Abstract
BackgroundDengue 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/designA 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.DiscussionThe 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 registrationInternational Standard Randomised Controlled Trial Number ISRCTN03147572
Highlights
Dengue is the most important vector-borne viral infection of man, with approximately 2 billion people living in areas at risk
The development of a dengue therapeutic that can attenuate disease would be an enormous advance in global health
Clinical dengue varies from asymptomatic infection to severe disease characterised by shock and haemorrhage
Summary
Dengue remains a significant global public health challenge with costs to both the infected individual and the struggling health systems of dengue-endemic countries. A therapeutic that can attenuate disease and prevent progression to severe disease would represent a highly significant advance with enormous benefits for both patients and health systems. There is growing observational evidence from the critical care field to suggest that statins may have a beneficial role in a number of conditions, such as sepsis, acute lung injury and pneumonia. As endothelial dysfunction is so important in dengue pathogenesis, stabilizing effects at this site may prove to be clinically beneficial. The role of the data and safety monitoring board (DSMB) An independent DSMB will be set up consisting of a biostatistician and senior clinical researchers with expertise in dengue and clinical trials. The DSMB will review the protocol and agree to a data review schedule and reporting requirements before the study commences.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
