Addiction 2016;111(8):1416-1427. [doi: 10.1111/add.13375]
Walter Ling, MD (Integrated Substance Abuse Programs (ISAP), UCLA, PR Node), Maureen Hillhouse, PhD (ISAP, UCLA, PR Node), Andrew J. Saxon, MD (VA Puget Sound Health Care System, PN Node), Larissa J. Mooney, MD (ISAP, UCLA, PR Node), Christie Thomas, MPH (ISAP, UCLA, PR Node), Alfonso Ang, PhD (ISAP, UCLA, PR Node), Abigail G. Matthews, PhD (Data & Statistics Center (DSC), EMMES Corporation), Albert Hasson, MSW (ISAP, UCLA, PR Node), Jeffrey J. Annon, MA, MISM (ISAP, UCLA, PR Node), Steven Sparenborg, PhD (NIDA Center for the Clinical Trials Network (CCTN)), David S. Liu, MD (NIDA CCTN), Jennifer McCormack, MS (DSC, EMMES Corporation), Sarah Church, PhD (Albert Einstein College of Medicine of Yeshiva University, GNY Node), William Swafford, MD (Addiction Research and Treatment Services, ), Karen Drexler, MD (VA Medical Center Atlanta, SC Node), Carolyn Schuman, MD (BAART San Mateo, PR Node), Stephen Ross, MD (New York University School of Medicine, GNY Node), Katharina L. Wiest, PhD (CODA Inc., WS Node), P. Todd Korthuis, MD, MPH (Oregon Health & Science University, WS Node), William Lawson, MD (Howard University), Gregory S. Brigham, PhD (Maryhaven Treatment Center, WS Node), Patricia C. Knox, PhD (Recovery Centers of King County, PN Node), Michael Dawes, MD (South Texas Veterans Health Care System, TX Node), John Rotrosen, MD (New York University School of Medicine, GNY Node).
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. (Article (Peer-Reviewed), PDF, English, 2016)
Keywords: Buprenorphine/Naloxone | Cocaine | Cognitive behavioral therapy (CBT) | CTN primary outcomes | Naltrexone | Pharmacological therapy | Suboxone | Addiction (journal)
Document No: 1195, PMID: 26948856, PMCID: PMC4940267 (available 8/1/2017).
Submitted by CTN Dissemination Librarians, 3/17/2016.