The Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome

Completed

• Conditions: Neonatal Abstinence Syndrome
• Interventions: Drug: Methadone

• Registration Number: NCT01754324
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

The chronic use of opiate medications during pregnancy is a major public health challenge. Prolonged exposure to opiates in utero may result in withdrawal symptoms in infants commonly referred to as neonatal abstinence syndrome (NAS). Signs of NAS may include irritability, high-pitched crying, muscle tightness, seizures, diarrhea, vomiting, poor feeding, and unstable body temperature. Many infants may be treated by supportive (non-pharmacological) therapy by minimizing stimulation, cuddling, responding promptly to hunger cues, and other comfort care. However, some infants continue to show severe symptoms of withdrawal despite these interventions. In these cases, infants may be treated with medications (pharmacological therapy). Although it has been several decades since the first descriptions of NAS, there still remains limited information with regards to the most effective treatment. We hypothesize that medical treatment protocols of NAS with methadone can be optimized by better understanding what the body does to the drug (the population-based pharmacokinetics of methadone).

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2012-12-14
• Study First Submitted QC: 2012-12-18
• Study First Posted: 2012-12-21
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2014-06
• Last Update Submitted: 2014-06-12
• Last Update Posted: 2014-06-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Chronic in utero exposure to opiates
2. Term infant, greater than or equal to 37 weeks gestation
3. Failure of non-pharmacologic treatment of NAS
4. Infant meets criteria for pharmacologic treatment of NAS as determined by physical findings consistent with drug withdrawal and Finnegan scoring system
5. The attending neonatologist chooses to treat the qualifying infant with oral methadone.

Exclusion Criteria

1. Prematurity
2. Congenital Abnormalities
3. Acutely ill neonates
4. Confounding medical illness necessitating therapy with opiates other than for NAS
5. Neonates whose only exposure to opiates were narcotics administered during labor
6. Infants who are wards of the state

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Methadone	Methadone	All infants requiring pharmacological treatment of their NAS symptoms are treated with a standardized protocol utilizing oral methadone. This treatment protocol has been the standard of care for infants with NAS at our institution for many years. Infants enrolled in this study will have blood samples drawn at predetermined times in order to obtain information regarding the pharmacokinetics of oral methadone in this population.

Primary Outcome Measures

Name	Time	Method
Methadone and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) blood concentration	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).	Timed blood samples will be collected to estimate pharmacokinetic parameters of oral methadone and its major metabolite EDDP using population pharmacokinetic methods.

Secondary Outcome Measures

Name	Time	Method
Failed Protocol Wean	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).	Blood specimens for the analysis of methadone and EDDP concentrations will be obtained from infants who do not tolerate the standard methadone dosing taper to investigate its utility in identifying rapid metabolizers of methadone.
Number of participants requiring adjunctive pharmacological treatment	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).	This endpoint will look at the number of patients who require supplemental phenobarbital in the treatment of NAS symptoms.
Length of hospitalization	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).	This endpoint will describe the number of days infants were hospitalized for treatment of NAS.
Readmission to the hospital	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks) and will complete a follow-up survey up to 2 weeks after hospital discharge.	This endpoint will describe the number of infants treated for NAS who later developed withdrawal symptoms after discharge that required readmission to the hospital.
Clinical resolution of NAS symptoms	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks) and will complete a follow-up survey up to 2 weeks after hospital discharge.	The length of medical therapy with oral methadone (in days) required to result in the clinical resolution of NAS symptoms will be measured.

Trial Locations

Locations (2)

The University Hospital; 🇺🇸 Cincinnati, Ohio, United States

Mercy Hospital Anderson; 🇺🇸 Cincinnati, Ohio, United States