A MULTI CENTER DOUBLE-BLIND RANDOMIZED PARALLEL-GROUP PHASE III CLINICAL TRIAL ON EFFECTIVENESS OF DEXTRAN 40 COMPARED TO NORMAL SALINE IN PREVENTING DENGUE SHOCK IN EARLY LEAKAGE PHASE OF PATIENTS WITH DENGUE HEMORRHAGIC FEVER

INTERVENTION: Study setting Professorial medical units of Teaching Hospitals Anuradhapura and Peradeniya. Randomization method Permuted block randomization will be done by a person who is not part of the study. Varying block sizes will be used, and block sizes are blinded to investigators to avoid predictability. Intervention and control Infusion of 5ml/Kg (maximum 250ml) of dextran 40 over two hours during early critical phase of dengue haemorrhagic fever. This will be compared with 5ml/Kg (maximum 250ml) of normal saline infusion over two hours (standard/current practice). Participants will be randomized to receive dextran or normal saline when the urine output drops less than 0.5ml/Kg/hour for two hours. Reduction of urine output less than the minimum obligatory amount in a patient with dengue haemorrhagic fever is an important clinical feature. It indicates intravascular fluid depletion and possible pre‐renal acute kidney injury. Commercially available dextran 40 is dissolved in normal saline, therefore both groups will receive equal volumes of normal saline as a part of the study. The only difference between two groups is one group receiving five grams of Dextran 40 in addition to normal saline per dose. CONDITION: Dengue haemorrhagic fever PRIMARY OUTCOME: Reduction of proportion of compensated or uncompensated shock by 15% in the dextran group compared to control group; ; Compensated shock: Tachycardia with narrow pulse pressure (< 30mmHg), Decompensated shock: Systolic blood pressure less than 90mmHg and /or mean arterial pressure less than 65mmHg; ; ; [Calculated after leakage phase (48 hour period)]; Proportion of patients with reduction of in pulse rate by 20% one hour after drug administration [ One hour after drug administration; ]; Proportion of patients with blood pressure improvement by 20% one hour after drug administration [ One hour after drug administration; ]; Proportion of patients with pulse pressure improvement by 20 % one hour after drug administration [ One hour after drug administration; ]; Proportion of patients with resolution of postural tachycardia at the end of the study drug administration. ‐ The pulse rate to come to baseline or to the lowest level ‐ whichever is lower; Postural tachycardia is rise of the pulse rate ; > 15 beats per min from the supine position to erect position (within 3‐5 min) at the time of examination.; ; Baseline for postural tachycardia is resting pulse rate at lying position when the patient is euvolemic and afebrile [ One hour after drug administration]; Proportion of patients with improved urine output i.e more than 0.5ml/Kg/hour [The first measurement is one hour after study drug administration and hourly thereafter for 48 hrs or end of leaking phase.]; SECONDARY OUTCOME: Duration of maintenance of normal urine output (> 0.5ml/kg) after study drug administration ; [One hourly after study drug administration for 48 hours]; Percentage change of inferior vena cava (IVC) diameter post drug administration ; [ One hour after drug administration ]; Amount of total fluid needed to maintain haemodynamic stability over the critical phase [Calculated at the end of the leaking phase]; Number of rescue fluid boluses needed over 1st, 2nd, 3rd and 4th twelve‐hour periods, post study drug administration. [ 1st, 2nd, 3rd and 4th twelve‐hour periods, post study drug administration. ]; INCLUSION CRITERIA: 1. All male and female patients 2. Aged 18 and above 3. Diagnosed with dengue fever