Treatment of Neonatal Abstinence Syndrome

NCT01723722 | Completed Phase 4 Results DMC

• 1 other identifier: 07-2-M-107
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neonatal Abstinence Syndrome

Keywords

Neonatal Abstinence Syndrome; Methadone; Diluted Deodorized Tincture of Opium; dDTO; Phenobarbital

Outcome Measures

Primary Outcomes (1)

• Length of Treatment With Opioid Medication

  Up to 12 months

  Up to 12 months

Study Arms (2)

1 (Phenobarbital and Methadone)

ACTIVE COMPARATOR

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. 2. For the first 24 hours, doses will be prescribed every 6 hours 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 dose of methadone will be 0.15 mg/kg/dose. 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. For the following 24 hours, additional doses may be given every 6 hours as needed 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 pointthe 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.

Drug: Methadone

2 (Phenobarbital and Diluted Deodorized Tincture of Opium)

ACTIVE COMPARATOR

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. 2. The starting dose will be determined using a sliding scale in response to the last NAS score before starting. NAS Score Starting dDTO dose 8-11 0.4 mg/kg/day 12-15 0.6 mg/kg/day ≥16 0.8 mg/kg/day 3. The maximum dose of DTO will be 0.8 mg/kg/day. 4. After the first 24 hours of treatment, if the NAS scores are still ≥8, the dose will be increased to the next level. 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 methadone arm.

Drug: Diluted Deodorized Tincture of Opium

Interventions

Methadone DRUG

Concentration is 1mg/mL administered every 12 hours given on sliding scale in response to last NAS score.

Also known as: Dolophine

1 (Phenobarbital and Methadone)

Diluted Deodorized Tincture of Opium DRUG

Concentration is 1:24 dilution for a concentration of 0.4%

Also known as: Laudanum

2 (Phenobarbital and Diluted Deodorized Tincture of Opium)

Eligibility Criteria

• Age: 1 Day - 6 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eastern Maine Medical Center: lead

Study Sites (1)

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Related Publications (1)

• Zankl A, Martin J, Davey JG, Osborn DA. Opioid treatment for opioid withdrawal in newborn infants. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD002059. doi: 10.1002/14651858.CD002059.pub4.

  PMID: 34231914 DERIVED

MeSH Terms

Conditions

Neonatal Abstinence Syndrome

Interventions

Methadone

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Results Point of Contact

• Title: Dr Mark S Brown
• Organization: Eastern Maine Medical Center

mbrown@emh.org

207-973-8670

Study Officials

• Mark S. Brown, MD

  Eastern Maine Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Pediatric Service, Neonatalogy

Study Record Dates

• First Submitted: January 27, 2011
• First Posted: November 8, 2012
• Study Start: January 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: November 27, 2013
• Results First Posted: November 27, 2013

Record last verified: 2013-11

Locations

US (1)