Randomized Control Trial of Buprenorphine vs. Morphine for the Treatment of Neonatal Opioid Withdrawal Syndrome (NOWS)

NCT ID: NCT04455802

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2021-05-17

Brief Summary

This randomized control trial will compare buprenorphine and morphine, two currently used medications for the treatment of neonatal opioid withdrawal syndrome (NOWS), in newborns to determine which medication will reduce the number of days of pharmacological treatment.

Detailed Description

This randomized control trial will compare buprenorphine to morphine, two currently used medications for the treatment of NOWS, to determine whether the use of buprenorphine for NOWS treatment will reduce the number of days of pharmacological treatment. After an infant is born they will be monitored for signs of NOWS. Once an infant reaches treatment thresholds, they will be randomized using a double dummy design to either the buprenorphine or morphine treatment arm. After randomization infants will receive a syringe with either morphine or placebo every 4 hours and every 8 hours infant will receive 1 sublingual application of buprenorphine or placebo. To maintain the blind infants enrolled in the study will receive both interventions. During the study medication doses will be weaned by 10% of the stabilization dose. Study intervention will continue until 20 percent of the maximal dose has been reached. Use of a second line drug will be permissible after randomization and after an infant has had 2 consecutive escalations. Second line drug will be phenobarbital, in addition to the study drug. Infants in both groups will be evaluated and scored for NOWS symptoms to determine if weaning study medication is permissible each day. NOWS scores that do not reach the threshold for escalation will wean in accordance with standard clinical practice. If NOWS symptoms increase during treatment, infants will have the dose of the study drug increased by 10% to the previous day's dose. When stable for 24 hours, the weaning process will continue. The NICU Network Neurobehavioral Scale (NNNS) will be administered prior to starting study medication and once off study medication but prior to discharge to examine proportion of infants in each medication arm for the abnormal NNNS profiles which has been associated with atypical early childhood outcomes including behavior problems and low IQ scores. Development at 18 months of age will also be assessed to examine any differences in both arms of the study.

Conditions

Neonatal Opioid Withdrawal Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Morphine

Infants randomized to the morphine arm will start at a dose of 0.06 mg/kg/dose every 4 hours. A buprenorphine placebo will also be given at the same frequency as a faux drug.

Group Type: ACTIVE_COMPARATOR

Buprenorphine or Placebo

Intervention Type: DRUG

The double blind, double dummy design necessitates that both drugs be on an identical schedule. The 4-hour dosing allows for this pairing. If a patient is randomized to the buprenorphine arm, medication administration will follow an every 8-hour dosing but medication will be substituted with placebo during the intermediary time point.

Morphine or Placebo

Intervention Type: DRUG

If a patient is randomized to the morphine arm, morphine will be given every 4 hours. Placebo will also be given at the same frequency as a faux drug.

Buprenorphine

Infants randomized to the buprenorphine arm will be started on a dose of 10 mg/kg/dose every 8 hours. A morphine placebo will also be given at the same frequency as a faux drug.

Patients can only be randomized to only one arm.

Group Type: EXPERIMENTAL

Buprenorphine or Placebo

Intervention Type: DRUG

The double blind, double dummy design necessitates that both drugs be on an identical schedule. The 4-hour dosing allows for this pairing. If a patient is randomized to the buprenorphine arm, medication administration will follow an every 8-hour dosing but medication will be substituted with placebo during the intermediary time point.

Morphine or Placebo

Intervention Type: DRUG

If a patient is randomized to the morphine arm, morphine will be given every 4 hours. Placebo will also be given at the same frequency as a faux drug.

Interventions

Buprenorphine or Placebo

The double blind, double dummy design necessitates that both drugs be on an identical schedule. The 4-hour dosing allows for this pairing. If a patient is randomized to the buprenorphine arm, medication administration will follow an every 8-hour dosing but medication will be substituted with placebo during the intermediary time point.

Intervention Type: DRUG

Morphine or Placebo

If a patient is randomized to the morphine arm, morphine will be given every 4 hours. Placebo will also be given at the same frequency as a faux drug.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Infant gestational age greater than or equal 36 weeks

2. Mother receiving either methadone from a drug treatment program, buprenorphine from a licensed physician, or an opioid prescription for a documented medical need

3. Mother had at least 2 prenatal appointments.

4. Infant toleration of oral medication administration

5. Infant is considered medically stable by the attending physician

6. Singleton Pregnancy

7. English Speaking

Exclusion Criteria

1. Within 30 days of birth the mother has actively used illicit drugs (excluding THC) or obtaining oral opioids, methadone, or buprenorphine from a non-licensed physician or drug treatment program

2. The mother has had less than 2 prenatal care visits

3. The mother reports excessive alcohol use during pregnancy

4. Mother is less than 18 years of age or is not capable of signing consent

5. The infant has a gestational age less than or equal to 35 weeks and 6 days

6. The infant has dysmorphic features including evidence of aneuploidy

7. The infant is not able to tolerate oral medication administration

8. Multiple gestation pregnancy

9. Hypoxic-ischemic encephalopathy

10. Seizures from etiologies other than NOWS

11. Non-English Speaking

12. Infant started on NOWS standard care medication prior to study consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: collaborator

Women and Infants Hospital of Rhode Island

OTHER

Sponsor Role: lead

Responsible Party

James Padbury

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adam J Czynski, DO

Role: PRINCIPAL_INVESTIGATOR

Women and Infants Hospital

Locations

Women and Infants Hospital

Providence, Rhode Island, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

1P20GM125507-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WIH 19-0042

Identifier Type: -

Identifier Source: org_study_id