early addition of clonidine to a cohort of critically ill neonates on
mechanical ventilation who are receiving opioids and benzodiazepines for analgesia and
sedation will be efficacious and safe in reducing both the incidence and severity of
withdrawal symptoms (NICU-NAS); as well as, reducing the time to complete sedative and
analgesic drug detoxification. The hypothesis will be tested by addressing 2 specific aims
that will determine: 1) the efficacy and safety of clonidine in critically ill infants, and
2) pharmacokinetics and pharmacodynamics using population-based pharmacokinetics in this
vulnerable infant population who have only been exposed to these drugs as part of their
routine care. Many "standard of care practices" are incorporated in neonatal and pediatric
care prior to evidence based studies. This proposal will fill a much needed gap in
translating what the investigators have learned about basic mechanisms mediating dependence
and withdrawal to proven therapies for vulnerable pediatric populations.