Edward V Nunes1, Adam Bisaga1, Evgeny Krupitsky2,3, Narinder Nangia4, Bernard L Silverman4, Sarah C Akerman4, Maria A Sullivan1,4. 1. New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, USA. 2. St Petersburg Pavlov State Medical University, St Petersburg, Russia. 3. Department of Addictions, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, St Petersburg, Russia. 4. Alkermes, Inc., Waltham, MA, USA.
Abstract
BACKGROUND AND AIMS: Extended-release formulations of naltrexone have emerged as effective treatment options for opioid use disorder. This post-hoc analysis examined the temporal relationship between episodes of opioid use and subsequent dropout in a placebo-controlled trial of extended-release injection naltrexone (XR-NTX) to draw inferences about the mechanism by which extended blockade of opioid receptors translates into clinical effectiveness. DESIGN: This was a 24-week multiple-site, double-blind, randomized trial of monthly XR-NTX versus placebo injections. We analyzed time to dropout from treatment using survival analysis with an extended Cox model as a function of treatment (XR-NTX versus placebo) and with weekly urine drug test (UDT) results for opioids at each week as a time-dependent covariate. SETTING:Thirteen addiction treatment programs in Russia, 2008-09. PARTICIPANTS: A total of 250 adults with opioid use disorder who had completed in-patient detoxification. INTERVENTION: XR-NTX injection or placebo injection every 4 weeks with weekly clinic visits and biweekly counseling. MEASUREMENTS: Urine toxicology for opioids measured weekly and week of dropout from treatment. FINDINGS: The Cox model yielded a significant interaction of time-dependent urine toxicology by treatment (P = 0.024). Among patients receiving placebo, a positive UDT in a given week increased the risk for dropout from treatment in the subsequent week [hazard ratio (HR) = 6.25; 95% confidence interval (CI) = 3.6-10.0], whereas among patients receiving XR-NTX, a positive UDT result showed no significant effect on risk for dropout (HR = 1.67; 95% CI = 0.6-4.5). The proportion of patients who completed all 24 weeks without any positive UDT result was 31% on XR-NTX compared with 20% on placebo (P = 0.051). CONCLUSIONS: Extended-release injection naltrexone was effective at reducing the risk of dropout from opioid use disorder treatment after an episode of opioid use. Just under a third of patients (31%) on XR-NTX had no opioid-positive urine tests across the trial, but the hypothesis that this would differ from placebo (20%) was not confirmed.
RCT Entities:
BACKGROUND AND AIMS: Extended-release formulations of naltrexone have emerged as effective treatment options for opioid use disorder. This post-hoc analysis examined the temporal relationship between episodes of opioid use and subsequent dropout in a placebo-controlled trial of extended-release injection naltrexone (XR-NTX) to draw inferences about the mechanism by which extended blockade of opioid receptors translates into clinical effectiveness. DESIGN: This was a 24-week multiple-site, double-blind, randomized trial of monthly XR-NTX versus placebo injections. We analyzed time to dropout from treatment using survival analysis with an extended Cox model as a function of treatment (XR-NTX versus placebo) and with weekly urine drug test (UDT) results for opioids at each week as a time-dependent covariate. SETTING: Thirteen addiction treatment programs in Russia, 2008-09. PARTICIPANTS: A total of 250 adults with opioid use disorder who had completed in-patient detoxification. INTERVENTION: XR-NTX injection or placebo injection every 4 weeks with weekly clinic visits and biweekly counseling. MEASUREMENTS: Urine toxicology for opioids measured weekly and week of dropout from treatment. FINDINGS: The Cox model yielded a significant interaction of time-dependent urine toxicology by treatment (P = 0.024). Among patients receiving placebo, a positive UDT in a given week increased the risk for dropout from treatment in the subsequent week [hazard ratio (HR) = 6.25; 95% confidence interval (CI) = 3.6-10.0], whereas among patients receiving XR-NTX, a positive UDT result showed no significant effect on risk for dropout (HR = 1.67; 95% CI = 0.6-4.5). The proportion of patients who completed all 24 weeks without any positive UDT result was 31% on XR-NTX compared with 20% on placebo (P = 0.051). CONCLUSIONS: Extended-release injection naltrexone was effective at reducing the risk of dropout from opioid use disorder treatment after an episode of opioid use. Just under a third of patients (31%) on XR-NTX had no opioid-positive urine tests across the trial, but the hypothesis that this would differ from placebo (20%) was not confirmed.
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