Opium tincture versus methadone for opioid agonist treatment: a randomized controlled trial

Aim To test if opium tincture (OT) was non-inferior to methadone in retaining participants in opioid agonist treatment (OAT). Design A Phase III, multi-centre, parallel-group, non-inferiority, double-blind randomized controlled trial with an allocation ratio of 1:1. Participants were provided treatment and followed for a period of 85 days. Setting Four OAT clinics in Iran. Participants Two hundred and four participants with opioid use disorder [mean age (standard deviation) = 37.4 (9.3); female 11.3%] recruited between July 2017 and January 2018. Interventions Participants were assigned to either OT (102) or methadone (102) using a patient-centred flexible dosing strategy. Measurements Treatment retention over 85 days was the primary outcome. Self-reported opioid use outside treatment and occurrence of adverse events (AEs) were the secondary outcomes. Findings Remaining in treatment at the end of the follow-up were 68.6% in the methadone arm and 59.8% in the OT arm. The relative retention rate of methadone to OT was 1.15 (0.97, 1.36) in both intent-to-treat and per-protocol analyses; non-inferiority was not supported statistically, as the upper bound of the confidence interval exceeded our pre-specified non-inferiority margin (1.25). Opioid use outside treatment was reported by 30.3% of OT (n = 152) and 49.4% of methadone (n = 168) patients, a difference in proportions of -19%: 90% confidence interval (-28%, -10%). The total count of AEs in the OT arm (22 among nine individuals) was significantly higher (P = 0.04) than that in the methadone arm (three among two individuals). Nausea was the most common side effect. Conclusion While this study could not conclude the non-inferiority of opium tincture (OT) to methadone for retaining patients in opioid agonist treatment, OT retained 60% of participants to end of follow-up (85 days) and was superior to methadone in reducing self-reported opioid use outside treatment.

Automated summary

This study aimed to compare the effectiveness of opium tincture (OT) and methadone in retaining participants in opioid agonist treatment (OAT). The results showed that OT retained 60% of participants to the end of the 85-day follow-up period and was superior to methadone in reducing self-reported opioid use outside of treatment. However, the study did not find sufficient evidence to conclude the non-inferiority of OT compared to methadone.