Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore.
Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore.
Lancet Infect Dis. 2014 Aug;14(8):706-715. doi: 10.1016/S1473-3099(14)70730-3. Epub 2014 May 28.
Dengue infection is the most common mosquito-borne viral disease worldwide, but no suitable antiviral drugs are available. We tested the α-glucosidase inhibitor celgosivir as a treatment for acute dengue fever.
To establish eligibility for inclusion in a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial, individuals aged 21-65 years who had had a fever (≥38°C) for less than 48 h, met at least two criteria indicating probable dengue infection, and had a positive result on a dengue point-of-care test kit or PCR assay were referred for screening at a centre in Singapore between July 30, 2012, and March 4, 2013. Using a web-based system, we randomly assigned patients who met full inclusion criteria after screening (1:1; random permuted block length four) to celgosivir (initial 400 mg loading dose within 6 h of randomisation, followed by 200 mg every 12 h for a total of nine doses) or matched placebo. Patients and the entire study team were masked to group assignment. The primary endpoints were mean virological log reduction (VLR) from baseline for days 2, 3, and 4, and area under the fever curve (AUC) for a temperature above 37°C from 0 h to 96 h. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01619969.
We screened 69 patients and randomly assigned 50 (24 to celgosivir, 26 to placebo). Mean VLR was greater in the celgosivir group (-1·86, SD 1·07) than in the placebo group (-1·64, 0·75), but the difference was non-significant (-0·22, 90% CI -0·65 to 0·22; one-sided p=0·203). The mean AUC was also higher in the celgosivir group (54·92, SD 31·04) than in the placebo group (40·72, 18·69), but again the difference was non-significant (14·20, 90% CI 2·16-26·25; one-sided p=0·973). We noted similar incidences of adverse events between groups.
Although generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with dengue.
STOP Dengue Translational Clinical Research.
登革热感染是全球最常见的蚊媒病毒性疾病，但目前尚无有效的抗病毒药物。我们检测了α-葡萄糖苷酶抑制剂昔洛韦作为急性登革热的治疗药物。
为了在 2012 年 7 月 30 日至 2013 年 3 月 4 日在新加坡的一个中心建立一项 1b 期、随机、双盲、安慰剂对照、概念验证试验的纳入资格，年龄在 21-65 岁之间、发热（≥38°C）时间不足 48 小时、符合至少两个提示可能为登革热感染的标准且登革热即时检测试剂盒或 PCR 检测结果阳性的个体被转诊进行筛查。使用基于网络的系统，我们对筛查后符合全部纳入标准的患者（1:1；随机区组长度为 4）进行分组，随机分配至昔洛韦组（随机分组后 6 小时内给予 400mg 初始负荷剂量，随后每 12 小时给予 200mg，共 9 剂）或匹配的安慰剂组。患者和整个研究团队对分组均不知情。主要终点是从基线开始第 2、3 和 4 天的平均病毒学对数减少（VLR）和从 0 小时到 96 小时的体温高于 37°C 的曲线下面积（AUC）。疗效分析采用意向治疗。本研究在 ClinicalTrials.gov 注册，编号为 NCT01619969。
我们筛查了 69 例患者，并随机分配了 50 例（24 例至昔洛韦组，26 例至安慰剂组）。昔洛韦组的平均 VLR（-1.86，SD 1.07）大于安慰剂组（-1.64，0.75），但差异无统计学意义（-0.22，90%CI-0.65 至 0.22；单侧 p=0.203）。昔洛韦组的 AUC 也高于安慰剂组（54.92，SD 31.04）（40.72，18.69），但差异同样无统计学意义（14.20，90%CI2.16-26.25；单侧 p=0.973）。我们注意到两组的不良反应发生率相似。
尽管昔洛韦通常安全且耐受良好，但似乎并不能降低登革热患者的病毒载量或发热负担。
终止登革热转化临床研究。
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