Medication Treatment for Opioid Use Disorder in Expectant Mothers (MOMs)

T. John Winhusen, PhD

Status and phase: Completed; Phase 3

Conditions: Opioid-Related Disorders; Pregnancy Related; Drug Abuse; Neonatal Abstinence Syndrome; Substance Abuse; Drug Abuse in Pregnancy; Neonatal Opioid Withdrawal Syndrome; Drug Addiction

Treatments: Drug: Buprenorphine Injection; Drug: Buprenorphine Sublingual Product

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT03918850

UG1DA013732 (U.S. NIH Grant/Contract)

2019-0429-1

Details and patient eligibility

About

The primary objective of this study is to evaluate the impact of treating opioid use disorder (OUD) in pregnant women with extended-release buprenorphine (BUP-XR), compared to sublingual buprenorphine (BUP-SL), on mother and infant outcomes. The primary hypothesis is that the BUP-XR group will not have greater illicit opioid use than the BUP-SL group during pregnancy (non-inferiority).

Full description

This is an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial. Eligible participants will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, estimated gestational age (EGA) at time of randomization (6 weeks-18 weeks vs. 19 weeks-30 weeks), and whether they are on BUP-SL at the time of randomization (yes vs. no). Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum.

Enrollment: 140 patients

Sex: Female

Ages: 18 to 41 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Potential participants must:

1. be 18-41 years of age
2. be pregnant with an estimated gestational age (EGA) of 6 - 30 weeks at randomization, has evidence of a viable intrauterine pregnancy if EGA < 12 weeks and is not planning to terminate the pregnancy
3. have a single fetus pregnancy (can be based on self-report if an objective assessment is unavailable)
4. meet Diagnostic and Statistical Manual (DSM)-5 criteria for moderate/severe OUD and be a good candidate for BUP maintenance and/or be currently prescribed BUP for the treatment of OUD
5. be willing to be randomized to BUP-XR or BUP-SL and to comply with study procedures, including weekly Medication Check Visits
6. be planning to deliver at one of the hospitals for which the BORN survey was completed and that: a) has a written protocol for the management of neonatal abstinence syndrome (NAS) / neonatal withdrawal syndrome (NOWS), b) offers rooming-in while infants are being observed for NAS/NOWS; and c) does not send infants home on opioids for the treatment of NAS/NOWS
7. be enrolled in outpatient addiction treatment at a participating site (e.g., have completed intake)
8. be able to understand the study, and having understood, provide written informed consent in English

Exclusion criteria

Potential participants must not:

1. have a physiological dependence on alcohol or sedatives requiring medical detoxification

2. have a psychiatric condition that, in the judgment of the site medical clinician (MC), would make study participation unsafe or which would make treatment compliance difficult. Examples include:

   • Suicidal or homicidal ideation requiring immediate attention
   • Severe, inadequately-treated mental health disorder (e.g., active psychosis, uncontrolled bipolar disorder)

3. have a medical condition that, in the judgment of the study MC, would make study participation unsafe or which would make treatment compliance difficult. Medical conditions that may compromise participant safety or study conduct include, but are not limited to, allergy/sensitivity to study medications and the following based on clinical labs:

   • aspartate aminotransferase (AST) / alanine aminotransferase (ALT) greater than 5X upper limit of normal
   • serum creatinine greater than 1.5X upper limit of normal
   • total bilirubin greater than 1.5X upper limit of normal

4. be currently in jail, prison or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) that, in the judgement of the site investigator, could prevent participation in the study or in any study activities;

5. be currently receiving methadone or naltrexone for the treatment of OUD;

6. be enrolled in or planning to enroll in treatment beyond the level 3.3 (Clinically Managed Population-Specific High-Intensity Residential Services) of the American Society of Addiction Medicine criteria; for level 3.3, the participant must have the ability to leave the facility unaccompanied by staff as needed;

7. be enrolled in or planning to enroll in: a) a trial testing medication for managing OUD during pregnancy; b) research testing an intervention for substance use disorder or NOWS in their infant unless they are willing to provide a release for the research records.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

BUP-XR

Experimental group

Description:

Weekly subcutaneous Buprenorphine Injection (CAM2038) during pregnancy. During the 12-month postpartum phase, participants who are breastfeeding will continue receiving subcutaneous Buprenorphine Injection weekly; participants who are not breastfeeding will receive subcutaneous Buprenorphine Injection monthly. The target doses will be 24 mg for the weekly formulation and 96 mg for the monthly formulation, but the actual dose may be lower or higher as determined by the prescribing clinician (e.g., based on craving/withdrawal experienced by the participant, etc.).

Treatment:

Drug: Buprenorphine Injection

BUP-SL

Active Comparator group

Description:

Daily sublingual buprenorphine, with or without naloxone, based on site preference, during pregnancy and during the 12-month postpartum phase. The target dose will be 16 mg daily, but the actual dose may be lower or higher as determined by the prescribing clinician (e.g., based on craving/withdrawal experienced by the participant, etc.).

Treatment:

Drug: Buprenorphine Sublingual Product