Extrait

Background and study aims Dengue is a mosquito-transmitted viral infection that represents a major public health problem in Vietnam and globally. The consequences range from a symptom-free infection through to life-threatening shock and bleeding. Severe dengue infection is often caused by inflammation of the lining of blood vessels (the endothelium). There is currently no treatment for dengue beyond supportive care. Lovastatin is part of a class of drugs called statins, which were initially developed as fat (lipid)-lowering agents but have been shown to have additional benefits. Studies suggest that their use appears to be associated with an improved outcome in critically ill patients. The additional benefits include reducing inflammation of the endothelium, which could translate into a beneficial effect in dengue. Furthermore, laboratory studies have shown that lovastatin may have additional antiviral properties. These properties together with its favourable safety and cost profile make lovastatin an attractive option for dengue treatment. The main aim of the study is to formally assess the safety of using statins in patients with dengue. The study will also provide an opportunity to investigate the effect of statins on the immune response to dengue, the dengue viral load and the clinical outcome of infection. Who can participate? All patients aged 18 or over with a clinical suspicion of dengue, less than 72 hours of fever and a positive rapid test for dengue non-structural protein 1 (NS1) will be eligible for recruitment into the study. We have a target sample size of 330 patients. What does the study involve? We propose to investigate the effect of lovastatin for 5 days in adult dengue patients presenting in the first 72 hours of illness. Patients will be randomly allocated to one of two groups: one group will take lovastatin and the other group will take a dummy drug (placebo). As this is the first study investigating statin therapy in dengue with a particular focus on safety, we will use a low dose of lovastatin with the first 30 patients. If this is found to be safe we will then increase the lovastatin dose for the next 30 patients. What are the possible benefits and risks of participating? This is the first study exploring the use of statins in dengue. In view of this, our study has a particular emphasis on safety. Statins are very widely used and have an excellent safety profile. Rarely they can cause potentially serious problems with muscles and the liver. It is possible that these effects may occur more often in patients with dengue. We will therefore closely monitor patients to detect the development of adverse events early. In addition, patients may experience discomfort and bruising from the blood tests, although these would form part of the usual care for patients infected with dengue. The study will pay the participants' hospital costs. If lovastatin has a beneficial effect this will potentially benefit the patients taking lovastatin as well as future patients, and will potentially benefit the community given the prevalence of dengue in Vietnam. Where is the study run from? The Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. When is the study starting and how long is it expected to run for? Patients will be recruited over two dengue seasons (2012 and 2013). The study started in November 2012 and is expected to end in January 2015. Who is funding the study? The Wellcome Trust (UK) Who is the main contact? Dr James Whitehorn [email protected]

Critère d'inclusion

• Dengue disease

Liens

• isrctn
• ictrp