• Jenny G Low, Cynthia Sung, Limin Wijaya, Yuan Wei, Abhay P S Rathore, Satoru Watanabe, Boon Hian Tan, Liying Toh, Lian Tee Chua, Yan'an Hou, Angelia Chow, Shiqin Howe, Wing Ki Chan, Kah Hin Tan, Jasmine S Chung, Benjamin P Cherng, David C Lye, Paul A Tambayah, Lee Ching Ng, John Connolly, Martin L Hibberd, Yee Sin Leo, Yin Bun Cheung, Eng Eong Ooi, and Subhash G Vasudevan.
• Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore.
• Lancet Infect Dis. 2014 Aug 1;14(8):706-15.

BackgroundDengue 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.MethodsTo 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.FindingsWe 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.InterpretationAlthough generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with dengue.FundingSTOP Dengue Translational Clinical Research.Copyright © 2014 Elsevier Ltd. All rights reserved.

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