Study 41 – Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy

CTN-0100: Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy

Investigators:  Edward Nunes, M.D., John Rotrosen, M.D., & Roger Weiss, M.D.

Release Date:  TBA

Objective: Although medications for opioid use disorder (MOUD) are highly effective, most studies show > 50% dropout at 3–6 months, and dropout carries a high risk of relapse. Among those who adhere to MOUD and do well, many want to discontinue at some point, but little is known about how to advise and manage such patients to minimize risk of relapse. This project aims to test pharmacological and behavioral strategies to 1) improve MOUD retention, and 2) improve outcome among patients who have been successfully stabilized on MOUD and want to stop medication. The project will also determine patient characteristics associated with relapse after discontinuation, and develop a predictive relapse risk model.

Significance/Impact: Although patients who take MOUD have significantly better outcomes than those who do not do so, retaining people in MOUD remains a major challenge. Further, no studies have addressed the question of who can safely discontinue MOUD, and how they can best do so. The strategies that will be evaluated in this trial are designed to be practical and feasible, such that if found effective, they have potential for widespread and sustainable dissemination, and thus potential to reduce the public health impact of OUD by improving the delivery of MOUD. This study would also be the first to prospectively follow a large sample of patients through discontinuation to better understand prognostic factors for relapse versus stable recovery off of medication.

Study Design/Methodology: This pragmatic effectiveness trial will enroll patients at approximately 21 sites including both primary care and addiction specialty care settings. In the MOUD Retention sub-study, treatment-seeking patients (n=2000) will first choose between BUP or XR-NTX. Those choosing BUP (n≈1500) will be randomized in a 3 x 2 factorial design to one of 3 medication conditions: 1) Standard SL-BUP dose (16 mg target); 2) High SL-BUP dose (32 mg target); 3) XR-BUP, and two behavioral intervention conditions: 1) Treatment as Usual (TAU); or 2) TAU plus Assertive Case Management with Incentives contingent on adherence (ACM+I). Those choosing XR-NTX (n≈500) will be randomized to the 2 behavioral conditions. The study will provide treatment for 24 months; the primary “retention outcome” will be retention in MOUD at 6 months, with 12 and 24-month retention among other secondary outcomes.

In the MOUD Discontinuation sub-study, patients (n≈500) who are stable and have completed at least 2 years on SL-BUP treatment and want to stop will be randomized to 1) Gradual taper of SL-BUP vs. 2) Transition to XR-NTX, then discontinuation of XR-NTX if the patient chooses to do so. In a 2 x 2 design, the study will also test a behavioral strategy, a technology-based relapse prevention tool (CBT4CBT), to coach patients on strategies to avoid relapse. Stable XR-NTX patients (n≈500) who wish to discontinue after 2 years of treatment will be randomized to CBT4BCT + TAU vs. TAU and will stop receiving XR-NTX. The primary “discontinuation outcome” will be successful discontinuation and no relapse over 1 year.

All patients entering the retention sub-study, including those who subsequently enter the discontinuation sub-study, will be followed at regular intervals over 3 years after randomization to develop a predictive model of risk to relapse to opioid use over time. Predictor variables will include duration and type of MOUD, demographic and clinical characteristics, features of the clinical course, and phenotyping and biomarkers.

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