Drug Abuse, Drug Abuse in Pregnancy, Drug Addiction, Neonatal Abstinence Syndrome, Neonatal Opioid Withdrawal Syndrome, Opioid-Related Disorders, Pregnancy Related, Substance Abuse
Conditions
Keywords
CTN-0080, clinical trials network, medication assisted treatment
Brief summary
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
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.
Interventions
Weekly and monthly formulations of injectable, extended-release buprenorphine (BUP-XR).
Sublingual buprenorphine (BUP-SL), administered daily.
Sponsors
T. John Winhusen, PhD
National Institute on Drug Abuse (NIDA)
The Emmes Company, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
The primary outcome is assessed in a masked fashion by a central laboratory, but there is no masking for other outcomes.
Intervention model description
This is an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 41 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Illicit Opioid-negative Urine Samples During Pregnancy | From screening (at 6-30 weeks estimated gestational age) to delivery, an average of 10-34 weeks | Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of illicit opioids and/or their metabolites. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Illicit Opioid-negative Urine Samples Postpartum | Delivery through 12 months postpartum | Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of illicit opioids and/or their metabolites. |
| Percentage of Days With Study Medication Adherence During Pregnancy | From screening (at 6-30 weeks estimated gestational age) to delivery, an average of 10-34 weeks | Adherence to treatment from screening to delivery, checked weekly. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants. |
| Percentage of Days With Study Medication Adherence - Postpartum | Delivery through 12 months postpartum | Adherence to treatment from delivery through 12 months postpartum, checked weekly. |
| Percentage of Drug and Alcohol-negative Urine Samples During Pregnancy | From screening (at 6-30 weeks estimated gestational age) to delivery, an average of 10-34 weeks | Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of alcohol, illicit drugs and/or their metabolites. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants. |
| Percentage of Drug and Alcohol-negative Urine Samples - Postpartum Phase | Delivery through 12 months postpartum | Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of alcohol, illicit drugs and/or their metabolites, excluding cotinine. |
| Opioid Craving Scale - Pregnancy | Assessed at randomization (6-30 weeks estimated gestational age), two weeks post randomization and then monthly until delivery | 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. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants. The measure was assessed at randomization (6-30 weeks estimated gestational age), two weeks post randomization and then monthly until delivery, average score reported. |
| Opioid Craving Scale - Postpartum | Assessed at months 1, 3, 6, 9, and 12 post-delivery | The scale measures 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. The measure was assessed at months 1, 3, 6, 9, and 12 post-delivery, average score reported |
| Adequacy of Prenatal Care Utilization Index | At delivery | The information was derived from either medical records or the birth certificate. Information was not obtained for 74 participants. |
| Short Opiate Withdrawal Scale (SOWS)-Gossop - Pregnancy | Assessed at randomization (6-30 weeks estimated gestational age), two weeks post randomization and then monthly until delivery | Measure of maternal opioid withdrawal symptoms. The Short Opiate Withdrawal Scale-Gossop has scores rated on a scale of 0 (none) to 3 (severe) per question. The total score of the SOWS-Gossop ranges from 0-30. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants. The measure was assessed at randomization (6-30 weeks estimated gestational age), two weeks post randomization and then monthly until delivery, average score reported. |
| Short Opiate Withdrawal Scale (SOWS)-Gossop - Postpartum | Assessed at months 1, 3, 6, 9, and 12 post-delivery | Measure of maternal opioid withdrawal symptoms. The Short Opiate Withdrawal Scale-Gossop has scores rated on a scale of 0 (none) to 3 (severe) per question. The total score of the SOWS-Gossop ranges from 0-30. The measure was assessed at months 1, 3, 6, 9, and 12 post-delivery, average score reported. |
| Opioid Medication for Neonatal Opioid Withdrawal Syndrome (NOWS) Symptoms | Neonate discharge from hospital, typically within 1 month postpartum | Use of opioid medication for NOWS symptoms will be abstracted from the medical record. |
| Total Days of Neonatal Opioid Treatment During the Hospital Stay | Neonate discharge from hospital, typically within 1 month postpartum | Number of days of NOWS treatment for those infants that did receive it, abstracted from the medical record. |
| Infant Hospital Length of Stay | Neonate discharge from hospital, typically within 1 month postpartum | Infant hospital length of stay (LOS) defined as the infant's age, in days, at discharge will be abstracted from the medical record. (all infants) |
| Neonatal Opioid Withdrawal Syndrome (NOWS) Peak Score | Neonate discharge from hospital, typically within 1 month postpartum | NOWS peak score will be abstracted from the medical record. The scale used is the Finnegan-modified; the score ranges from 0-46, a score of 8 or higher indicates withdrawal. |
| Custody at Discharge | Neonate discharge from hospital, typically within 1 month postpartum | 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. Maternal custody - number \& percentage. |
| Child Protective Services Open Case | Neonate discharge from hospital, typically within 1 month postpartum | Whether or not there is an open child protective services at discharge (yes/no) will be abstracted from the medical record. Percentage of cases open with child protective services. |
| Ages and Stages Questionnaire, Third Edition (ASQ-3) | 12 months postpartum | To screen for developmental issues in the infant. Developmental issues at 12 months - percentage. Developmental issues assessed with The Ages and Stages Questionnaire, third edition scores each item as Yes (10 points), Sometimes (5 points), or Not Yet (0 points), with total scores compared to cutoffs to identify delays. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORT. John Winhusen, PhD
University of Cincinnati
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 31.2 years STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Opioid Craving Scale | 3.2 score on a scale STANDARD_DEVIATION 2.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 116 Participants |
| Sex: Female, Male Female | 71 Participants |
| Sex: Female, Male Male | 0 Participants |
| Short Opioid Withdrawal Scale | 6.4 score on a scale STANDARD_DEVIATION 6.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 71 | 0 / 67 | 1 / 70 |
| other Total, other adverse events | 49 / 69 | 59 / 71 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 9 / 69 | 27 / 71 | 9 / 67 | 11 / 70 |
Outcome results
None listed