Clonidine to Treat Iatrogenic-induced Opioid Dependence in Infants
|Neonatal Abstinence Syndrome||Drug: Clonidine HCL Drug: saline||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Efficacy of Clonidine in Reducing Iatrogenic-induced Opioid Dependence in Infants:|
- Time to Complete Detoxification [ Time Frame: up to 4 weeks ]Time to complete detoxification is defined as 48 hrs off all opioids/benzodiazepines and study drug with acceptable withdrawal scores of <9 (on average we expect the infant to be enrolled in the study for 2-4 weeks). The scale used to assess withdrawal was the Modified Finnegan Neonatal Withdrawal Scale, which ranges from 0-41, 0 represents no withdrawal and 41 represent maximum withdrawal.
- Cardiovascular Side-effects Changes HR and BP [ Time Frame: 48 hrs after starting study drug and for 48hrs after stopping study drug ]Changes in Heart Rate (HR) and BP for 48 hrs after starting study drug and for 48hrs after stopping study drug
- Cumulative Dose of Opioid and Benzodiazepine [ Time Frame: 2-4 weeks ]We will determine the total amount of opioid and benzodiazepine needed from the start of detoxification to the end of the the detoxification.
|Study Start Date:||July 2011|
|Study Completion Date:||December 2014|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
Interventions: Infants will receive intravenous or oral clonidine(Duraclon) for the treatment of pain and sedation: Duration: (Clonidine HCL) 1 mcg/kg/dose q4 either iv or po.
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.
Other Name: Duraclon
Placebo Comparator: Control
Intervention: Infants will receive place (saline) (if receiving it IV) or orally (sterile water) if receiving it orally
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.
Other Name: placebo, sterile water, saline
The study will test the following 2 specific aims:
Specific Aim 1
To determine the efficacy and short-term safety of clonidine in reducing the severity of iatrogenic neonatal abstinence syndrome (NAS) by decreasing the time required for complete sedative and analgesic drug detoxification. The investigators will enroll 88 neonates at risk for having moderate to severe NAS in a randomized, double-blinded placebo controlled trial comparing opioid/benzodiazepine administration combined with a placebo (control) vs. opioid/benzodiazepine combined with clonidine. Principal outcome measure will be the difference in length of treatment for complete detoxification. Early safety of clonidine will be determined by monitoring for cardiorespiratory side effects that might be associated with clonidine use in this high risk population.
Specific Aim 2
To determine the pharmacokinetics and pharmacodynamics of clonidine in this critically ill infant population. The investigators will estimate the dose-exposure-response relationship of clonidine in neonates at risk for developing iatrogenic by using nonlinear mixed-effects population pharmacokinetic (PK)-pharmacodynamic (PD) analysis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01360450
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Estelle B Gauda, MD||Johns Hopkins University|