Comparison Between Methadone and Morphine for Neonatal Opiate Withdrawal
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, Morphine (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Eastern Maine Medical Center Official(s) and/or principal investigator(s): Mark Brown, MD, Principal Investigator, Affiliation: Eastern Maine Medical Center
Summary
Hypothesis is that the effectiveness of opiate treatment with morphine will result in
shorter duration of opiate medication treatment and fewer infants treated with a second
drug.
Clinical Details
Official title: Evaluation of Efficacy of Methadone Versus Morphine for Treatment of Neonatal Abstinence Syndrome (NAS).
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment
Primary outcome: length of treatment with opioid medication
Secondary outcome: outcome frequency of second drug for withdrawal
Detailed description:
The purpose is to compare treatment of NAS with two different initial medications with
primary outcome of (1) reducing the duration of opiate medication treatment and (2) reducing
the number of infants treated with a second medication.
Design is a randomized, blinded comparison. The comparison is between methadone and morphine
Research Design:
a. Procedures: NAS scoring is currently done on infants meeting the inclusion criteria. NAS
scores are done every 2 hours for 24 hours and then every 4 hours when awake after feeding
for the duration of observation and treatment.
i. NAS scores may indicate more than withdrawal. Conditions such as colic (hypercaloric
formula, transient lactose intolerance), reflux, diaper irritation, prenatal SSRI exposure,
and nicotine withdrawal or baseline irritability may influence the variability of scores.
Decisions based on the NAS scores should take into account these factors for the infant.
b. Emergence of symptom, dosing, and initiation of treatment: Withdrawal significant enough
to warrant consideration for treatment is defined as 2 NAS scores >8. Once this threshold
has been reached and consent obtained, the infant is randomized to treatment arm, stratified
for prenatal exposure to methadone or buprenorphine. Twins will be randomized together to
the same arm. The treatment arms are either: i. Methadone (1 mg/mL) or morphine (1 mg/mL)
administered orally every 4 hours. The following is a dosing guide:
NAS Score Methadone or Morphine 8-12 0. 05 mg/kg/dose >13 0. 1 mg/kg/dose
1. Maximum dose of methadone or morphine will be 0. 2 mg/kg/dose. (NeoFax)
2. Additional doses, 0. 05 mg/kg, may be given every 12 hours as needed and added to the
next 24 hour's doses divided every 4 hours, until NAS scores are consistently <8 for 48
hours.
3. If the maximum dose of methadone or morphine is reached and if withdrawal is not
controlled, the infant will be started on clonazepam (0. 005 mg/kg/dose q 12h) per
current treatment.
c. Tapering medications: When the infant has NAS scores consistently <8 for 36 hours:
i. The taper will be on a daily basis of 10% of the final maintenance dose. Dosages
will be decreased in a measured amount to maintain NAS scores <8. After the last dose,
there will be a 24 to 36 hour observation period.
d. Non-tolerance of tapering: Non-tolerance of tapering is defined as 2 NAS scores >8
during the 12 hour period prior to the next taper dose: i. The tapering should be
stopped at the current level. ii. If necessary, an extra dose of methadone or morphine
can be given and added to the next day's dose divided into 6 doses. If withdrawal
re-emerges after this dose (2 NAS scores >8), then the maintenance dose should be
increased back to the last level; an extra dose may be given up to 4 to 5 hours after
the previous dose.
iii. If an extra dose is not given, the wean schedule can be resumed after 24 hours of
NAS scores <8; when dosing is resumed, the frequency should be changed to every 4 hours
with the same total daily dose.
e. Holding of doses: Methadone or morphine will be held for poor feeding, respiratory
depression, or somnolence at any time in the protocol.
Eligibility
Minimum age: N/A.
Maximum age: 28 Days.
Gender(s): Both.
Criteria:
Inclusion Criteria:
i. Evidence of opioid withdrawal clinically defined by at least 2 NAS scores > 8 in an 8
hour time period, AND
ii. Gestation => 35 weeks at entry defined by best obstetrical and physical exam criteria,
AND
iii. Medically stable condition in the opinion of the attending neonatologist, other than
opiate withdrawal, AND
iv. Mother on opiate replacement treatment therapy - methadone or buprenorphine.
Exclusion Criteria:
i. Gestation < 35 weeks at entry defined by best obstetrical and physical exam criteria.
ii. Hypoglycemia, hypomagnesaemia, or hypocalcemia until corrected,
iii. Serious medical illness such as sepsis, pneumonia, thyroid dysfunction, meningitis,
intracranial hemorrhage, perinatal depression, or respiratory failure requiring admission
to the NICU.
iv. Evidence of major congenital anomalies or genetic syndromes that impact the neonatal
course
v. Mother consistently taking prescribed benzodiazepine at the time of delivery
Locations and Contacts
Additional Information
Starting date: January 2011
Last updated: September 9, 2014
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