189 Participants Needed

Morphine vs Methadone for Neonatal Opioid Withdrawal Syndrome

Recruiting at 27 trial locations
AL
AD
AL
AC
Overseen ByAdam Czynski, MD
Age: Any Age
Sex: Any
Trial Phase: Phase 3
Sponsor: Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
Must be taking: Morphine, Methadone
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

The objective of this study is to evaluate the efficacy of a rapid wean intervention compared with a slow-wean intervention in reducing the number of days of opioid treatment from the first dose of weaning to cessation of opioid among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS).

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications. However, it focuses on infants already receiving morphine or methadone for neonatal opioid withdrawal syndrome, so these medications will continue as part of the study.

What data supports the effectiveness of morphine and methadone for treating Neonatal Opioid Withdrawal Syndrome (NOWS)?

Research shows that both morphine and methadone are used to treat NOWS, but there is no clear evidence that one is more effective than the other. A study found no significant differences in therapeutic response among infants treated with methadone, phenobarbital, and diazepam, suggesting methadone can be effective. However, another study indicated that morphine treatment did not significantly reduce withdrawal symptoms in methadone- and buprenorphine-exposed infants.12345

Is methadone or morphine safe for treating neonatal opioid withdrawal syndrome?

Methadone is commonly used to treat opioid dependence in pregnant women and is generally considered safe, but it can lead to neonatal abstinence syndrome (withdrawal symptoms in newborns). Morphine has been used to treat these withdrawal symptoms in newborns, and studies suggest it is safe for this purpose. Both medications have been studied in various settings and are generally safe when used under medical supervision.26789

How do methadone and morphine differ as drugs for treating neonatal opioid withdrawal syndrome?

Methadone and morphine are both used to treat neonatal opioid withdrawal syndrome, but methadone may offer a more stable treatment due to its longer half-life, which means it stays in the body longer and may require less frequent dosing compared to morphine. This can potentially lead to a shorter hospital stay and treatment duration for newborns.2341011

Research Team

Dr. Abbot Laptook, MD | Providence, RI ...

Abbot R Laptook, MD

Principal Investigator

Women and Infants Hospital of Rhode Island

AD

Abhik Das, PhD

Principal Investigator

RTI International

AC

Adam Czynski, DO

Principal Investigator

Connecticut Children's Medical Center

Eligibility Criteria

This trial is for newborns with Neonatal Opioid Withdrawal Syndrome (NOWS) who are at least 36 weeks gestational age, can take oral feeds and medications, and are receiving morphine or methadone. Hospitals must treat an average of 12 opioid-exposed infants yearly. Infants with seizures not due to NOWS, needing significant respiratory support, already weaning off opioids, having major surgery or defects, or planned discharge on opioids cannot participate.

Inclusion Criteria

Hospital Level: Hospital uses a scoring system to assess for signs of NOWS (original or modified Finnegan Neonatal Abstinence Scoring system, Eat-Sleep or Console)
My infant can take food and medicine by mouth.
My hospital treats at least 12 babies exposed to opioids yearly.
See 4 more

Exclusion Criteria

The baby has a significant birth defect, like gastroschisis.
My infant is being discharged on opioid medication.
Babies who have seizures caused by reasons other than Neonatal Opioid Withdrawal Syndrome (NOWS) will not be included.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stabilization

Infants are stabilized with an opioid to control NOWS signs before weaning begins

Variable, until stabilization is achieved
Daily evaluations

Weaning

Infants undergo either rapid or slow weaning of opioid treatment

Up to 35 days
Daily evaluations

Post-weaning Observation

Infants are observed in the hospital for at least 48 hours after cessation of opioid treatment

2 days
Continuous in-hospital observation

Follow-up

Participants are monitored for neurodevelopment and caregiver well-being at multiple intervals post-discharge

24 months
Visits at 1, 6, 12, 18, and 24 months

Treatment Details

Interventions

  • Methadone
  • Morphine
Trial OverviewThe study aims to compare two methods of reducing opioid treatment in infants with NOWS: a rapid wean versus a slow-wean approach. It measures the time from starting to reduce the dose until stopping it completely using either morphine or methadone as primary treatments.
Participant Groups
2Treatment groups
Active Control
Group I: Rapid-weanActive Control2 Interventions
15% decrements from the stabilization dose of morphine/methadone
Group II: Slow-weanActive Control2 Interventions
10% decrements from the stabilization dose of morphine/methadone

Methadone is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

🇺🇸
Approved in United States as Dolophine for:
  • Pain management
  • Opioid use disorder
🇪🇺
Approved in European Union as Methadose for:
  • Pain management
  • Opioid dependence
🇨🇦
Approved in Canada as Physeptone for:
  • Pain management
  • Opioid use disorder
🇯🇵
Approved in Japan as Heptadon for:
  • Pain management
🇨🇭
Approved in Switzerland as Heptanon for:
  • Pain management
  • Opioid dependence

Find a Clinic Near You

Who Is Running the Clinical Trial?

Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program

Lead Sponsor

Trials
3
Recruited
1,800+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials
2,103
Recruited
2,760,000+

Findings from Research

In a pilot study involving 61 infants with Neonatal Opioid Withdrawal Syndrome (NOWS), there were no significant differences in hospital length of stay (LOS) or length of treatment (LOT) between those treated with morphine and those treated with methadone.
However, infants treated with methadone received significantly higher total opioid doses and had a higher rate of transfer to the Neonatal Intensive Care Unit (NICU) due to over sedation, indicating potential safety concerns with methadone compared to morphine.
Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study.Sutter, MB., Watson, H., Yonke, N., et al.[2022]

References

A study of factors that influence the severity of neonatal narcotic withdrawal. [2013]
Therapy of the neonatal abstinence syndrome with tincture of opium or morphine drops. [2013]
Ineffective morphine treatment regimen for the control of Neonatal Abstinence Syndrome in buprenorphine- and methadone-exposed infants. [2014]
Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study. [2022]
Observation and treatment of neonatal narcotic withdrawal. [2019]
Buprenorphine for the treatment of perinatal opioid dependence: pharmacology and implications for antepartum, intrapartum, and postpartum care. [2013]
Methadone levels and neonatal withdrawal. [2019]
Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone. [2013]
Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal. [2013]
10.United Statespubmed.ncbi.nlm.nih.gov
Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial. [2018]
11.United Statespubmed.ncbi.nlm.nih.gov
Pharmacologic observations on the neonatal withdrawal syndrome. [2019]