Morphine vs Methadone for Neonatal Opioid Withdrawal Syndrome

Recruiting at 27 trial locations

Overseen By Adam 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

Must not be taking: Buprenorphine, other opioids

Disqualifiers: Major birth defect, major surgery, seizures, others

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

189 Participants Needed

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. ^{1 2 3 4 5}

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. ^{2 6 7 8 9}

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. ^{2 3 4 10 11}

Research Team

Abbot R Laptook, MD

Principal Investigator

Women and Infants Hospital of Rhode Island

Abhik Das, PhD

Principal Investigator

RTI International

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.

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.

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 Overview The 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

Group I: Rapid-wean Active Control 2 Interventions

15% decrements from the stabilization dose of morphine/methadone

Group II: Slow-wean Active Control 2 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

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study. Sutter, MB., Watson, H., Yonke, N., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

A study of factors that influence the severity of neonatal narcotic withdrawal. [2013]

2. Ireland pubmed.ncbi.nlm.nih.gov

Therapy of the neonatal abstinence syndrome with tincture of opium or morphine drops. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Ineffective morphine treatment regimen for the control of Neonatal Abstinence Syndrome in buprenorphine- and methadone-exposed infants. [2014]

4. England pubmed.ncbi.nlm.nih.gov

Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Observation and treatment of neonatal narcotic withdrawal. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Buprenorphine for the treatment of perinatal opioid dependence: pharmacology and implications for antepartum, intrapartum, and postpartum care. [2013]

7. Australia pubmed.ncbi.nlm.nih.gov

Methadone levels and neonatal withdrawal. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Pharmacologic observations on the neonatal withdrawal syndrome. [2019]