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Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome

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ClinicalTrials.gov Identifier: NCT02851303
Recruitment Status : Recruiting
First Posted : August 1, 2016
Last Update Posted : July 26, 2017
Sponsor:
Information provided by (Responsible Party):
Mary Beth Sutter, University of New Mexico

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.

Condition or disease Intervention/treatment Phase
Neonatal Abstinence Syndrome Drug: Morphine Drug: Methadone Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : October 2016
Estimated Primary Completion Date : October 2017
Estimated Study Completion Date : January 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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
Drug: Morphine
Morphine wean protocol as described in arm description

Active Comparator: 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
Drug: Methadone
Methadone wean protocol as described in arm description




Primary Outcome Measures :
  1. Length of hospital stay [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]

Secondary Outcome Measures :
  1. Length of treatment [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]
  2. Patient satisfaction by HCAHPS Patient Satisfaction Survey Tool [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]
  3. 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) [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]
  4. Need for feeding assistance, determined by chart review of discharge summary, specifically evaluating for need for nasogastric tube placement or peripheral parenteral nutrition. [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]
  5. Need for NICU transfer, as determined by chart review of discharge summary. [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]
  6. Infant weight change [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]
  7. Breastfeeding initiation and continuation at hospital discharge [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]
    Assessed through chart review of discharge summary documentation of method of infant feeding at time of discharge

  8. Total morphine equivalent dose received [ Time Frame: assessed at hospital discharge, approximately 7-30 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02851303


Locations
United States, New Mexico
University of New Mexico Health Sciences Center Recruiting
Albuquerque, New Mexico, United States, 87106
Contact: Mary B Sutter, MD    443-386-6352    msutter@salud.unm.edu   
Contact: Nicole Yonke, MD       nyonke@salud.unm.edu   
Sponsors and Collaborators
University of New Mexico
Investigators
Principal Investigator: Mary Beth Sutter, MD Attending Physician, Assistant Professor

Publications:

Responsible Party: Mary Beth Sutter, Attending Physician, Assistant Professor, University of New Mexico
ClinicalTrials.gov Identifier: NCT02851303     History of Changes
Other Study ID Numbers: 16-176
First Posted: August 1, 2016    Key Record Dates
Last Update Posted: July 26, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Methadone
Syndrome
Neonatal Abstinence Syndrome
Disease
Pathologic Processes
Infant, Newborn, Diseases
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antitussive Agents
Respiratory System Agents