Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial.
Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial.
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DOI：
10.1016/s1473-3099(14)70717-0
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发表时间：
2014-07
期刊：
影响因子：
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通讯作者：
US Nitazoxanide Influenza Clinical Study Group
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文献类型：
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作者：
Haffizulla J;Hartman A;Hoppers M;Resnick H;Samudrala S;Ginocchio C;Bardin M;Rossignol JF;US Nitazoxanide Influenza Clinical Study Group
流感是世界范围内发病率和死亡率的重要原因。治疗选择很少，需要具有新作用机制的新药。我们的目的是评价噻唑胺类抗感染药物硝唑尼特治疗急性无并发症流感的有效性和安全性。我们在2010年12月27日至2011年4月30日期间在美国74家初级保健诊所进行了一项双盲、随机、安慰剂对照的2b/3期试验。我们招募了12-65岁的受试者，他们在症状出现后48小时内有发烧，至少有一种呼吸道症状，以及一种流感的体征。我们随机分配参与者接受硝唑西尼600 mg、硝唑西尼300 mg或安慰剂每日两次(比例为1：1：1)治疗5天，并对他们进行28天的随访。随机化列表由计算机生成，三人一组完成。在这项研究中，赞助商、研究人员、研究监督员、患者和实验室人员都被掩盖了治疗分配。主要终点是从第一次服药到症状缓解的时间。初步分析是通过RT-PCR或基线培养确诊为流感感染的参与者的意向治疗。这项试验在ClinicalTrials.gov注册，编号NCT01227421。在650名筛选的参与者中，有624人(96%)入选。在这些人中，212人被随机分配到每天接受两次安慰剂治疗，201人每天接受300毫克的治疗，211人每天接受600毫克的治疗。服用安慰剂的受试者症状持续时间的中位数为116·7h(95%可信区间108·1-122·1)，而服用600 mg硝唑尼特的受试者为95·5h(84·0-108·0；p=0.0084)，服用300 mg硝唑尼特的受试者为109·1h(96·1-129·5，p=0.52)。三组之间的不良事件相似，最常见的是安慰剂组212名患者中的24名(11%)报告的头痛，低剂量组的12名(6%)，以及高剂量组211名患者中的17名(8%)，或腹泻，由7名(3%)的安慰剂组患者，4名(2%)的低剂量组患者和17名(8%)的高剂量组患者报告。硝唑尼特每日两次，每次600毫克，连续5天治疗，与急性无并发症流感患者症状持续时间的缩短有关。有必要进行进一步的研究，以证实这些发现，并评估该药物单独或与现有药物联合使用对重病患者和有流感并发症风险的患者的疗效。罗马克实验室有限公司。
Influenza is an important cause of morbidity and mortality worldwide. Treatment options are scarce, and new drugs with novel mechanisms of action are needed. We aimed to assess the efficacy and safety of nitazoxanide, a thiazolide anti-infective, for treatment of acute uncomplicated influenza. We did a double-blind, randomised, placebo-controlled, phase 2b/3 trial in 74 primary care clinics in the USA between Dec 27, 2010, and April 30, 2011. We enrolled participants aged 12–65 years with fever, at least one respiratory symptom, and one constitutional symptom of influenza within 48 h of symptom onset. We randomly assigned participants to receive either nitazoxanide 600 mg, nitazoxanide 300 mg, or placebo twice daily for 5 days, (ratio 1:1:1) and followed them up for 28 days. Randomisation lists were computer generated and done in blocks of three. Sponsor, investigators, study monitors, patients, and laboratory personnel were all masked to treatment allocation in the study. The primary endpoint was the time from first dose to alleviation of symptoms. The primary analysis was by intention-to-treat for participants with influenza infection confirmed by RT-PCR or culture at baseline. This trial is registered with ClinicalTrials.gov, number NCT01227421. Of 650 participants screened, 624 (96%) were enrolled. Of these, 212 were randomly assigned to receive placebo twice a day, 201 to receive nitazoxanide 300 mg twice a day, and 211 to receive nitazoxanide 600 mg a day. The median duration of symptoms for participants receiving placebo was 116·7 h (95% CI 108·1–122·1) compared with 95·5 h (84·0–108·0; p=0·0084) for those receiving 600 mg nitazoxanide and 109·1 h (96·1–129·5, p=0·52) for those receiving 300 mg nitazoxanide. Adverse events were similar between the three groups, the most common being headache reported by 24 (11%) of 212 patients enrolled in placebo group, 12 (6%) of 201 patients in the low-dose group, and 17 (8%) of 211 patients in the high-dose group, or diarrhoea, reported by seven (3%) patients in the placebo group, four (2%) patients enrolled in the low-dose group, and 17 (8%) patients in the high-dose group. Treatment with nitazoxanide 600 mg twice daily for 5 days was associated with a reduction of the duration of symptoms in participants with acute uncomplicated influenza. Further studies are warranted to confirm these findings and to assess efficacy of the drug alone or in combination with existing drugs in seriously ill patients and those at risk of influenza complications. Romark Laboratories LC.