Buprenorphine-naloxone plus naltrexone for the treatment of cocaine dependence: The Cocaine Use Reduction with Buprenorphine (CURB) study.

This is the primary outcomes article for CTN-0048.

This study aimed to examine the safety and effectiveness of buprenorphine+naloxone sublingual tablets (BUP, as Suboxone) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the NIDA Clinical Trials Network (CTN-0048), randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York, and Washington D.C. to 1 of 3 conditions provided with XR-NTX: 4mg/day BUP (BUP4, n=100), 16mg/day BUP (BUP16, n=100), or no buprenorphine (placebo, PLB, n=102).

Participants received pharmacotherapy for 8 weeks, with 3 clinic visits per week. Cognitive Behavioral Therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention, and adverse events.

No group differences were found between groups for the primary outcome (BUP4 vs. PLB, p=0.262; BUP16 vs PLB, p=0.185).). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB (p=0.022, OR=1.71) but not for BUP4 (p=0.105, OR=1.05). No secondary outcome differences across groups were found for adherence, retention, or adverse events.

Conclusions: Although the primary outcome analysis did not detect significant differences in cocaine use between treatment groups, some urine drug screen analyses found that participants randomized to higher dose (16 mg/day) of buprenorphine provided significantly more cocaine-negative urine samples compared to participants randomized to placebo. Furthermore, the medication combination used in this study appeared to be safe with little risk of inducing iatrogenic opioid dependence. The combination of naltrexone and buprenorphine deserves further confirmatory study as pharmacotherapy for cocaine use disorder.

Related protocols: CTN-0048