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CTRI Number  CTRI/2024/04/066302 [Registered on: 25/04/2024] Trial Registered Prospectively
Last Modified On: 24/03/2025
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Preventive 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Restricted vs liberal intravenous fluid administration in preterm newborns less than 1 Kilogram 
Scientific Title of Study   Restricted versus conventional fluid administration in Extremely Low Birth Weight neonates: A randomised control non-inferiority trial 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Anitha Haribalakrishna 
Designation  Associate Professor and Incharge (Head) 
Affiliation  Seth GSMC and KEM Hospital Mumbai 
Address  Department of Neonatology New building, 10th Floor Seth GSMC and KEM Hospital Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  9769660870  
Fax    
Email  ani.gem81@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Anitha Haribalakrishna 
Designation  Associate Professor and Incharge (Head) 
Affiliation  Seth GSMC and KEM Hospital Mumbai 
Address  Department of Neonatology New building, 10th Floor Seth GSMC and KEM Hospital Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  9769660870  
Fax    
Email  ani.gem81@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Anitha Haribalakrishna 
Designation  Associate Professor and Incharge (Head) 
Affiliation  Seth GSMC and KEM Hospital Mumbai 
Address  Department of Neonatology New building, 10th Floor Seth GSMC and KEM Hospital Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  9769660870  
Fax    
Email  ani.gem81@gmail.com  
 
Source of Monetary or Material Support  
Department of Neonatology,New building, 10th floor, ward 38, Seth GS Medical College and KEM Hospital, Mumbai 
 
Primary Sponsor  
Name  Dr Anitha Haribalakrishna 
Address  Department of Neonatology, Seth GS Medical College and KEM Hospital 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Anitha Haribalakrishna  Seth GS Medical College KEM Hospital  Department of Neonatology, New building, 10th floor, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012
Mumbai
MAHARASHTRA 
9769660870

ani.gem81@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee 3  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: P84||Other problems with newborn,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Comparitor group  Admission of standard fluid at the rate of 130ml/kg/day on day 1, followed by incrementing at the rate of 20ml/Kg/day till day 3, then incrementing at the rate of 10ml/Kg/day on day 4 and 5,giving fluid at the rate of 200ml/Kg/day from day 6. 
Intervention  restricted fluid   Administration of restricted fluid at the rate of 60ml/Kg/day on day 1, and incrementing at the rate of 20ml/Kg/day till day 5, followed by 150ml/Kg/day from day 6 onwards 
 
Inclusion Criteria  
Age From  1.00 Day(s)
Age To  28.00 Day(s)
Gender  Both 
Details  All extremely low birth weight neonates less than 1000
grams  
 
ExclusionCriteria 
Details  Neonates with major congenital anomaly 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome  
Outcome  TimePoints 
all cause mortality
 
4 weeks
 
 
Secondary Outcome  
Outcome  TimePoints 
Neonatal morbidities  During NICU stay or at discharge 
 
Target Sample Size   Total Sample Size="100"
Sample Size from India="100" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Post Marketing Surveillance 
Date of First Enrollment (India)   01/06/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - YES
  1. What data in particular will be shared?
    Response - All of the individual participant data collected during the trial, after de-identification.

  2. What additional supporting information will be shared?
    Response -  Study Protocol
    Response -  Statistical Analysis Plan
    Response - Informed Consent Form
    Response - Clinical Study Report

  3. Who will be able to view these files?
    Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.

  4. For what types of analyses will this data be available?
    Response - For individual participant data meta-analysis.

  5. By what mechanism will data be made available?
    Response - Proposals should be directed to [ani.gem81@gmail.com].

  6. For how long will this data be available start date provided 01-01-2025 and end date provided 01-02-2030?
    Response - Beginning 3 months and ending 5 years following article publication.

  7. Any URL or additional information regarding plan/policy for sharing IPD? 
    Additional Information - NA
Brief Summary
Modification(s)  

Extremely low birth weight babies contribute to a very small percentage of the total

number of admissions in the NICU but contribute a disproportionality high number

up to 27% of total mortality. Cochrane review comparing restricted and liberal fluid

management in neonates to prevent various morbidities has shown that following

restricted fluid management there was a reduction in the incidence of PDA and

Necrotising Enterocolitis (NEC) and a trend towards reduction in bronchopulmonary

dysplasia, intracranial hemorrhage and death. (4). In the same review, the total fluid

rate (TFR) in the first week of life ranged from a daily average of 60-80ml/kg/day

in the restricted fluid arm, and the liberal group, TFR was up to 160-180ml/kg/day. 

To assess the effect of restricted and liberal fluid regimens in ELBW infants admitted

in the neonatal intensive care unit (NICU) with the primary outcome being a reduction in

all cause mortality. Sample size of this RCT is 100 and to be conducted over 1 year.

All extremely low birth weight neonates(<1000 grams) will be included in the study. There are

Two study groups: Group A: restricted fluid management. Group B: Liberal fluid

management group. Blinding :This is an unblinded study since the as per

methodology, the study cannot be blinded. The fluid management in the enrolled participants would be done as follows based on their group of randomisation. Evnthough in the literature review, the initial fluid requirement on day 1 of life in the restricted arm is 60-80ml/kg/day, in this study,the fluid requirement has been proposed as 80-100ml/kg/day due to feasibility issues. 

Day of life

Restricted fluid(ml/kg/day)

Liberal fluid (ml/kg/day)

D1

80-100

120-130

D2

100-120

130-150

D3

120-140

150-170

D4

140-160

170 -180

D5

160-170

180-200

Maximum fluid volume

170

200

 During the study, the enrolled neonates will be monitored by:

Weight will be measured using an electronic weighing scale which will be

calibrated daily

Urine specific gravity- Urine will be collected using sterile bag/cotton, noninvasively

and a urine refractometer will be used for checking the specific

gravity

Serum Sodium, Creatinine and venous blood gas are obtained in the sample

report using 0.1ml of blood using ABG Analyser.

All of the above are routinely done for ELBW babies admitted to NICU, there

is no requirement for additional tests or there won’t be any additional

expenditure involved.

Maintenance intravenous fluids will be increased by 10ml10ml/kg/day in the

presence of any of the following in the restricted fluid arm:

1) Abnormal urine output ( <1ml/kg/hr or > 5ml/kg/hr) and urine-specific

gravity ( >1.018)

2) Weight loss of more than 1.5%-2% every 12hrly ( 3%-4% every 24hrly)

3) Serum creatinine of more than 1.5mg/dl or more than 1.5times the

baseline S. Creatinine

4) Serum Sodium of more than 160meq/dl.

5) VBG suggestive of Metabolic acidosis with pH <7.25, Hc03 < 16, Base

deficit >8-10 or lactate more than 4.

In neonates enrolled in the restrictive group will be changed over to liberal

group fluid as per the day-of-life if the fluid requirement is required to be

increased by 10ml/kg/day two times in 12 hrs. In both groups, if the neonate

develops hypovolemic shock, septic or cardiogenic shock fluid management

will be as per standard shock management. Rest of the management of neonates will be as per NICU protocol and study results will be analyzed using statistical

tests.

 
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