Medication treatment for opioid use disorder in expectant mothers (MOMs): Design considerations for a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations

Abstract

Opioid use disorder (OUD) in pregnant women has increased significantly in recent years. Maintaining these women on sublingual (SL) buprenorphine (BUP) is an evidence-based practice but BUP-SL is associated with several disadvantages that an extended-release (XR) BUP formulation could eliminate. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial, Medication treatment for Opioid-dependent expectant Mothers (MOMs), to compare mother and infant outcomes of pregnant women with OUD treated with BUP-XR, relative to BUP-SL. A second aim is to determine the relative economic value of utilizing BUP-XR. Approximately 300 pregnant women with an estimated gestational age (EGA) of 6-30 weeks, recruited from 12 sites, will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, EGA, and BUP-SL status (taking/not taking) at the time of randomization. Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in two sub-studies to evaluate the: 1) mechanisms by which BUP-XR may improve mother and infant outcomes; and 2) effects of prenatal exposure to BUP-XR versus BUP-SL on infant neurodevelopment. This paper describes the key design decisions for the main trial made during protocol development. This Investigational New Drug (IND) trial uniquely uses pragmatic features where feasible in order to maximize external validity, hence increasing the potential to inform clinical practice guidelines and address multiple knowledge gaps for treatment of this patient population.

Subcutaneous Buprenorphine Extended-Release Use Among Pregnant and Postpartum Women

“…There is an ongoing clinical trial examining the safety, efficacy, and pharmacokinetics of an alternative N-methyl-2-pyrrolidone-free, extended-release buprenorphine in pregnant and postpartum women. 3 While awaiting the results from this trial, we strongly encourage clinicians to engage in shared decision making with their patients and are wary of a recommendation against this option based on the negative experiences of three patients.…”

Opioid Use in Pregnancy: A Review

“…Of note, extended-release buprenorphine is not standard of care in pregnancy, although there is a limited case series of 3 patients showing benefit 79 and an ongoing trial to assess its safety profile for use in pregnancy. 80 There are a variety of protocols for initiating buprenorphine for patients, including a standard induction protocol based on last substance use and low-dose inductions while on full opioid agonists. For patients desiring methadone, there is a slower titration due to its long half-life, although there is emerging evidence that a rapid titration can be done in settings of fentanyl or high opioid tolerance for faster maternal stabilization.…”

“…Ultimately, the treatment decision should be based on shared decision-making and patient preference. Of note, extended-release buprenorphine is not standard of care in pregnancy, although there is a limited case series of 3 patients showing benefit 79 and an ongoing trial to assess its safety profile for use in pregnancy 80 …”

Prenatal exposure to opioids.

“…Unfortunately, there is a lack of research comparing outcomes after medically versus nonmedically supervised withdrawal in which both groups receive the recommended longitudinal inpatient psychosocial treatment (WHO, 2014), and no randomized controlled trials have compared these treatment options (Terplan et al, 2018). The explosion in opioid use and its related negative effects has led to more research on different avenues of treatment for pregnant women with opioid addiction (e.g., extended release of buprenorphine; Winhusen et al, 2020) and collaboration of services across sectors (McConnell et al, 2020). However, there is still a critical need for more research regarding MAT versus nonpharmacological treatment of these women.…”