Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome

Neonatal Abstinence Syndrome Clinical Trial

Official title:

Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02851303
• Other study ID #: 16-176
• Status: Completed
• Phase: Phase 4
• Start date: October 2016
• Est. completion date: September 30, 2018

Study information

• Verified date: May 2023
• Source: University of New Mexico
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: September 30, 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Hours to 12 Hours

Eligibility

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

Related Conditions & MeSH terms

• Neonatal Abstinence Syndrome
• Syndrome

Intervention

Drug:
• Morphine
Morphine wean protocol as described in arm description
• Methadone
Methadone wean protocol as described in arm description

Locations

Country	Name	City	State
United States	University of New Mexico Health Sciences Center	Albuquerque	New Mexico

Sponsors (1)

Lead Sponsor	Collaborator
University of New Mexico

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. Erratum In: Pediatrics. 2014 May;133(5):937. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: J Perinatol. 2015 Aug;35(8):667. Lehman, C U [corrected to Lehmann, C U]. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of Hospital Stay	Number of days in hospital after birth	assessed at hospital discharge, approximately 7-30 days
Secondary	Length of Treatment		assessed at hospital discharge, approximately 7-30 days
Secondary	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)	clonidine	assessed at hospital discharge, approximately 7-30 days
Secondary	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
Secondary	Need for NICU Transfer, as Determined by Chart Review of Discharge Summary.		assessed at hospital discharge, approximately 7-30 days
Secondary	Breastfeeding Initiation and Continuation at Hospital Discharge	Assessed through chart review of discharge summary documentation of method of infant feeding at time of discharge	assessed at hospital discharge, approximately 7-30 days
Secondary	Total Morphine Equivalent Dose Received		assessed at hospital discharge, approximately 7-30 days