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Open Access Study protocol

Lovastatin for adult patients with dengue: protocol for a randomised controlled trial

James Whitehorn12*, Nguyen Van Vinh Chau23, Nguyen Thanh Truong3, Luong Thi Hue Tai3, Nguyen Van Hao3, Tran Tinh Hien2, Marcel Wolbers24, Laura Merson24, Nguyen Thi Phuong Dung2, Rosanna Peeling1, Cameron Simmons24, Bridget Wills24 and Jeremy Farrar24

Author Affiliations

1 Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK

2 Hospital for Tropical Diseases Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam

3 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

4 Centre for Tropical Medicine, University of Oxford, Oxford, UK

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Trials 2012, 13:203  doi:10.1186/1745-6215-13-203

Published: 31 October 2012

Abstract

Background

Dengue is the most important vector-borne viral infection of man, with approximately 2 billion people living in areas at risk. Infection results in a range of manifestations from asymptomatic infection through to life-threatening shock and haemorrhage. One of the hallmarks of severe dengue is vascular endothelial disruption. There is currently no specific therapy and clinical management is limited to supportive care. Statins are a class of drug initially developed for lipid lowering. There has been considerable recent interest in their effects beyond lipid lowering. These include anti-inflammatory effects at the endothelium. In addition, it is possible that lovastatin may have an anti-viral effect against dengue. Observational data suggest that the use of statins may improve outcomes for such conditions as sepsis and pneumonia. This paper describes the protocol for a randomised controlled trial investigating a short course of lovastatin therapy in adult patients with dengue.

Methods/design

A randomised, double-blind, placebo-controlled trial will investigate the effects of lovastatin therapy in the treatment of dengue. The trial will be conducted in two phases with an escalation of dose between phases if an interim safety review is satisfactory. This is an exploratory study focusing on safety and there are no data on which to base a sample size calculation. A target sample size of 300 patients in the second phase, enrolled over two dengue seasons, was chosen based on clinical judgement and feasibility considerations. In a previous randomised trial in dengue, about 10% and 30% of patients experienced at least one serious adverse event or adverse event, respectively. With 300 patients, we will have 80% power to detect an increase of 12% (from 10% to 22%) or 16% (from 30% to 46%) in the frequency of adverse events. Furthermore, this sample size ensures some power to explore the efficacy of statins.

Discussion

The development of a dengue therapeutic that can attenuate disease would be an enormous advance in global health. The favourable effects of statins on the endothelium, their good safety profile and their low cost make lovastatin an attractive therapeutic candidate.

Trial registration

International Standard Randomised Controlled Trial Number ISRCTN03147572

Keywords:
Clinical trial; Dengue; Lovastatin; Statins