Morphine vs Methadone for Neonatal Opioid Withdrawal Syndrome

Not currently recruiting at 28 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well two different methods help newborns with Neonatal Opioid Withdrawal Syndrome (NOWS) stop needing opioids like morphine or methadone. It compares a "rapid-wean" method, where the dose decreases quickly, to a "slow-wean" method, where the dose decreases more gradually. The goal is to determine which method helps babies stop needing the medicine faster. Eligible participants are babies born at least 36 weeks into pregnancy and currently taking morphine or methadone to manage symptoms from NOWS due to their mother's opioid use. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for newborns.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both methadone and morphine are safely used to treat infants with Neonatal Opioid Withdrawal Syndrome (NOWS). One study found no major difference in hospital stay duration or treatment needs when comparing methadone to morphine, indicating both medications are generally well-tolerated by newborns.

Further research supports methadone's safety, linking it to shorter hospital stays for infants, which suggests it is an effective and safe treatment. Additionally, mothers taking methadone can safely breastfeed, potentially easing withdrawal symptoms in their babies.

For morphine, similar safety information exists. It is commonly used in medical settings to manage NOWS, and no significant harmful effects on infants' development have been reported.

This trial further investigates both methadone and morphine, but existing research shows they are generally well-tolerated in newborns with withdrawal symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatments for Neonatal Opioid Withdrawal Syndrome (NOWS) because they are comparing the effects of Methadone and Morphine, two established medications, but with a twist. The trial is exploring two different dosing strategies: a "Rapid-wean" approach with 15% dose reductions and a "Slow-wean" approach with 10% reductions. These strategies could potentially lead to a more efficient and gentler weaning process for newborns, reducing the overall time and discomfort associated with withdrawal. If successful, this could optimize treatment protocols, providing a smoother transition for infants recovering from NOWS.

What evidence suggests that this trial's treatments could be effective for neonatal opioid withdrawal syndrome?

This trial will compare the effectiveness of methadone and morphine in treating neonatal opioid withdrawal syndrome (NOWS). Research has shown that methadone often leads to better treatment success for babies with NOWS compared to morphine. Some studies found that methadone is linked to shorter hospital stays for withdrawal. However, other studies comparing methadone and morphine found no significant difference in hospital stay duration or treatment length. Both methadone and morphine ease withdrawal symptoms in babies exposed to opioids before birth. These findings suggest that both treatments can be effective, but methadone might offer benefits in certain cases. ^{1 3 5 6 7}

Who Is on the Research Team?

Abbot R Laptook, MD

Principal Investigator

Women and Infants Hospital of Rhode Island

Adam Czynski, DO

Principal Investigator

Connecticut Children's Medical Center

Abhik Das, PhD

Principal Investigator

RTI International

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9202148/

Morphine versus methadone for neonatal opioid ... Discussion. This study showed no significant difference between length of stay or length of treatment between infants treated with methadone or ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31316147/

Comparative effectiveness of opioid replacement agents ... Conclusions: Methadone had superior primary treatment success compared with morphine. Buprenorphine was associated with the shortest overall durations of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02851303

Morphine Versus Methadone for Opiate Exposed Infants ... This study investigates the use of methadone versus morphine wean for the treatment of neonatal abstinence syndrome for infants exposed to opioids in utero.

4. jamanetwork.com jamanetwork.com/journals/jamapediatrics/fullarticle/2685283

Comparison of Safety and Efficacy of Methadone vs ... Methadone was associated with reductions in length of hospital stay, length of hospital stay attributable to neonatal abstinence syndrome, and ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2589933319301156

Delivery dose of methadone, but not buprenorphine, is ... Overall, the frequency of neonatal opioid withdrawal syndrome was not significantly different between the methadone and buprenorphine groups (56.8% vs 52.0%, P ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7919394/

Neonatal Opioid Withdrawal Syndrome (NOWS) One recent prospective cohort study showed promising data indicating that naltrexone-exposed infants (n = 121) had a lower rate of NOWS when compared to a ...

7. publications.aap.org publications.aap.org/pediatrics/article/146/5/e2020029074/75310/Neonatal-Opioid-Withdrawal-Syndrome

Neonatal Opioid Withdrawal Syndrome | Pediatrics In general, breastfeeding is safe for mothers who take methadone or buprenorphine and may reduce clinical signs of NOWS and length of hospital stay; thus ...