Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome

NCT ID: NCT02851303

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2018-09-30

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.

Detailed Description

Neonates exposed to opiates in utero can develop a constellation of withdrawal symptoms known as neonatal abstinence syndrome (NAS). Infants with NAS are at risk for multiple medical complications including failure to thrive and seizures, they often require prolonged hospital stays and account for significant health care costs. At University of New Mexico, infants exposed to methadone or heroin in utero who develop NAS requiring pharmacologic treatment undergo a treatment wean with methadone, whereas infants exposed to buprenorphine undergo a wean with morphine. However, morphine is used frequently to treat neonatal abstinence syndrome among methadone-exposed infants throughout the US, and optimal pharmacologic treatment for NAS remains unknown. Anecdotal evidence at the investigators institution suggests that infants treated with morphine have shorter hospital stays compared to infants treated with methadone. Investigators propose a pilot randomized controlled trial to evaluate morphine vs methadone treatment of infants with in-utero methadone or heroin exposure. Specifically, length of treatment, need for additional medication to treat withdrawal, and length of hospital stay will be compared.

When women are admitted to Labor and Delivery and/or up to 12 hours postpartum, research staff will approach patients about study enrollment. Participants will be approached for study enrollment if medication list on admission includes methadone, if participants self-report methadone use prenatally, and/ or if urine drug screen is positive for methadone or opiates on admission. If women choose to enroll in the study, and their infants require treatment for NAS, their infants will be randomized and assigned a study number for treatment using the methadone or morphine protocols at the time treatment is required.

All infants will be monitored for signs of withdrawal using the standard UNM NAS scoring protocol. Standard of care at UNM is to treat infants exposed to opioids in-utero with methadone if they require pharmacologic therapy for NAS, therefore treatment will not be withheld if they choose not to enroll in the study. Standard of care is also to obtain a urine drug screen on all infants with reported exposure to opiates in pregnancy. Enrolled patients will thus undergo routine urine drug screening. The only difference from standard care with regards to the study protocol is the treatment of half of the methadone or heroin exposed infants with morphine. The morphine protocol is proven for safety and efficacy currently in buprenorphine exposed infants. Once randomized, infants will continue on the protocol until discharge. At discharge, parents will complete a patient satisfaction survey.

Conditions

Neonatal Abstinence Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Morphine

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

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

Morphine wean protocol as described in arm description

Methadone

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

Group Type: ACTIVE_COMPARATOR

Methadone

Intervention Type: DRUG

Methadone wean protocol as described in arm description

Interventions

Morphine

Morphine wean protocol as described in arm description

Intervention Type: DRUG

Methadone

Methadone wean protocol as described in arm description

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

• Minimum Eligible Age: 0 Hours
• Maximum Eligible Age: 12 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of New Mexico

OTHER

Sponsor Role: lead

Responsible Party

Mary Beth Sutter

Attending Physician, Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary Beth Sutter, MD

Role: PRINCIPAL_INVESTIGATOR

Attending Physician, Assistant Professor

Locations

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 22291123 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25927272 (View on PubMed)

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.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 7000060 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23314720 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 21142534 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35705944 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34231914 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

16-176

Identifier Type: -

Identifier Source: org_study_id