Methadone Induction in Primary Care for Opioid Dependence: A Pragmatic Randomized Trial (ANRS Methaville)

ObjectiveMethadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC.MethodsIn this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively.ResultsIn the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively).ConclusionsUnder appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence.Trial registrationNumber Eudract 2008-001338-28; ClinicalTrials.gov: NCT00657397; International Standard Randomized Controlled Trial Number Register ISRCTN31125511【研究目的】美沙酮（methadone）在全球多国的覆盖范围仍存在不足，部分原因在于美沙酮诱导治疗仅能在专科医疗（specialized care, SC）机构开展。本项多中心实用性临床试验，对比了初级医疗（primary care, PC）与专科医疗两种美沙酮诱导模式的治疗效果。 【研究方法】本研究已于ClinicalTrials.gov注册（注册号：NCT00657397）。研究纳入对象为：至少1个月未接受美沙酮治疗的阿片类物质依赖者，或正在接受丁丙诺啡（buprenorphine）治疗但需更换治疗方案的患者。所有受试者按随机分配原则，被纳入法国10个研究中心的初级医疗组（n=155）或专科医疗组（n=66），启动美沙酮诱导治疗。随访节点设定为基线（M0）、第3个月（M3）、第6个月（M6）及第12个月（M12）。主要结局指标为第12个月时自我报告的街头阿片类物质戒断情况，研究预设初级医疗组非劣效界值为15%。次要结局指标包括随访期间的戒断情况、治疗依从性（即完成诱导疗程）、治疗保留率及患者对医师诊疗解释的满意度。主要分析采用意向性治疗（intention to treat, ITT）原则；分别采用混合效应模型与对数秩检验（log-rank test），评估两组（初级医疗组vs专科医疗组）对戒断病程与治疗保留率的干预效应。 【研究结果】意向性治疗分析共纳入初级医疗组155例、专科医疗组66例。对比两组受试者街头阿片类物质戒断率，初级医疗组第12个月时戒断率为55%（85/155），专科医疗组为33%（22/66）；该分析证实初级医疗组的非劣效性（差值为21.5%，95%置信区间：7.7%~35.3%）。初级医疗组的治疗依从性与患者对医师解释的满意度均显著高于专科医疗组。两组的美沙酮治疗保留率及随访期间戒断率均无显著差异（分别对应p=0.47与p=0.39）。 【研究结论】在适宜条件下，初级医疗环境下开展美沙酮诱导治疗具备可行性，且同时获得医师与患者的认可。该模式在减少街头阿片类物质使用、保障阿片类物质依赖者的治疗依从性与保留率方面，效果与专科医疗诱导模式相当。 【试验注册】Eudract注册号：2008-001338-28；ClinicalTrials.gov注册号：NCT00657397；国际标准随机对照试验注册库编号：ISRCTN31125511