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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.

SUBMITTER: Winhusen T

PROVIDER: S-EPMC7184985 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Winhusen Theresa T Lofwall Michelle M Jones Hendrée E HE Wilder Christine C Lindblad Robert R Schiff Davida M DM Wexelblatt Scott S Merhar Stephanie S Murphy Sean M SM Greenfield Shelly F SF Terplan Mishka M Wachman Elisha M EM Kropp Frankie F Theobald Jeff J Lewis Mitra M Matthews Abigail G AG Guille Connie C Silverstein Michael M Rosa Carmen C

Contemporary clinical trials 20200427

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 exp ...[more]

PMID: 32353544

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Project description:Importance:Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations. Objective:To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder. Design, Setting, and Participants:This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder. Interventions:Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group). Main Outcomes and Measures:Primary end points tested for noninferiority were response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority. Results:A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0% difference (95% CI, -4.0% to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7% difference (95% CI, -0.1% to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group. Conclusions and Relevance:Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages. Trial Registration:ClinicalTrials.gov Identifier: NCT02651584.

Project description:ImportanceExtended-release buprenorphine (XRB), a monthly injectable long-acting opioid use disorder (OUD) treatment, has not been studied for use in corrections facilities.ObjectiveTo compare treatment retention following release from jail among adults receiving daily sublingual buprenorphine-naloxone (SLB) vs those receiving XRB.Design, setting, and participantsThis open-label, randomized comparative effectiveness study included 52 incarcerated adults in New York City observed for 8 weeks postrelease between June 2019 and May 2020. Participants were soon-to-be-released volunteers from 1 men's and 1 women's jail facility who had OUDs already treated with SLB. Follow-up treatment was received at a primary care clinic in Manhattan. Data were analyzed between June 2020 and December 2020.InterventionsXRB treatment was offered prior to release and continued monthly through 8 weeks after release. SLB participants continued to receive daily directly observed in-jail SLB administration, were provided a 7-day SLB supply at jail release, and followed up at a designated clinic (or other preferred clinics).Main outcomes and measuresBuprenorphine treatment retention at 8 weeks postrelease.ResultsA total of 52 participants were randomized 1:1 to XRB (26 participants) and SLB (26 participants). Participants had a mean (SD) age of 42.6 (10.0) years; 45 participants (87%) were men; and 40 (77%) primarily used heroin prior to incarceration. Most participants (30 [58%]) reported prior buprenorphine use; 18 (35%) reported active community buprenorphine treatment prior to jail admission. Twenty-one of 26 assigned to XRB received 1 or more XRB injection prior to release; 3 initiated XRB postrelease; and 2 did not receive XRB. Patients in the XRB arm had fewer jail medical visits compared with daily SLB medication administration (mean [SD] visits per day: XRB, 0.11 [0.03] vs SLB, 1.06 [0.08]). Community buprenorphine treatment retention at week 8 postrelease was 18 participants in the XRB group (69.2%) vs 9 in the SLB group (34.6%), and rates of opioid-negative urine tests were 72 of 130 tests in the XRB group (55.3%) and 50 of 130 tests in the SLB group (38.4%). There were no differences in rates of serious adverse events, no overdoses, and no deaths.Conclusions and relevanceXRB was acceptable among patients currently receiving SLB, and patients had fewer in-jail clinic visits and increased community buprenorphine treatment retention when compared with standard daily SLB treatment. These results support wider use and further study of XRB as correctional and reentry OUD treatment.Trial registrationClinicalTrials.gov Identifier: NCT03604159.

Project description:ImportanceTo date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence.ObjectiveTo determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals.Design, setting and participantsA 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants.InterventionsRandomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks.Main outcomes and measuresPrimary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting.ResultsOf 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use.Conclusions and relevanceExtended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals.Trial registrationclinicaltrials.gov Identifier: NCT01717963.

Project description:Mothers have a significant influence on family dynamics, child development, and access to family services. There is a lack of literature on the typical Canadian maternal experience and its influence on access to services for mothers despite recognizing the importance of mothers. A cross-sectional study was conducted to address this research gap that employed Andersen's Behavioral Model of Health Service Use in conjunction with a feminist lens. A total of 1,082 mothers who resided in Newfoundland and Labrador (NL) participated in a province-wide survey in 2017 and reported on their wellbeing, family life, and healthcare utilization. Stepwise binomial logistic regressions and linear regressions were used to predict initiation and continued service utilization within the preceding 12 months, respectively. Mothers who participated in this survey were older, and were more likely to be in a relationship than those in the Canadian census, while no difference was observed in annual income. Approximately half of mothers accessed services for themselves over the previous 12-months, with the overwhelming majority accessing services for their children. Medical services were the most likely to be utilized, and mental health and behavioural services were the most likely services to be needed, but not available. Sociodemographic (e.g., age, education attainment), familial relationships and role satisfaction, health need, and health practices predicted maternal initiation and continued use of services, with a larger number of variables influencing maternal service initiation as compared to continuous use of services. Sociodemographic (e.g., maternal age, community population), maternal social support, health need, and maternal health practices predicted maternal access of at least one child service while family relationships, health need, and maternal health practices predicted maternal use of a range of child services conditional on initial access. These results can support the provincial health system to better support access to care by acknowledging the interdependent nature of maternal and child health care utilization. They also highlight the importance of equitable healthcare access in rural locations. Results are discussed in terms of their clinical relevance to health policy.

Project description:BackgroundCurrent guidelines for opioid dependence recommend daily maintenance of physical dependence with methadone or buprenorphine, and discourage abstinence due to the high risk of relapse and overdose. Extended-release formulations of the opioid antagonist naltrexone (XR-NTX) block heroin and other opioid agonists competitively for around 4 weeks per administration. XR-NTX thus enables opioid users to experience abstinence from opioid agonists with greatly reduced risk of overdose compared to medication-free abstinence. While XR-NTX has shown promise compared to placebo and daily naltrexone tablets, there is limited information on long-term safety and its performance compared to daily maintenance treatment.Methods/designIn this five-hospital RCT with long-term follow-up, we aim to recruit n = 180 patients in treatment for opioid dependence and allocate them in an open, randomized manner (1:1) to receive either 4-week XR-NTX or daily buprenorphine-naloxone (BP-NLX) for the duration of 12 weeks. Allocation is open-label due to the risk of overdose during attempts to self-unmask allocation using heroin. Urine drug tests are scheduled every week with follow-up visits & assessment every 4 weeks. Primary outcomes are abstinence from illicit opioids in urine drug tests and self-report, as well as retention in treatment. Secondary outcomes include other substance use, injecting behavior, drug craving, mental health, quality of life, treatment satisfaction, abstinence motivation, opioid agonist effect rating, insomnia, and pain. Observation is continued for another 36 weeks in order to assess longer-term safety, adherence and effectiveness. The study is an investigator-initiated trial, funded by public grants and approved by an Independent Ethical Committee (the Regional Ethical Committee for Research South-East B # 2011/1320) and the Norwegian Medicines Agency.DiscussionDespite minor implementation problems, the protocol appears sufficiently robust to generate results of high interest to patients, clinicians and policy makers.Trial registrationClinicaltrials.gov # NCT01717963 , first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012.

Project description:BackgroundUp to 50 % of women with gestational diabetes mellitus (GDM) will receive a diagnosis of type 2 diabetes mellitus (T2DM) within a decade after pregnancy. While excess postpartum weight retention exacerbates T2DM risk, lifestyle changes and behavior modifications can promote healthy postpartum weight loss and contribute to T2DM prevention efforts. However, some women have difficulty prioritizing self-care during this life stage. Efficacious interventions that women can balance with motherhood to reduce T2DM risk remain a goal. The objective of the Moms in Motion study is to evaluate the efficacy of a simple, novel, activity-boosting intervention using ankle weights worn with daily activities during a 6-month postpartum intervention among women with GDM. We hypothesize that women randomized to the 6-month intensity-modifying intervention will (1) demonstrate greater weight loss and (2) greater improvement in body composition and biomarker profile versus controls.MethodsThis study will be a parallel two-arm randomized controlled trial (n = 160). Women will be allocated 1:1 to an ankle weight intervention group or a standard-of-care control group. The intervention uses ankle weights (1.1 kg) worn on each ankle during routine daily activities (e.g., cleaning, childcare). Primary outcomes include pre- and post-assessments of weight from Visit 2 to Visit 3. Secondary outcomes include body composition, glycemia (2-h, 75 g oral glucose tolerance test), and fasting insulin. Exploratory outcomes include energy expenditure, diet, and psychosocial well-being.DiscussionBeyond the expected significance of this study in its direct health impacts from weight loss, it will contribute to exploring (1) the mechanism(s) by which the intervention is successful (mediating effects of energy expenditure and diet on weight loss) and (2) the effects of the intervention on body composition and biomarkers associated with insulin resistance and metabolic health. Additionally, we expect the findings to be meaningful regarding the intervention's effectiveness on engaging women with GDM in the postpartum period to reduce T2DM risk.Trial registrationThe ClinicalTrials.gov Identifier, is NCT03664089 . The trial registration date is September 10, 2018. The trial sponsor is Dr. Sarah A. Keim.

Dataset Information

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

Publications

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

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