Addiction Treatment in Russia:Oral and Depot Naltrexone

描述（由申请人提供）：在俄罗斯，海洛因成瘾的通常治疗包括戒毒和2-4周的康复，并转介到门诊随访。虽然大多数患者完成了住院治疗，但很少有人继续随访，复发率很高。需要更有效的治疗，特别是鉴于海洛因成瘾的流行已导致艾滋病毒和其他传染病的传播。最近完成的一项对52名随机接受口服纳洛酮（ON）或口服纳洛酮安慰剂（ONP）的患者的研究显示了预防复发和降低HIV风险的疗效，但脱落是一个问题，只有44%的ON患者被证明在6个月内没有复发，而ONP患者为16%。一项280例随机分配至ON或ONP（有或无氟西汀）组患者的大型研究将进一步评估这些早期结果，并确定添加SSRI是否会改善结局。本研究的招募工作已接近完成，但尚未完成，尚未获得结局数据。 我们认为贮库型注射用纳洛酮（DIN）也可以改善保留和结果，在这项研究中，我们建议比较ON与DIN。DIN未被批准在俄罗斯使用，我们希望这项研究的结果能够被俄罗斯当局接受，他们可能会批准其用于一般用途。因此，我们提出了一个安慰剂对照，双盲/双模拟设计，因为安慰剂对照试验是我们的FDA的俄罗斯等效要求作为批准药物治疗的条件。参与者将是在彼得堡成瘾治疗医院戒毒的男性和女性海洛因成瘾者，他们有一名家庭成员愿意并能够监督药物依从性并促进随访。 在给予知情同意书并确认不存在生理依赖性后，300名患者将被随机分配到三组中的一组进行6个月的治疗，每组100名：口服纳洛酮（ON）+长效注射纳洛酮安慰剂（DINP）;口服纳洛酮安慰剂（ONP）+长效注射纳洛酮（DIN）;或ONP + DINP。所有患者将接受每两周一次的临床管理/依从性增强咨询。 将在基线、6个月药物治疗期间每两周一次的预约以及药物治疗结束后3个月和6个月进行评估。主要结局将是第1-6个月的无复发比例;次要结局将是至脱落的时间、阿片类药物阳性尿液、HIV风险、酒精和其他药物的使用、精神症状和其他总体调整措施。 我们假设，结果将是更好的DIN比ON，每一个将比安慰剂更有效。

DESCRIPTION (provided by applicant): The usual treatment of heroin addiction in Russia involves detoxification and 2-4 weeks of rehabilitation with referral to outpatient follow-up. Though most patients complete inpatient treatment, few keep follow-up appointments and relapse rates are high. More effective therapies are needed, especially in view of the epidemic of heroin addiction that has resulted in the spread of HIV and other infectious diseases. A recently completed study of 52 patients randomized to oral naltrexone (ON) or oral naltrexone placebo (ONP) has shown efficacy in preventing relapse and reducing HIV risk but dropout was a problem with only 44% of ON patients proven to have not relapsed by 6 months as compared to 16% of ONP patients. A larger study of 280 patients randomized to ON or ONP with or without fluoxetine will further evaluate these early results and determine if adding a SSRI improves outcome. Recruitment into this study is almost completed but is not finished and outcome data are not yet available. We think that retention and outcome can be also improved by depot injectable naltrexone (DIN), and in this study we propose to compare ON with DIN. DIN is not approved for use in Russia and we would like the results of this study to be acceptable to Russian authorities that might approve it for general use. Thus we propose a placebo-controlled, double-blind/double-dummy design since a placebo-controlled trial is required by the Russian equivalent of our FDA as a condition for approval of a pharmacotherapy. Participants will be male and female heroin addicts who have been detoxified in addiction treatment hospitals in St. Petersburg and have a family member willing and able to supervise medication compliance and facilitate follow-up. After giving informed consent and confirming the absence of physiologic dependence, 300 patients will be randomly assigned to a 6-month treatment in one of three groups of 100 each: oral naltrexone (ON) + depot injectable naltrexone placebo (DINP); oral naltrexone placebo (ONP) + depot injectable naltrexone (DIN); or ONP + DINP. All patients will receive biweekly clinical management/compliance enhancement counseling. Assessments will be done at baseline, at each biweekly appointment during the 6-month of medication treatment, and at 3 and 6 months following the end of the medication. Primary outcome will be the relapse free proportion at months 1-6; secondary outcomes will be time to dropout, opioid positive urines, HIV risk, use of alcohol and other drugs, psychiatric symptoms, and other measures of overall adjustment. We hypothesize that outcomes will be better with DIN than ON, and that each will be more effective than placebo.