Oseltamivir for treatment of thrombocytopenia and plasma leakage in dengue

INTERVENTION: The study is designed as a phase 2, multicentre, randomized, placebo‐controlled, double‐blinded intervention trial. Participants will be randomized using block randomization in a 1:1 allocation ratio. The trial is double‐blinded, i.e. both researchers/study personnel, physicians and participants are blinded. The intervention tested is oseltamivir phosphate 75mg BID orally (intervention group) or placebo (control group) until platelet number reaches >100 x 10^9/L or for a maximum of 5 days. Patients are randomised using block randomization with variable block size. Platelet numbers are determined 2 times/daily in all participants and plasma leakage are assessed daily using ultrasonography and by twice daily haematocrit. Participants will be followed up daily until discharge from hospital or until their platelet count has reached = 100 x 109/l. A follow‐up visit at home will be performed three weeks after randomization to assess for late complications and to obtain convalescence laboratory measurements. CONDITION: Dengue ; Infections and Infestations ; Dengue PRIMARY OUTCOME: 1. Time to platelet recovery (platelet count = 100 x 109/l) is measured using twice daily platelet count measurement from enrollment until discharge or until platelet count = 100 x 109/l; 2. Plasma leakage is measured by twice daily haematocrit and daily ultrasonography (looking for gall bladder wall thickness, ascites and pleural fluid) from enrollment until discharge or until platelet count = 100 x 109/l ; ; SECONDARY OUTCOME: 1. Safety of oseltamivir use in dengue is measured using daily measurement of creatinine and liver enzymes from enrollment until discharge or until platelet count =100 x 109/l for a maximum of five days and at week 3 post‐enrollment; 2. Rate of change of platelet count is measured twice daily using platelet count measurement at 24, 48 and 5 days; 3. Number of participants developing severe thrombocytopenia measured using platelet count measurement at enrollment until discharge or until platelet count = 100 x 109/l. ; 4. Dengue‐related complications, especially clinical bleeding is assessed daily using WHO bleeding scores at enrollment until discharge or until platelet count = 100 x 109/l; 5. Flow cytometric platelet studies, including platelet activation and reactivity assays as well as platelet sialic acid expression is measured daily using antibodies against P‐selectin and the binding of fibrinogen to platelets in unstimulated samples and after stimulation with platelet agonists. Platelet sialic acid content is measured using the lectins SNA, MAL‐II and RCA.; 6. Markers of inflammation, coagulation and endothelial perturbation is measured using daily plasma samples INCLUSION CRITERIA: 1. Admission to hospital 2. Aged 18 years and above 3. Positive result of NS1 rapid test (proven dengue) or positive for acute dengue serology with probable dengue criteria as defined in WHO 2009 criteria 4. Fever <=6 days 5. Platelet count <70 x 10^9/L