An alternative analysis of illicit opioid use during treatment in a randomized trial of extended-release naltrexone versus buprenorphine-naloxone: A per-protocol and completers analysis.

Background: The distinct pharmacological properties and clinical uses of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) present challenges in analyzing patient outcomes.

Methods: We conducted a secondary analysis of a multi-site randomized trial comparing XR-NTX with sublingual BUP-NX treatment for opioid use disorder initiated during inpatient detoxification and continued in outpatient treatment. Urine testing data for non-study opioids from the last 22 weeks of the 24-week trial were analyzed in both a per-protocol sample (n = 474 participants who received at least one dose of medication) and a completers sample (n = 211 participants who received all XR-NTX doses or all BUP-NX prescriptions). The present analyses sought to identify differences in the weekly percentages of opioid-positive urine tests between participants treated with the two medications.

Results: The proportion of opioid-positive tests in both conditions was less than 20 % for 21 of the 22 weeks in the per-protocol sample and all 22 weeks in the completers sample. Generalized linear mixed model analyses revealed a significant treatment (XR-NTX vs. BUP-NX) X week (weeks 3-24) interaction in the per-protocol sample but not the completers sample. In the per-protocol analysis, the BUP-NX, compared to XR-NTX, had significantly greater proportions of opioid-positive tests in 14 out of the 22 weeks.

Conclusions: Longitudinal modeling approaches that utilize flexible procedures for handling missing data can offer a different perspective on study findings. Results from the present analyses suggest that XR-NTX appeared to be somewhat more effective than BUP-NX in reducing illicit opioid use in the per-protocol sample.