Effect of enteral melatonin on invasive fungal infection and antifungal susceptibility profile in critically ill sepsis patients: A prospective randomized control trial

effect of melatonin will be studied on incidence of fungal infections

Methodology in detail The patients admitted to ICU within 2 days of admission and will be allotted bed in an alternate manner in both the ICUs or wherever beds will be available Nursing staff who will be advised to give either of blinded drugs study drug in group A, placebo In group B as per following dose Then nursing staff will be advised to give tab melatonin 5mg around 9pm along with usual medications followed by 5mg every 1 hour 5mg+5mg+5mg total =20mg PO daily If one patient will be admitted after 12am then next day around at 9pm drug will be given but if patient admitted within 9pm to 12 am then drug will be given as early as possible within 12 am and next dose will be given as usual as other patients dose at around 9pm through ryles tube daily This process will be continued till the patient is admitted or till complication developed in the patient due to study drugs or expiry of the patient ,whichever is early. The required data variables will be collected by a blinded resident doctor

The study population will contain 2 groups 1. Group A where patients will be given the study drug melatonin 20mg in form of 4 doses of 5mg tablets every 1 hourly through ryles tube

2. Group B where patients will be given placebo 20mg in form of 5mg every hourly for 4 times everyday through ryles tube till icu stay or death

PRIMARY OUTCOME • Incidence of invasive fungal infections fungal sepsis & septic shock. • Susceptibility profile in form of MIC values of antifungal drugs.

SECONDARY OUTCOME • Total days free of antifungal therapy • Incidence of bacterial sepsis and septic shock . • Susceptibility profile of bacterial agents and use of antibacterial agents . • Ventilator free days. • Length of ICU stay . • vasopressor use. • Outcome sepsis and septic shock reversal, death).

The sample size is 92, taking population proportion as 89 percent a confidence level of 95 percent and a margin of error of 5 percent .Considering a dropout percentage of 10 percent, we aim for a total sample size of 120

Participants will be followed up daily while on the ICU. Routinely collected clinical data cardiovascular, respiratory and renal physiological variables as well as haematological, biochemical parameters will be recorded on a daily basis. Microbiological blood test including bacterial culture, fungal culture, galactomannan, B 1,3 glucan results along with MIC values of the antifungal agents will be collected during the study period as per protocol till 28th day of ICU stay or death, whichever is earlier. Patients will also be followed up to ascertain survival status at 28 days post recruitment and at hospital discharge.