Baclofen is a promising drug for treating patients with alcohol-related disorders. Nevertheless, the first randomized clinical trials (mainly with target doses), reported inconsistent efficacy, possibly because of the effective dose widely varying between patients. The Bacloville study aimed to test the efficacy of titrated baclofen for achieving low-risk alcohol consumption. 12-month multicenter pragmatic double-blind randomized clinical trial from June 2012 to June 2014. 62 French primary care centers. Outpatients with high-risk alcohol consumption (>40 g/day for women and >60 g/day for men). Patients were randomly assigned (1:1 ratio) to receive titrated baclofen up to 300 mg/day or placebo for 12 months. Switching to open-label baclofen was allowed in cases of perceived inefficacy. The primary outcome defined success as no or low-risk alcohol consumption (≤20 g/day for women and ≤40 g/day for men) during the last month of the one-year follow up, with patients who switched to open-label baclofen classified as failures. 320 patients were randomized, 162 to baclofen and 158 to placebo (consumption 129 g/day in both arms). Discontinuation rates were 30% and 34% in the baclofen and placebo arms, respectively, and return rates of the last-month diaries were 42% and 34% respectively. Primary success rates were 57% and 36% in the baclofen and placebo arms, respectively (difference 21 percentage points, 95% CI 8 to 34, p=0.003). When switchers were not classified as failures unless they did fail, the success rates were 62% versus 55% (difference 6 percentage points, 95% CI -7 to 20). Over 12 months, daily consumption differed between both arms (11 g less in the baclofen arm), as did the number of abstinence days (3.3 days more in the baclofen arm). Adverse events were more frequent with baclofen than placebo and were mostly drowsiness, fatigue and insomnia. Serious adverse events occurred in 85 (7 deaths) and 36 (3 deaths) patients with baclofen and placebo, respectively. Baclofen was more effective than placebo in reducing alcohol consumption to low-risk levels. The number of adverse events and more serious adverse events was greater with baclofen than placebo.

中文翻译：

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用于高风险饮酒的滴定巴氯芬：一项对门诊患者进行一年随访的随机安慰剂对照试验

巴氯芬是一种用于治疗酒精相关疾病患者的有前途的药物。然而，第一个随机临床试验（主要是目标剂量）报告了不一致的疗效，可能是因为有效剂量在患者之间差异很大。Bacloville 研究旨在测试滴定的巴氯芬对实现低风险饮酒的功效。2012 年 6 月至 2014 年 6 月的 12 个月多中心实用双盲随机临床试验。62 个法国初级保健中心。高危饮酒的门诊患者（女性>40 克/天，男性>60 克/天）。患者被随机分配（1:1 的比例）接受 300 毫克/天的滴定巴氯芬或安慰剂治疗 12 个月。在感觉无效的情况下，允许改用开放标签的巴氯芬。主要结局将成功定义为在一年随访的最后一个月没有或低风险饮酒（女性≤20 克/天，男性≤40 克/天），患者转为开放标签巴氯芬归类为失败。320 名患者被随机分配，162 名接受巴氯芬，158 名接受安慰剂（双臂每天消耗 129 克）。巴氯芬组和安慰剂组的停药率分别为 30% 和 34%，上个月日记的返回率分别为 42% 和 34%。巴氯芬组和安慰剂组的主要成功率分别为 57% 和 36%（差异 21 个百分点，95% CI 8 至 34，p=0.003）。当转换者不被归类为失败者除非他们确实失败时，成功率为 62% 对 55%（差异 6 个百分点，95% CI -7 到 20）。超过 12 个月，两组之间的每日消耗量不同（巴氯芬组少 11 克），禁欲天数也不同（巴氯芬组多 3.3 天）。与安慰剂相比，巴氯芬的不良事件更频繁，主要是困倦、疲劳和失眠。使用巴氯芬和安慰剂的患者分别发生了 85 例（7 例死亡）和 36 例（3 例死亡）严重不良事件。巴氯芬在将饮酒量降至低风险水平方面比安慰剂更有效。与安慰剂相比，巴氯芬的不良事件和更严重的不良事件数量更多。使用巴氯芬和安慰剂的患者分别发生了 85 例（7 例死亡）和 36 例（3 例死亡）严重不良事件。巴氯芬在将饮酒量降至低风险水平方面比安慰剂更有效。与安慰剂相比，巴氯芬的不良事件和更严重的不良事件数量更多。使用巴氯芬和安慰剂的患者分别发生了 85 例（7 例死亡）和 36 例（3 例死亡）严重不良事件。巴氯芬在将饮酒量降至低风险水平方面比安慰剂更有效。与安慰剂相比，巴氯芬的不良事件和更严重的不良事件数量更多。