Extrait

Background and study aims Cryptococcal meningitis (CM) causes around 625,000 deaths every year, most of which occur within 3 months of diagnosis. It is the leading cause of death in HIV patients in Asia and Africa. The incidence in these regions is the highest in the world - in Africa, it is estimated there are more deaths due to CM than due to tuberculosis. There has been no major advance in the treatment of CM since the 1970s. The main drugs used to treat CM (amphotericin B and flucytosine) are over 50 years old, and they are often poorly available where the disease burden is highest. While effective antifungal therapy is key, adjunctive treatments, which have been seen to have dramatic effects on death rates in other nervous system infections, are untested in CM. Given the high death rates in patients receiving the best current treatment and the lack of new drugs on the horizon, adjuvant treatments offer the greatest potential to reduce death rates in CM. Dexamethasone is a cheap, readily available and practical treatment. This study aims to find out whether adding dexamethasone to standard antifungal therapy reduces death rates in CM. Who can participate? Patients who are more than 18 years of age, HIV-positive and have CM can participate in the study. What does the study involve? Eligible participants will randomly be allocated to one of two groups: the dexamethasone group or the dummy drug (placebo) group. The dexamethasone dose will depend on the participant’s body weight and the dose will be reduced each week. All patients will also receive antifungal treatment consisting of 2 weeks of amphotericin B combined with high-dose fluconazole, followed by fluconazole alone for 8 weeks (10 weeks in total). Patients will be in hospital for at least 2 weeks and then followed-up until week 10 and if possible to 6 months. What are the possible benefits and risks of participating? It is unknown if the participants in the dexamethasone group will benefit from the treatment. The additional monitoring and follow-up of patients by dedicated study staff may be of benefit to patients treated in resource-limited settings. The study results will help us to understand how to best treat CM and it may help others with this disease in the future. This study will use a drug that has been studied thoroughly and its toxicities are well known. Blood and cerebral spinal fluid will be taken for research tests. These volumes have very little risk of affecting the participant's health. This procedure carries a small risk of bruising and infection. Dexamethasone may be suppress growth in children and fetuses. Therefore, children and pregnant women have been excluded from this study. Where is the study run from? Vietnam, Indonesia, Thailand, Laos, Uganda and Malawi When is the study starting and how long is it expected to run for? It started in September 2012 and it should run for about three years Who is funding the study? The Department for International Development, the Wellcome Trust and the Medical Research Council in the UK Who is the main contact? Dr Jeremy Day [email protected]

Critère d'inclusion

• Cryptococcus meningitis/HIV

Liens

• isrctn
• ictrp