Clonidine to Treat Iatrogenic-induced Opioid Dependence in Infants

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.

Conditions

• Neonatal Abstinence Syndrome

Interventions

DRUG

Clonidine HCL

At day 5 on opioid and/or benzodiazepine (BZD), the infant will be randomized to receive either placebo (normal saline) or clonidine 1μg/kg/q 4 hrs to a maximum dose of 2μg/kg/q 4. Weaning from the study drug: When the opioid is no longer required, 24 hrs later the study drug (placebo or study drug) will be reduced by 50% and then discontinued 24 hours later provided that the Modified Finnegan scores remain between \< 9.

DRUG

saline

Infants randomized to placebo will be administered IV saline or oral sterile water in the same volume as study drug. The placebo will be give every 4 hrs as outlined in the algorithm for the study.

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA)

  collaborator NIH

• Johns Hopkins University

  lead OTHER

Principal Investigators

• Estelle B Gauda, MD · Johns Hopkins University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

5 Days

Max Age

90 Days

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-07-31

Primary Completion

2011-07-31

Completion

2014-12-31

Countries

• United States

Study Locations