Medication Treatment for Opioid Use Disorder in Expectant Mothers

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Medication Treatment for Opioid Use Disorder in Expectant Mothers (MOMs): a Pragmatic Randomized Trial Comparing Extended-release and Daily Buprenorphine Formulations

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

Intervention / Treatment
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* Drug: Buprenorphine Injection
* Drug: Buprenorphine Sublingual Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Potential participants must: be 18-41 years of age 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 have a single fetus pregnancy (can be based on self-report if an objective assessment is unavailable) 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 be willing to be randomized to BUP-XR or BUP-SL and to comply with study procedures, including weekly Medication Check Visits 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 be enrolled in outpatient addiction treatment at a participating site (e.g., have completed intake) be able to understand the study, and having understood, provide written informed consent in English Exclusion Criteria: Potential participants must not: have a physiological dependence on alcohol or sedatives requiring medical detoxification 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) 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 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; be currently receiving methadone or naltrexone for the treatment of OUD; 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; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 41 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BUP-XR<br>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.). | Drug: Buprenorphine Injection<br>* Weekly and monthly formulations of injectable, extended-release buprenorphine (BUP-XR).<br>* Other names: CAM2038;|
| Active Comparator: BUP-SL<br>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.). | Drug: Buprenorphine Sublingual Product<br>* Sublingual buprenorphine (BUP-SL), administered daily.<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of illicit opioid-negative urine samples during pregnancy | Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of illicit opioids and/or their metabolites. | Screening through delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total days of neonatal opioid treatment during the hospital stay | This outcome will be abstracted from the medical record. | Neonate discharge from hospital, typically within 1 month postpartum | 
| Proportion of illicit opioid-negative urine samples postpartum | Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of illicit opioids and/or their metabolites. | Delivery through 12 months postpartum | 
| Proportion of days with study medication adherence | Adherence to treatment during pregnancy through 12 months postpartum | Screening through 12 months postpartum | 
| Proportion of drug and alcohol-negative urine samples | Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of alcohol, illicit drugs and/or their metabolites. | Screening through 12 months postpartum | 
| Opioid Craving Scale | The scale consists of 3 items, measuring craving, cue-induced craving, and likelihood of using, rated on a visual analogue scale from 0-10. The total is calculated by averaging the 3 item scores. Higher scores indicate greater levels of opioid craving. | Screening through delivery | 
| Opioid Craving Scale | The scale consists of 3 items, measuring craving, cue-induced craving, and likelihood of using, rated on a visual analogue scale from 0-10. The total is calculated by averaging the 3 item scores. Higher scores indicate greater levels of opioid craving. | Delivery through 12 months postpartum | 
| Adequacy of Prenatal Care Utilization Index | The information will be derived from either medical records or the birth certificate. | At delivery | 
| Short Opiate Withdrawal Scale (SOWS)-Gossop | Measure of maternal opioid withdrawal symptoms. | Screening through 12 months postpartum | 
| Opioid Medication for Neonatal Opioid Withdrawal Syndrome (NOWS) Symptoms | Use of opioid medication for NOWS symptoms will be abstracted from the medical record. | Neonate discharge from hospital, typically within 1 month postpartum | 
| Infant Hospital Length of Stay | Infant hospital length of stay (LOS) defined as the infant's age, in days, at discharge will be abstracted from the medical record. (Infant) | Neonate discharge from hospital, typically within 1 month postpartum | 
| Adjunct Medications | Use of adjunct medications (e.g., phenobarbital, clonidine) will be abstracted from the medical record. | Neonate discharge from hospital, typically within 1 month postpartum | 
| Neonatal Opioid Withdrawal Syndrome (NOWS) Peak Score | NOWS peak score will be abstracted from the medical record. Because sites may use different NOWS scoring systems, the scoring system that was used will be included as part of the peak score abstraction. | Neonate discharge from hospital, typically within 1 month postpartum | 
| Diagnosis code for Neonatal Opioid Withdrawal Syndrome (NOWS) | A diagnosis code indicative of NOWS (Yes/No) will be abstracted from the medical record. | Neonate discharge from hospital, typically within 1 month postpartum | 
| Custody at discharge | For example, whether the infant is discharged in custody of mother, other relative, foster/adoptive family, etc. This will be abstracted from the medical record. | Neonate discharge from hospital, typically within 1 month postpartum | 
| Medications at discharge | Medications that the infant is to continue receiving at discharge will be abstracted from the medical record. | Neonate discharge from hospital, typically within 1 month postpartum | 
| Child protective services open case | Whether or not there is an open child protective services at discharge (yes/no) will be abstracted from the medical record. | Neonate discharge from hospital, typically within 1 month postpartum | 
| Ages and Stages Questionnaire, third edition (ASQ-3) | To screen for developmental issues in the infant. | 6 months postpartum | 
| Ages and Stages Questionnaire, third edition (ASQ-3) | To screen for developmental issues in the infant. | 12 months postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CTN-0080, clinical trials network, medication assisted treatment