Search the Library

This is the primary outcomes paper for CTN-0101.

Background and aims:
Individuals who engage in illicit or nonmedical opioid use may have elevated risk of health and social consequences, including progression to opioid use disorder (OUD). Preventive interventions to reduce this risk are lacking. This trial tested the impact of a primary care-integrated collaborative care approach for reducing risky opioid use, defined as nonmedical use of prescription opioids or any use of illicit opioids.

Design: Cluster-randomized controlled trial randomized primary care providers (PCPs) and their patients into the Subthreshold Opioid Use Disorder Prevention (STOP) intervention or enhanced usual care (EUC).

Setting: Primary care clinics at 5 U.S. sites.

Participants:
PCPs and their patients were recruited January 2021–May 2023. A total of 119 PCP clusters (STOP=48, EUC=51) and 202 patients (STOP=88, EUC=114) enrolled. Eligible patients were adults (≥18 years) having current risky opioid use, without moderate–severe OUD. Patient participants were majority female (63.4%), white (70.8%) and non-Hispanic (96.5%), with a mean age of 55.7 [standard deviation (SD) = 12.7] years. At baseline, 63.4% of participants had moderate–severe pain (Brief Pain Inventory) and below average physical (79.2%) and mental (62.4%) health (SF-12).

Interventions: The STOP collaborative care intervention consisted of brief advice from the PCP about reducing risky opioid use, meetings with a clinic-embedded nurse care manager over 12 months and remote health coaching (2–6 sessions). Both groups received primary care treatment as usual and overdose risk reduction materials.

Measurements: The primary outcome was total days of risky opioid use, recorded from 6 monthly electronic surveys. A key secondary outcome was moderate–severe OUD at 6 and 12 months.

Findings: A total of 77 (87.5%) STOP and 107 (93.9%) EUC participants completed the 6-month assessment period. The primary outcome analysis used the Intention-to-Treat sample with multiple imputations of missing data. Mean days of risky opioid use at 180 days were lower in STOP than EUC [12.2 (SD = 27.73) vs. 15.5 (SD = 32.64)]; the difference between groups adjusted for baseline risky opioid use was not statistically significant (rate ratio 0.95, 95% confidence interval = 0.52–1.74). One STOP participant (1.1%) and 13 EUC participants (11.4%) developed moderate–severe OUD at 6 months, and 3 (3.4%) STOP and 6 (5.3%) EUC participants had moderate–severe OUD at 12 months (P<0.001).

Conclusions: This cluster-randomized controlled trial did not find evidence that the STOP intervention for reducing risky opioid use produced greater reductions over 6 months compared with enhanced usual care, though fewer intervention participants progressed to moderate–severe opioid use disorder. Patients had a high burden of pain and comorbidities that may present challenges to reducing opioid use.

Related protocols: CTN-0101

Background: A majority of the 8.9 million Americans with opioid misuse have mild or no symptoms of opioid use disorder (OUD), but they may be at elevated risk of developing more severe OUD, overdose, or other health consequences of opioid use. The “Subthreshold Opioid Use Disorder Prevention”(STOP) Trial is evaluating a collaborative care intervention for risky opioid use in primary care. Here, we describe baseline characteristics of participants to understand their needs and assess the generalizability of the sample.

Methods: Recruitment at five primary care sites spanned March 2021-May 2023. Adult patients who screened positive for subthreshold OUD (current illicit or non-medical opioid use without meeting DSM-5 criteria for moderate-severe OUD) were eligible. Baseline assessments measured self-reported demographic characteristics, other substance use, pain, and physical and mental health symptoms. Descriptive statistics summarize characteristics of the enrolled sample across sites.

Results: Among the 202 participants, the majority identified as female (63.4%), white (70.8%), and non-Hispanic (96.5%), with mean age 55.7 (SD: 12.7) years. Nearly half (49.0%) had problem or high-risk use of prescription opioids, and most received a prescription for opioid medication in the past six months (74.8%). Many participants reported current problem use or high-risk use of alcohol (47.0%) or cannabis (31.2%). Approximately one-third endorsed mental health symptoms, including moderate-severe anxiety (35.6%), depression (31.2%), or sleep disturbance (29.7%), and 20.3% reported a past suicide attempt. In the prior six months, 14.7% had experienced a nonfatal overdose. Moderate-severe pain was reported by 63.4%, and 60.4% rated their general health as fair or poor.

Conclusions: Patients with subthreshold OUD had high rates of polysubstance use and comorbidities that may present challenges to reducing risky opioid use. The STOP trial presents an opportunity to detect and address subthreshold OUD in a cohort with considerable medical and social needs, within primary care settings.

Related protocols: CTN-0101

Preventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD.

The STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180 days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups using an intent-to-treat population.

Conclusions: Given a growing interest in interventions for the management of patients with risky opioid use, and the need for primary care-based interventions, this study potentially offers a blueprint for a feasible and effective approach to improving outcomes in this population.

Related protocols: CTN-0101

The application of digital technologies to better assess, understand, and treat substance use disorders (SUDs) is a particularly promising and vibrant area of scientific research. The National Drug Abuse Treatment Clinical Trials Network (CTN), launched in 1999 by the U.S. National Institute on Drug Abuse, has supported a growing line of research that leverages digital technologies to glean new insights into SUDs and provide science-based therapeutic tools to a diverse array of persons with SUDs.

This article provides an overview of the breadth and impact of research conducted in the realm of digital health within the CTN. This work has included the CTN’s efforts to systematically embed digital screeners for SUDs into general medical settings to impact care models across the nation. This work has also included a pivotal multi-site clinical trial conducted on the CTN platform, whose data led to the very first “prescription digital therapeutic” authorized by the U.S. Food and Drug Administration (FDA) for the treatment of SUDs. Further CTN research includes the study of telehealth to increase capacity for science-based SUD treatment in rural and under-resourced communities. In addition, the CTN has supported an assessment of the feasibility of detecting cocaine-taking behavior via smartwatch sensing. And, the CTN has supported the conduct of clinical trials entirely online (including the recruitment of national and hard-to-reach/under-served participant samples online, with remote intervention delivery and data collection). Further, the CTN is supporting innovative work focused on the use of digital health technologies and data analytics to identify digital biomarkers and understand the clinical trajectories of individuals receiving medications for opioid use disorder (OUD).

This paper concludes by outlining the many potential future opportunities to leverage the unique national CTN research network to scale-up the science on digital health to examine optimal strategies to increase the reach of science-based SUD service delivery models both within and outside of healthcare.

Related protocols: CTN-0044, CTN-0059, CTN-0073-Ot, CTN-0076, CTN-0083, CTN-0084-A-2, CTN-0090, CTN-0095, CTN-0101, CTN-0102