Research Project
10441986
NIDA CTN Protocol 0080 Medication treatment for Opioid use disorder in expectant Mothers (MOMs): a pragmatic randomized trial comparing extended?release and daily buprenorphine formulations 1.1 Study Objectives CTN?0080 includes four objectives: ? Primary Objective: To evaluate the impact of treating opioid use disorder (OUD) in pregnant women with extended-release (XR) buprenorphine (BUP), compared to sublingual (SL) BUP, on mother and infant outcomes. Hypothesized outcomes are that the BUP-XR, relative to the BUP-SL, group will: 1) not have greater illicit opioid use during pregnancy (primary, non-inferiority); 2) have lower infant neonatal opioid withdrawal syndrome (NOWS) severity (key secondary, superiority); and 3) not have greater postpartum illicit opioid use (key secondary, non-inferiority). ? Secondary Objective: To test conceptual models of the mechanisms by which BUP-XR may improve mother-infant outcomes, relative to BUP-SL. ? Tertiary Objective: To determine the economic value of utilizing BUP-XR, relative to BUP- SL, to treat pregnant women. ? Quaternary Objective: To evaluate the impact of BUP-XR, relative to BUP-SL, on infant neurodevelopment. 1.2 Study Design 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. Participants will be invited to participate in the conceptual model assessment (CMA) sub?study, which will be used to evaluate the MOMs conceptual models. Infant caregivers will be invited to participate in the infant neurodevelopmental outcomes (INO) sub?study, which will include a 24?month child assessment. The INO data will be locked separately from the rest of the CTN?0080 database to allow CTN?0080 database lock following collection of the final (non?INO) CTN?0080 data point. 1.3 Study Population Approximately 200 pregnant women, recruited from approximately 10 sites, will be randomized into the trial. Sites that provide BUP to pregnant women in an office?based setting, offer BUP treatment following delivery for ?12 months, and admit enough potentially eligible women to meet the target randomization rate (1.25 per month) are eligible. The study population will include pregnant women who have an EGA of 6?30 weeks at randomization, and, in the judgment of the treating provider, are good candidates for BUP?maintenance treatment. All randomized participants will be encouraged to participate in the CMA and INO sub?studies. 1.4 Treatments Participants randomized to BUP?XR will receive a weekly formulation of CAM2038 during pregnancy. During the 12?month postpartum phase, women who are breastfeeding will continue receiving BUP?XR weekly while women who are not breastfeeding will receive monthly BUP?XR. Participants randomized to BUP?SL will receive buprenorphine, with or without naloxone, based on site preference, during pregnancy and the 12?month postpartum phase. 1.5 Assessments The primary outcome is illicit opioid abstinence during pregnancy, assessed by urine drug screens (UDSs). Key secondary outcomes for the primary objective are infant NOWS severity assessed by total days of opioid treatment (derived from medical records), and mother postpartum illicit opioid abstinence assessed by UDSs. The CMA sub?study includes assessments of: 1) maternal trough BUP plasma concentrations at study weeks 3 and 5; 2) fetal non?stress test and biophysical profile at ~36 weeks EGA at maternal peak BUP plasma level; 3) maternal peak and trough BUP plasma concentrations at ~36 weeks EGA; and 4) cord and maternal plasma BUP/BUP?metabolite levels at delivery. The main economic outcome will be the incremental cost?effectiveness ratio (ICER). The main neurodevelopmental outcome of the INO sub?study will be the cognitive subscale of the Bayley Scales of Infant and Toddler DevelopmentTM, Fourth Edition (BayleyTM?4) when the child is approximately 24 months of age. Study assessments will ideally occur at the clinic site; however, as needed these visits may occur in whole or in part via telemedicine, at other institutionally?affiliated clinical sites, or elsewhere in the community (including, but not limited to, home visits, visits at other non?affiliated clinical/laboratory sites, or other community sites affording appropriate safety and confidentiality) as permitted by the institution and other regulatory bodies. For the CMA and INO sub?studies, it is likely that some study procedures will occur outside the clinic at locations deemed most appropriate by the providers performing the study assessments (including, but not limited to, the delivery hospital, an external laboratory, or other clinical location). 1.6 Primary Analysis A Type?I error rate of ?=.025 will be used for the non?inferiority primary outcome analysis.
