Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome

NCT02851303 | Completed Phase 4 Results DMC

• 1 other identifier: 16-176
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the use of methadone versus morphine wean for the treatment of neonatal abstinence syndrome for infants exposed to opioids in utero. Half of infants who require pharmacotherapy for NAS will receive a methadone wean, and half will receive a morphine wean. Length of hospital stay, length of treatment and parent satisfaction will be studied.

Conditions

Neonatal Abstinence Syndrome

Outcome Measures

Primary Outcomes (1)

• Length of Hospital Stay

  Number of days in hospital after birth

  assessed at hospital discharge, approximately 7-30 days

Secondary Outcomes (6)

• Length of Treatment

  assessed at hospital discharge, approximately 7-30 days

• Need for Additional Agent to Treat Withdrawal, Determined by Chart Review of Medication Administration Record of Administered Medications for Withdrawal Treatment (Example: Clonidine or Phenobarbital)

  assessed at hospital discharge, approximately 7-30 days

• Need for Feeding Assistance, Determined by Chart Review of Discharge Summary, Specifically Evaluating for Need for Nasogastric Tube Placement or Peripheral Parenteral Nutrition.

  assessed at hospital discharge, approximately 7-30 days

• Need for NICU Transfer, as Determined by Chart Review of Discharge Summary.

  assessed at hospital discharge, approximately 7-30 days

• Breastfeeding Initiation and Continuation at Hospital Discharge

  assessed at hospital discharge, approximately 7-30 days

Study Arms (2)

Morphine

ACTIVE COMPARATOR

Dose given q 3 - 4 hrs with feeds; do not exceed 4 hrs between doses Morphine (0.04mg/0.1ml) Score Dose For Initiation 0-8 0 None 9-12 0.04 mg/dose 13-16 0.08 mg/dose 17-20 0.12 mg/dose 21-24 0.16 mg/dose 25 or above 0.20mg/dose Morphine Maintenance/Escalation * Maintain dose if score 0-8 * Increase dose by 0.02 if score is 9-12 (rescore before dosing) • Increase dose by 0.04 if score 13-16 * Increase score by 0.06 if score 17-20 Weaning Instructions: * Maintain on dose 48 hrs before starting weaning * Wean 0.02 mg morphine every day for a score is 0-8 • Defer wean for score 9-12 Re-escalation * If neonate scores 9-12 re-score as described for initiation, * If second score is in 9-12 increase morphine 0.01 mg q3-4 hrs • If 2 consecutive scores 13-16, increase 0.02 mg q3-4 hrs * If 2 consecutive scores in 17-20, increase 0.04 mg q3-4 hrs etc

Drug: Morphine

Methadone

ACTIVE COMPARATOR

Step 1: 0.7 mgs/Kg/24 hrs. divided by into six doses (q 4 hrs) is starting dose Step 2: Decrease dose by half, which is 50% of starting dose, EVERY 4 hours. Step 3: Same dose which is 50% of starting dose EVERY 6 hours. Step 4: Same dose which is 50% of starting dose EVERY 8 hours. Step 5: Same dose which is 50% of starting dose EVERY 12 hours. Step 6: Decrease dose by half, which is 25% of starting dose EVERY 12 hours. Step 7: Same dose which is 25% of starting dose q 24 hours

Drug: Methadone

Interventions

Morphine DRUG

Morphine wean protocol as described in arm description

Morphine

Methadone DRUG

Methadone wean protocol as described in arm description

Methadone

Eligibility Criteria

• Age: 0 Hours - 12 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Born at University of New Mexico Hospital
• Greater than 34 weeks gestation
• Primary in-utero drug exposure was opioids other than buprenorphine
• Maternal or infant urine drug screen positive for methadone and/or opioids on admission

You may not qualify if:

• Born prior to 34 weeks
• Neonatal intensive care unit admission
• Serious medical comorbidities
• Primary substance exposure in-utero was buprenorphine, or was not opioids

Sponsors & Collaborators

• University of New Mexico: lead

Study Sites (1)

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87106, United States

Location

Related Publications (9)

• Hudak ML, Tan RC; COMMITTEE ON DRUGS; COMMITTEE ON FETUS AND NEWBORN; American Academy of Pediatrics. Neonatal drug withdrawal. Pediatrics. 2012 Feb;129(2):e540-60. doi: 10.1542/peds.2011-3212. Epub 2012 Jan 30.

  PMID: 22291123 BACKGROUND

• Patrick SW, Davis MM, Lehmann CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012. J Perinatol. 2015 Aug;35(8):650-5. doi: 10.1038/jp.2015.36. Epub 2015 Apr 30.

  PMID: 25927272 BACKGROUND

• Hall ES, Wexelblatt SL, Crowley M, Grow JL, Jasin LR, Klebanoff MA, McClead RE, Meinzen-Derr J, Mohan VK, Stein H, Walsh MC; OCHNAS Consortium. A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome. Pediatrics. 2014 Aug;134(2):e527-34. doi: 10.1542/peds.2013-4036.

  PMID: 25070317 BACKGROUND

• Winter M, Nelson DS, Milton GW. Leucocyte adherence inhibition test for the detection of cell-mediated immunity to malignant melanoma. Aust N Z J Med. 1980 Aug;10(4):405-9. doi: 10.1111/j.1445-5994.1980.tb04090.x.

  PMID: 7000060 BACKGROUND

• Logan BA, Brown MS, Hayes MJ. Neonatal abstinence syndrome: treatment and pediatric outcomes. Clin Obstet Gynecol. 2013 Mar;56(1):186-92. doi: 10.1097/GRF.0b013e31827feea4.

  PMID: 23314720 BACKGROUND

• Hall ES, Wexelblatt SL, Crowley M, Grow JL, Jasin LR, Klebanoff MA, McClead RE, Meinzen-Derr J, Mohan VK, Stein H, Walsh MC; OCHNAS Consortium. Implementation of a Neonatal Abstinence Syndrome Weaning Protocol: A Multicenter Cohort Study. Pediatrics. 2015 Oct;136(4):e803-10. doi: 10.1542/peds.2015-1141. Epub 2015 Sep 14.

  PMID: 26371196 BACKGROUND

• Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Selby P, Martin PR, Fischer G. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010 Dec 9;363(24):2320-31. doi: 10.1056/NEJMoa1005359.

  PMID: 21142534 BACKGROUND

• Sutter MB, Watson H, Yonke N, Weitzen S, Leeman L. Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study. BMC Pediatr. 2022 Jun 15;22(1):345. doi: 10.1186/s12887-022-03401-3.

  PMID: 35705944 DERIVED

• 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

Morphine; 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)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Ketones; Organic Chemicals

Results Point of Contact

• Title: Dr. Mary Beth Sutter
• Organization: Brown Family Medicine

marybeth_sutter@brown.edu

401-921-7981

Study Officials

• Mary Beth Sutter, MD

  Attending Physician, Assistant Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Attending Physician, Assistant Professor

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: August 1, 2016
• Study Start: October 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: September 30, 2018
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)