Determining the Optimum Dose, Efficacy and Safety of an Ayurvedic Formulation, Link Natural Sudarshana (LNS) in Patients with Dengue, Randomised, Double-blinded, Placebo Controlled Phase II Clinical Trial

INTERVENTION: Study setting: The study will be conducted at the National Institute of Infectious Diseases (NIID), Angoda. Patients who visit the OPD of the NIID and diagnosed with dengue, confirmed by a positive NS1 antigen, will be invited to participate in the study. A leaflet containing a brief introduction about the study will be distributed among the patients. Volunteer participants who fulfill the inclusion criteria will be recruited to the study. Randomization: Simple randomization method using computer‐generated random numbers Blinding: Neither participants, nor investigators, nor data collectors nor the study team nor data analysts will be aware of treatment assignments prior to the final breaking of codes of data base. The code of database will be opened after completion of data analysis and conclusion of the study. Intervention: Two doses of treatment and placebo tablets will be packed into identical white HDPE (High Density Polyethylene) plastic bottles numbered from 1 to 240 by a senior R&D Scientist (Pharmacist) at Link Natural Products (Pvt.) Ltd. according to the list of computer‐generated random numbers provided by the statistician. The label of each bottle will indicate only the patient’s random number and the directions for taking the tablets. Each bottle will contain 60 tablets needed for the whole duration of treatment of 10 days. The patients will be treated according to the current Dengue guidelines published by the Ministry of Health, Sri Lanka. The patients who fulfil the admission criteria will be admitted to the ward while other patients who do not need admission will be managed as OPD patients following National Dengue Management Guideline. Patients in three groups (two test doses and placebo) will be instructed to take a dose of two tablets of LNS or p CONDITION: Dengue PRIMARY OUTCOME: The proportion of dengue patients who progress into critical phase.; Evidence of plasma leakage will be considered as: detection of free fluid in the abdomen or by the presence of a pleural effusion by an ultrasound (US) scan or by the presence of a rise in haematocrit of >20% of the baseline. [FBC will be done twice daily, Clinical assessments will be carried out at least 3 times a day until discharge]; SECONDARY OUTCOME: 1. Average Duration of the illness: The first day of the illness will be defined as the day in which the patient developed fever. The day of recovery will be defined when all three following criteria are fulfilled: ; ; 1.a Improvement in clinical status (general well‐being, appetite, haemodynamic status, urine output, no respiratory distress determined by a medical investigator at NIID who is blinded to the investigation arm of the patient (placebo or IMP). Further the recruited OPD patients will be advised to come to the OPD for daily assessment as per usual practice at NIID and at the OPD medical investigator at NIID will assess the criterion. He/she is blinded to the investigation arm of the patient (placebo or IMP).; ; 1.b Increasing trend in the platelet count as measured by a minimum of 2 readings ; ; 1.c Stable haematocrit without intravenous fluids [Baseline and FBC will be done twice daily after intervention, Clinical assessments will be carried out at least 3 times a day until discharge.FBC and clinical assessment will be carried out daily in the outpatient setting until recovery; ; ; ; ; ; ]; 2. Change of liver enzymes (AST and ALT), prothrombin time and serum creatinine from baseline to day 10. [Baseline to day 5 & 10 from intervention]; c) Change of cumulative symptom score from baseline to day 10.; The 15 symptoms assessed would be fever, headache, joint pain, muscle pain, rashes, nausea, vomiting, loss of appetite, sleep disturbances, malaise (lack of wellbeing), fatigue (extreme tiredness), abdominal pain, restlessness, sweating, dizziness. Each symptom will be scored daily by the patient as absent (score 0), mild (1), moderate (2) or severe (3). [ Baseline and daily unitl? [for OPD?]]; d) Average fatigability score at day 15, 30, 45 and 60 assessed using using validated Chalder Fatigue questionnaire [at day 15, 30, 45 and 60 [from what?]]; b) Change of liver enzymes (AST and ALT), prothrombin time and serum creatinine . [ Baseline, Day 5 and day 10 [?]]; c) Change of cumulative symptom score from baseline to day 10.; The 15 symptoms assessed would be fever, headache, joint pain, muscle pain, rashes, nausea, vomiting, loss of appetite, sleep disturbances, malaise (lack of wellbeing), fatigue (extreme tiredness), abdominal pain, restlessness, sweating, dizziness. Each symptom will be scored daily by the patient as absent (score 0), mild (1), moderate (2) or severe (3). [ Baseline and daily]; d) Average fatigability score at day 15, 30, 45 and 60 assessed using Chalder Fatigue questionnaire.; Fatigability will be assessed using validated Chalder Fatigue questionnaire [ On day 15, 30, 45 and 60]; c) Change of cumulative symptom score from baseline to day 10.; The 15 symptoms assessed would be fever, headache, joint pain, muscle pain, rashes, nausea, vomiting, loss of appetite, sleep disturbances, malaise (lack of wellbeing), fatigue (extreme tiredness), abdominal pain, restlessness, sweating, dizziness. Each symptom will be scored daily by the patient as absent (score 0), mild (1), moderate (2) or severe (3). [ Baseline and daily]; d) Average fatigability score at day 15, 30, 45 and 60 assessed using Chalder Fatigue questionnaire.; Fatigability will be assessed using validated Chalder Fatigue questionnaire [Baseline, on day 15, 30, 45 and 60]; b) Change of liver enzymes (AST and ALT), prothrombin time and serum creatinine from baseline to day 10. [ Baseline, Day 5 and day 10]; c) Change of cumulative symptom score from baseline to day 10.; The 15 symptoms assessed would be fever, headache, joint pain, muscle pain, rashes, nausea, vomiting, loss of appetite, sleep disturbances, malaise (lack of wellbeing), fatigue (extreme tiredness), abdominal pain, restlessness, sweating, dizziness. Each symptom will be scored daily by the patient as absent (score 0), mild (1), moderate (2) or severe (3). [ Baseline and daily]; d) Average fatigability score at day 15, 30, 45 and 60 assessed using Chalder Fatigue questionnaire.; Fatigability will be assessed using validated Chalder Fatigue questionnaire [Baseline, on day 15, 30, 45 and 60]; INCLUSION CRITERIA: • Laboratory evidence of Dengue: All Patients with confirmed dengue infection by a positive dengue NS1 antigen detection test and confirmed by PCR test. The dengue NS1 antigen will be done by rapid immunochromatographic assays (rapid strip tests at the OPD). Those who provides informed written consent and who fulfil all of the following criteria will be recruited. • Age: between 18‐70 * Both male and female • Duration of illness: Equal or less than 48 hours of the onset of fever