Table 1 Summary of CTN trials relevant to the RDD study

Studies on detoxification

 Ling et al. 2005 (CTN-0001)

12 sites, 113 adult OUD in-patients

OUD individuals seeking short-term inpatient treatment were randomly assigned, in a 2:1 ratio favoring buprenorphine-naloxone, to a 13-day detoxification using open label buprenorphine-naloxone or clonidine

77% of in-patients assigned to the buprenorphine-naloxone condition achieved success compared to 22% of patients assigned to clonidine (p = 0.05)

 Ling et al. 2005 (CTN-0002)

12 sites, 231 adult OUD outpatients

OUD individuals seeking outpatient treatment were randomly assigned, in a 2:1 ratio favoring buprenorphine-naloxone, to a 13-day detoxification using open label buprenorphine-naloxone or clonidine

46 of the 157 (29%) outpatients assigned to the buprenorphine-naloxone condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine (p = 0.05)

 Ling et al. 2009 (CTN-0003)

11 sites, 516 adult OUD outpatients

Compared open label buprenorphine short (7 day) or long (28 day) taper schedules after a 1-month stabilization phase

At the end of the taper 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; p = 0.0007). There were no differences at the 1-month and 3-month follow-ups

 Woody et al. 2008 (CTN- 0010)

6 sites, 152 OUD outpatients age 15–21

Patients were randomized to either 12-weeks of buprenorphine-naloxone (up to 24 mg per day for 9 weeks and tapered over weeks 10–12) or to a 14-day buprenorphine-naloxone detoxification

Individuals assigned to 12 weeks of buprenorphine (n = 78) showed significantly lower rates of positive urine toxicology for opioids at weeks 4 (61% vs 26% p < .001) and 8 (54% vs 23% (p = 0.01)) compared to individuals assigned to detoxification (n = 74) (. At week 12 the groups did not differ significantly (p = 0.18)

Studies on long-term maintenance outcomes

 Saxon et al. 2012 (CTN-0027)

8 sites, 1,269 adult OUD outpatients

Patients presenting for outpatient treatment were randomized to 24 weeks of open label flexible dosed buprenorphine-naloxone or methadone

There were no significant differences in medications for liver impact

Individuals assigned to methadone (n = 529) were significantly more likely (p < 0.0001) to have remained in treatment through week 24 (74% vs 46%) compared to those assigned to buprenorphine-naloxone (n = 740)

 Hser et al. 2016 (CTN-0050)

7 sites, 1080 participants of the CTN-0027 trial

Patients were followed up 2–8 years after randomization the initial CTN-0027 study

Patients self-reported opioid use and treatment status and provided a urine toxicology test and an oral rapid HIV test

Overall mortality was similar between buprenorphine (5.8%) and methadone (3.6%) participants (P = 0.10). Opioid use at follow up was higher among participants randomized to buprenorphine (42.8%) compared to methadone (31.7%) (p < 0.01). Both buprenorphine-naloxone and methadone were associated with lower opioid use compared to no treatment. More individuals who achieved long-term abstinence from both heroin and other opioids were in treatment compared to the non-treatment group (63.5% vs 50.9%)

 Weiss et al. 2011 (CTN-0030)

10 sites, 653 prescription OUD patients

Randomized two-phase clinical trial using an adaptive treatment research design to determine efficacy buprenorphine-naloxone with different counseling intensities for patients on prescription opioids

Phase 1: Brief treatment (phase 1) 2-week buprenorphine-naloxone stabilization, 2-week taper, 8-week post medication follow up randomized to either standard medical management (SMM) or standard medical management + opioid dependence counseling (SMM + ODC)

Phase 2: Those who did not meet study-defined success outcome during phase 1 were restarted on 12 weeks of buprenorphine-naloxone treatment (without taper) and again provided either SMM or SMM + ODC

Phase 1: only 6.6% of patients met study-defined outcomes for successful treatment. There was no significant difference (p = 0.39) in outcomes between SMM and SMM + ODC

Phase 2: 49.2% met study-defined criteria for success; there was no significant difference (p = 0.21) in outcomes between SMM and SMM + ODC

A history of ever using heroin was associated with lower phase 2 success rates

 Weiss et al. 2015 (CTN-0030a-3)

375 patients out of the 653 patients from the CTN-0030 study enrolled in a 42-month follow up study

Telephone interviews were administered at 18, 30, and 42 months after trial enrollment

At month 42: 31.7% were abstinent from opioids and not on agonist therapy. 29.4% were on agonist therapy, but not dependent on opioids. 7.5% were using illicit opioids while on agonist therapy. 31.4% were using opioids without agonist therapy

Lifetime heroin use was associated with opioid dependence at 42 months (p < 0.05). Agonist therapy was associated with greater likelihood of illicit opioid abstinence

 Campbell et al. 2014 (CTN-0044)

10 sites, 507 patients with various substance use disorders, including individuals with OUD (n = 108) but no patients on medication for OUD

Adults entering outpatient treatment were randomized to 12 weeks of treatment as usual or 12 weeks of treatment as usual and Therapeutic Education System (the therapeutic education system)

The therapeutic education system consisted of 62 computer interactive modules with financial incentives

The therapeutic education system reduced dropout rate (p = 0.01) and increased abstinence rates (p = 0.01) by nearly double in individuals with non-opioid substance use disorders

Individuals with OUD did not show improvement with the addition of the therapeutic education system

 Lee et al. 2018 (CTN-0051)

8 sites, 570 adult OUD patients, recruited on inpatient detoxification and residential units

Patients were randomized to either extended-release naltrexone (injectable naltrexone) OR sublingual buprenorphine-naloxone for outpatient maintenance treatment

Significantly fewer (p < 0.0001) individuals initiated XR—NTX (n = 204, 72%) vs buprenorphine-naloxone (n = 270, 94%)

Among patients successfully inducted, 24-week relapse rates were similar (p = 0.44)