Treatment of Neonatal Abstinence Syndrome
Information source: Eastern Maine Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neonatal Abstinence Syndrome
Intervention: Methadone (Drug); Diluted Deodorized Tincture of Opium (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Eastern Maine Medical Center Official(s) and/or principal investigator(s): Mark S. Brown, MD, Principal Investigator, Affiliation: Eastern Maine Medical Center
Summary
This study compares treatment of Neonatal Abstinence Syndrome (NAS) with two different drugs
for the difference in the length of treatment. This is a randomized, open-label comparison
of phenobarbital and methadone versus phenobarbital and diluted deodorized tincture of opium
(dDTO) where phenobarbital is the initial drug used to stabilize neonatal withdrawal.
Clinical Details
Official title: Treatment of Neonatal Abstinence Syndrome: Evaluation of Efficacy of Phenobarbital in Combination With Either Methadone or Diluted Deodorized Tincture of Opium as Stabilizing and Tapering Regiments
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Length of Treatment With Opioid Medication
Detailed description:
a. Procedures: NAS scoring is currently done on infants meeting the inclusion criteria [IDD
29: 070]. NAS scores are initially done every 2 hours for 24 hours and then every 4 hours
when awake or before feeding for the duration of observation or treatment.
i. NAS scores may indicate more than withdrawal. Conditions such as colic, reflux, or
baseline irritability may influence the baseline scores. Decisions made based on the NAS
scores should take into account these factors and the baseline for the infant.
b. Emergence of symptom, dosing, and initiation of treatment: Withdrawal is defined as at
least 2 NAS scores >8 or 1 NAS score >12. Once withdrawal has emerged, the infant will be
given: i. Phenobarbital 20 to 30 mg/kg to load divided in up to 3 doses over 24 hours and
maintenance phenobarbital should be started at 2. 5 mg/kg/dose administered Q 12h, 12 hours
after the loading dose is ended. NAS scoring is continued and if scores remain <8 for a
minimum of 5 days after starting phenobarbital, the infant is eligible for discharge.
ii. If after phenobarbital treatment has been started, at least 2 NAS scores >8 or 1 NAS
score >12, then a phenobarbital level will be drawn and a mini-load calculated to reach a
level of 30 mg/dl. If withdrawal is not controlled or re-emerges after the mini-load dose,
the infant will be randomized to one of the two arms of the study - methadone or dDTO.
iii. Twins will be randomized together to the same arm. iv. Randomization will be stratified
into mothers on narcotic treatment >3 months and those not in treatment or <3 months.
Randomization will be done in blocks of 10 for each stratum.
v. For both drugs, the neonatal preparation will be used. vi. The following is a dosing
guide for methadone:
1. The neonatal concentration is 1 mg/ml of methadone. It is administered orally every 12
hours - standardized eventually to 0900 and 2100.
2. For the first 24 hours, doses will be prescribed every 6 hours for 4 doses, using a
sliding scale in response to the last NAS score:
NAS Score Methadone dose 8-11 0. 05 mg/kg/dose 12-15 0. 1 mg/kg/dose >16 0. 15 mg/kg/dose
3. Maximum loading dose of methadone will be 0. 15 mg/kg/dose Q 6 hour
4. After the first 24 hours of treatment, the total methadone dose will be summed and that
dose divided into two doses, given 12 hours apart. Subsequently, PRN doses of 0. 05
mg/kg/dose may be given every 6 hours for scores >8 X 2 and added to the next 24 hour's
doses, divided every 12 hours, until NAS scores are consistently <8 for 48 hours.
5. If at any point the maximum dose of methadone is reached and withdrawal is not
controlled, then in the opinion of two neonatologists the patient can be crossed-over
to the dDTO arm.
vii. The following is a dosing guide for dDTO:
1. The neonatal concentration is 1: 24 dilution for a concentration of 0. 4%, equivalent to
0. 4 mg/ml of morphine. It is administered orally every 4 hours - standardized
eventually to 0400, 0800, 1200, 1600, 2000, 0000.
2. The starting dose is determined by using a sliding scale in response to the last NAS
score before starting:
NAS Score dDTO dose 8-11 0. 1 mg/kg/day 12-15 0. 15 mg/kg/day >16 0. 2 mg/kg/day
For next day, the maintenance dose will return to the previous dose and given in 6
divided doses given Q 4 hours.
iv. For either methadone or dDTO, dosing will be held at this level and weaning will be
resumed when the infant has NAS scores <8 for 48 hours.
e. Holding of doses: Methadone or dDTO will be held for poor feeding, respiratory
depression, or somnolence at any time in the protocol.
f. Behavioral assessment: Behavioral assessment will be done by two methods. The
first by actigraphy and the second by NINS, both during the second week of weaning.
The latter will be done prior to a scheduled phenobarbital dose.
g. Formula: A 24 kcal/ounce formula should be fed initially using either standard
formula or by adding breast milk fortifier. During the weaning period, when weight
gain is >30 grams/day for at least 2 days, formula will be changed to 20 kcal/ounce and
weight gain monitored. If not sustained, then formula should be changed back to 24
kcal/ounce.
Eligibility
Minimum age: N/A.
Maximum age: 6 Days.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Evidence of opioid withdrawal clinically as defined by 2 NAS scores >8 or 1 NAS
score >12 over a 4 to 8 hour time period, AND
- Gestation >=35 weeks at entry defined by best obstetrical and physical exam criteria,
AND
- Medically stable condition, other than in opioid withdrawal, in the opinion of the
attending neonatologist, AND EITHER,
- Meconium or urine drug screen positive for opioids on mother or newborn, OR
- Known maternal prescription of opioids for chronic pain management during at least
the last trimester of pregnancy, OR
- Known maternal prescription of opioids for treatment of addiction, OR
- Suspected or admitted abuse with opioid drugs
- Infants of mothers with a medical or psychiatric diagnosis will not be excluded,
unless the maternal diagnosis precludes informed consent
Exclusion Criteria:
- Gestation <35 weeks at entry defined by best obstetrical and physical exam criteria.
- Hypoglycemia, hypomagnesaemia, or hypocalcaemia until corrected.
- Serious medical illness such as sepsis, pneumonia, hyperthyroidism, meningitis,
intracranial hemorrhage, perinatal depression, or respiratory failure requiring
admission to the NICU.
- Evidence of major congenital anomalies or genetic syndromes that impact the neonatal
course.
Locations and Contacts
Eastern Maine Medical Center, Bangor, Maine 04401, United States
Additional Information
Starting date: January 2007
Last updated: November 5, 2013
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