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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Pregnancy Related; Opioid-Related Disorders; Substance Abuse; Drug Abuse; Drug Addiction; Neonatal Abstinence Syndrome; Drug Abuse in Pregnancy; Neonatal Opioid Withdrawal Syndrome
• Intervention / Treatment: Drug: Buprenorphine Injection; Drug: Buprenorphine Sublingual Product

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Frankie Kropp, MS; Phone Number: 513-585-8290; Email: kroppfb@ucmail.uc.edu
• Study Contact Backup: Name: Ben Kropp, MSLS; Phone Number: 513-585-8287; Email: kroppbn@ucmail.uc.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Gateway Community Services
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital HOPE Clinic
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Milagro Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati Health Perinatal Addictions Program
  • Oregon
    • Portland, Oregon, United States, 97214
      • CODA, Inc.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pregnancy Recovery Center at Magee-Womens Hospital of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah SUPeRAD Clinic
  • Washington
    • Seattle, Washington, United States, 98107
      • Addiction Recovery Services (ARS), Swedish Medical Center
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Marshall Health MARC Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 39 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BUP-XR; 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; Weekly and monthly formulations of injectable, extended-release buprenorphine (BUP-XR).; Other Names: CAM2038
Active Comparator: BUP-SL; 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; Sublingual buprenorphine (BUP-SL), administered daily.; Other Names: Subutex; Suboxone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: T. John Winhusen, PhD
• Collaborators: National Institute on Drug Abuse (NIDA); The Emmes Company, LLC
• Investigators: Principal Investigator: T. John Winhusen, PhD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2020
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: April 9, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: CTN-0080; clinical trials network; medication assisted treatment
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Disease; Infant, Newborn, Diseases; Narcotic-Related Disorders; Substance-Related Disorders; Syndrome; Opioid-Related Disorders; Substance Withdrawal Syndrome; Neonatal Abstinence Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: 2019-0429-1; UG1DA013732 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be transmitted by the study Data and Statistics Center to the designated party for de-identification, posting, storing, and archiving on NIDA's Data Share website. Data Share is an online repository of data from studies funded by the National Institute on Drug Abuse. All de-identified individual participant data is expected to be made available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No