CTRI Number	CTRI/2017/10/010255 [Registered on: 30/10/2017] Trial Registered Retrospectively
Last Modified On:	30/10/2017
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Medical Device
Study Design	Randomized, Parallel Group, Placebo Controlled Trial
Public Title of Study Modification(s)	“various causes of hyponatremia and its relation to seizures and outcome in patients with acute febrile encephalopathy in neurology intensive care unit (NICU)”.
Scientific Title of Study Modification(s)	“Etiology of hyponatremia, its relation to seizures and outcome in acute febrile encephalopathy – A prospective study in neurology intensive care unit (NICU) patients”.
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)	Name  Dr U K Misra  Address  Dept. of Neurology, C-Block, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Raebarely Road, Lucknow, UP Lucknow UTTAR PRADESH 226014 India  Phone  0522-2494167   Fax  0522-2668811   Email  drukmisra@rediffmail.com
Details Contact Person Scientific Query	Name  Dr U K Misra  Address  Dept. of Neurology, C-Block, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Raebarely Road, Lucknow, UP Lucknow UTTAR PRADESH 226014 India  Phone  0522-2494167   Fax  0522-2668811   Email  drukmisra@rediffmail.com
Details Contact Person Public Query	Name  Dr U K Misra  Address  Dept. of Neurology, C-Block, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Raebarely Road, Lucknow, UP Lucknow UTTAR PRADESH 226014 India  Phone  0522-2494167   Fax  0522-2668811   Email  drukmisra@rediffmail.com
Source of Monetary or Material Support Modification(s)	SGPGIMS, raibarreley road, lucknow,Uttar-pradesh PIN-226014
Primary Sponsor	Name  Sanjay Gandhi Postgraduate Institute of Medical Sciences   Address  Sanjay Gandhi Postgraduate Institute of Medical Sciences   Type of Sponsor  Research institution
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 1   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr U K Misra  Sanjay Gandhi Postgraduate Institute of Medical Sciences   ROOM NO: G- BLOCK, 7 th FLOOR,A and B ward, Dept. of Neurology. Lucknow   05222494167 0522-2668811 drukmisra@rediffmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 1   Name of Committee  Approval Status  SGPGI, Institutional Ethics Committee  Approved
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied	Health Type  Condition  Patients  patients diagnosed as acute encephalitic syndrome. no comorbidities like uncontrol hypertension, liver failure renal failure, pregnancy, lactation
Intervention / Comparator Agent	Type  Name  Details  Intervention  fludrocortisone  Patients will receive fludrocortisone tablet (0.1 – 0.4 mg once daily)along with intravenous fluids (preferably normal saline) and oral salt supplementation (5 gm/ day). Fludrocortisone will be started at a dose of 0.1 mg once daily in the morning and will be increased every third day with an increment of 0.1 mg till primary outcomes are achieved or total dose of 0.4 mg once daily has been reached.   Comparator Agent  intravenous fluids (preferably normal saline) and oral salt supplementation (5 gm/ day)with placebo  the patients in control arm will be treated with intravenous fluids (prefrebaly normal saline and oral salt supplementation (5 gm/ day)along with visually similar placebo for the same duration as with the active arm
Inclusion Criteria Modification(s)	Age From  10.00 Year(s) Age To  80.00 Year(s) Gender  Both  Details  All patients with fever and altered sensorium within 10 days of their illness.
ExclusionCriteria	Details  children <15years, pregnant and lactating women, malaria, septic, fungal and carcinomatous meningitis, head injury, stroke, tumors, malignancy, chronic renal failure, hepatic failure, Heart failure, Other secondary causes of hyponatremia (drugs, diuretics).
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	Other
Blinding/Masking	Participant and Investigator Blinded
Primary Outcome	Outcome  TimePoints  No of days required to correct sodium to 135 meq/L.  1 month
Secondary Outcome	Outcome  TimePoints  Dose of fludrocortisone required to reach primary outcome. No. of patients developing intolerance to fludrocortisone (hypertension, hypokalemia). Seizures due to hyponatremia. Disability at discharge, 3 and 6 months based on modified Barthel index and m RS score. Mortality at 28 days, 3 months and 6 months. Residual deficits in terms of seizures, cognitive, cranial nerve and motor deficits at the end of 6 months   1 month
Target Sample Size	Total Sample Size="60" Sample Size from India="60"
Phase of Trial	Phase 4
Date of First Enrollment (India) Modification(s)	03/10/2015
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Open to Recruitment
Publication Details	not yet
Brief Summary	Hyponatremia in patients with AES including TB meningitis is multifactorial. It may be due to poor intake, extra renal loss due to recurrent vomiting (raised intracranial pressure) or drug induced. Cerebral salt wasting and SIADH are other common but unrecognized causes of hyponatremia in such patients. Cerebral salt wasting syndrome is characterized by natriuresis, hyponatremia and volume contraction in response to cerebral pathology. Correct management of hyponatremia is crucial for good outcome. Hyponatremia due to CSW is often difficult to treat. IV fluids, oral salt supplementation are the standard treatment options for the treatment of hypo-natremia associated with CSW. However, saline and oral salt supplementation does not address the primary pathology of excessive urinary sodium excretion. Fludrocortisone is a mineralocorticoid which acts on distal convoluted tubules and collecting ducts and helps in renal sodium absorption and passive water reabsorption. This leads to correction of hyponatremia and volume repletion. Fludrocortisone will be tried as an “add on therapy” over the usual standard care. This prospective randomized control study will investigate the efficacy and safety of  fludrocortisone along with IV Fluids and oral salt supplementation in comparison to the usual standard care (IV Fluids and oral salt supplementation) alone.