CTRI

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CTRI Number

CTRI/2026/01/101386 [Registered on: 16/01/2026] Trial Registered Prospectively

Last Modified On:

15/01/2026

Post Graduate Thesis

Yes

Type of Trial

Interventional

Type of Study

Process of Care Changes

Study Design

Randomized, Parallel Group, Active Controlled Trial

Public Title of Study

A Clinical Trial on the Effect of Fluid Management on ventilator requirements among Extremely Premature babies

Scientific Title of Study

Effect of Fluid restriction and Fluid balance targeting in early postnatal period on Respiratory Outcomes in Preterm infants born less than 29 weeks of Gestation. A Randomized Controlled 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	Haribalakrishna Balasubramanian
Designation	Neonatologist
Affiliation	Surya Childrens Medicare Pvt. Ltd.
Address	Department of Neonatology, 4th Floor, Surya Hospitals, S.V. Road, Santacruz West. Mumbai (Suburban) MAHARASHTRA 400054 India
Phone	02261538911
Fax
Email	doctorhbk@gmail.com

Details of Contact Person
Scientific Query

Name	Tellis Jessica Sebastian
Designation	Senior Resident in Neonatology
Affiliation	Surya Childrens Medicare Pvt. Ltd.
Address	Department Of Neonatology, 4th Floor, Surya Hospitals, S.V. Road, Santacruz West. Mumbai (Suburban) MAHARASHTRA 400054 India
Phone	02261538911
Fax
Email	tellis.jessica@gmail.com

Details of Contact Person
Public Query

Name	Tellis Jessica Sebastian
Designation	Senior Resident in Neonatology
Affiliation	Surya Childrens Medicare Pvt. Ltd.
Address	Department of Neonatology, 4th Floor, Surya Hospitals, S.V. Road, Santacruz West. Mumbai (Suburban) MAHARASHTRA 400054 India
Phone	02261538911
Fax
Email	tellis.jessica@gmail.com

Source of Monetary or Material Support

Surya Childrens Medicare Pvt. Ltd.

Primary Sponsor

Name	Surya childrens medicare pvt. ltd
Address	Surya Childrens medicare pvt. ltd, S.V. road, Santacruz west, Mumbai 400054
Type of Sponsor	Private hospital/clinic

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 Haribalakrishna Balasubramanian	Surya Childrens Medicare Pvt. Ltd..	Department of Neonatology, 4th Floor, Surya Hospitals, S.V. Road, Santacruz West. Mumbai (Suburban) MAHARASHTRA	02261538911 doctorhbk@gmail.com

Details of Ethics Committee

No of Ethics Committees= 1
Name of Committee	Approval Status
Medical Ethics Committee-Clinical Research, Surya Childrens Medicare Pvt. Ltd.	Approved

Regulatory Clearance Status from DCGI

Status

Not Applicable

Health Condition / Problems Studied

Health Type	Condition
Patients	(1) ICD-10 Condition: P285\|\|Respiratory failure of newborn,

Intervention / Comparator Agent

Type	Name	Details
Intervention	Fluid restriction	Fluids will be started at 100-120 ml/kg/day (less than 27 weeks), and 80 ml/kg/day (27 to 29 weeks). Fluid increments will be done by 10ml/kg every day till maximum fluid intake of 150ml/kg/day. Maximum enteral feed volume for this group will be targeted to 170ml/kg/day. Total Fluid intake in the first 2 weeks of age will be targeted according to fluid balance chart specific to this group.
Comparator Agent	Non-restriction of fluids	Fluids will be started at 100-120 ml/kg/day (less than 27 weeks), and 80 ml/kg/day (27 to 29 weeks). Fluid increments will be done by 20ml/kg every day till maximum fluid intake of 170ml/kg/day. Maximum enteral feed volume for this group will be targeted to 190ml/kg/day. Total Fluid intake in the first 2 weeks of age will be targeted according to fluid balance chart specific to this group.

Inclusion Criteria

Age From	1.00 Day(s)
Age To	28.00 Day(s)
Gender	Both
Details	Infant born less than 29 weeks of gestation and needing mechanical ventilation at or shortly after birth, if on ventilatory support by 24 hours of age.

ExclusionCriteria

Details

1.Infants with major congenital surgical condition.
2.Infants with life threatening congenital genetic anomalies.
3. Infant with refractory shock resistant to inotropes and or steroids.
4. Small for gestational age babies less than 3rd percentile.
5. Out born infants admitted to NICU after 6hours of age.
7. Infants with arterial or venous hematocrit more than 65 percent in first 24 hours.

Method of Generating Random Sequence

Stratified block randomization

Method of Concealment

Sequentially numbered, sealed, opaque envelopes

Blinding/Masking

Open Label

Primary Outcome

Outcome	TimePoints
Duration of primary mechanical ventilation	four to six weeks of age

Secondary Outcome

Outcome	TimePoints
Fluid balance	until 14 days of age
Peak negative fluid balance	until 14 days of age
Total fluid intake	until discharge
Calorie and protein intake	until discharge
Total parenteral nutrition days	until discharge
Time of feed initiations	until discharge
Time to full enteral feeds	until discharge
Time to regain birth weight	until discharge
Weight gain during hospital stay	until discharge
Days of primary invasive ventilation	until discharge
Duration of secondary ventilation	until discharge
Days of NIMV	until discharge
Days of CPAP	until discharge
Days of Oxygen	until discharge
Rates of primary extubation failure	within 7 days of extubation
Rate of re-ventilation	within 28 days and until discharge
Days of positive pressure ventilation (NIPPV+ NIMV)	until discharge
pH, PaCo2, Mean airway rpessure and Fio2 trends	till 6 weeks of age
Neonatal morbidities. A. All cause Mortality B. Shock (requiring inotropes or steroids) C. IVH (grade 3 or more) (Volpe criteria) D. PDA (requiring treatment)	until discharge
E. Oliguria (urine output less than 1 ml/kg/h) F. Metabolic bone disease (presence of serum phosphorus less than 5.4 mg/dl and alkaline phosphate more than 900 IU/l), G. Hypotension (blood pressure below the 10th percentile for infants gestational age, postnatal age and weight) H. Hypoglycemia (Blood sugar levels less than 45mg/dl)	until discharge
I. Hyperglycemia (Blood sugar levels more than 200mg/dl) J. Hyperbilirubinemia K. Metabolic acidosis (pH less than 7.2) L. Hyponatremia less than 135 mEq/L, M. Severe hyponatremia less than 125 mEq/L N. Hypernatremia more than 145 mEq/L O. Severe hypernatremia more than 155mEq/L, P. Diuretic use and if used, age at start of diuretics and duration Q. Use of postnatal steroids	until discharge
R. NEC (definitive NEC) (modified Bells stage II or more) S. ROP (requiring intervention like laser or anti-VEGF) (ICROP), T. PVL (DeVries classification grade II or more) U. AKI – (increase in serum creatinine of more than equal to 0.3 mg/dL within 48 hours, or more than equal to 1.5 times the baseline level, within the prior seven days or urine output less than 0.5 ml/kg/h for 6–12 h)	until discharge

Target Sample Size

Total Sample Size="132"
Sample Size from India="132"
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

Phase 3

Date of First Enrollment (India)

01/02/2026

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="2"
Months="0"
Days="0"

Recruitment Status of Trial (Global)

Not Yet Recruiting

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

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

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

For what types of analyses will this data be available?
Response - To achieve aims in the approved proposal.

By what mechanism will data be made available?
Response (Others) - Data will be made available on reasonable request to the principal investigator at doctorhbk@gmail.com

For how long will this data be available start date provided 20-01-2028 and end date provided 20-01-2030?
Response (Others) - start date after 6 months of study completion and end date 2 years from start date

Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - NIL

Brief Summary

Introduction:

Fluid balance in early postnatal period plays a very important role in extreme preterm infants. Higher fluid balance leads to pulmonary edema, impaired oxygenation and increased ventilatory requirements. Studies have shown positive fluid balance in first 14 days, early birth weight regain and requirement of diuretics aare associated with mortality and increased mechanical ventilatory requirements. Fluid restriction in early postnatal life has shown to decrease incidence of bronchopulmonary dysplasia and Patent ductus arteriosus. However definitve evidence of fluid restriction in extreme preterm is lacking. Hence we hypothesised that fluid restriction and fluid balance tagreting in the first 2-4 weeks of age could reduce the need and/or duration of ventilation.

Methods:

Study infants will be started on parenteral nutrition-at 100-110 ml/kg/day (less than 27 weeks), and 80 ml/kg/day (27 to 29 weeks). At 24 hrs, fluid increments in both groups will proceed as described in the intervention and comparator section. Total parenteral nutrition intake will be optimized in both groups starting at 40-45 Kcal/kg/day, 2g/kg/day of protein, lipids of 2g/kg/day to maximum of 80Kcal/kg/day, 3.5-4g/kg/day of protein and lipids of 4g/kg/day from TPN alone.

Additional fluid intake adjustments will be titrated according to the fluid balance on the given day.

Fluid balance (FB) will be estimated as daily weight minus birth weight divided by birth weight multiplied by 100.

In both groups, fluid adjustments (increase or decrease) besides the mandatory fluid intakes will be managed according to a FB chart that was designed based on average fluid balance over the first 2 weeks in large cohorts of extremely premature infants <29 weeks of gestation.

Non-restricted fluid group

	Total fluid intake increase by 20 ml/kg/day	Total fluid intake decrease by 20ml/kg/day
Day 2	FB of -6 or less	FB of 0 or more
Day 3	FB of -8 or less	FB of -2 or more
Day 4	FB of -8 or less	FB of -3 or more
Day 5	FB of -7 or less	FB of -1 or more
Day 6	FB of -7 or less	FB of 1 or more
Day 7	FB of -4 or less	FB of 5 or more
Day 8	FB of -3 or less	FB of 7 or more
Day 9	FB of 0 or less	FB of 9 or more
Day 10	FB of 1 or less	FB of 10 or more
Day 11	FB of 2 or less	FB of 11 or more
Day 12	FB of 4 or less	FB of 13 or more
Day 13	FB of 5 or less	FB of 15 or more
Day 14	FB of 6 or less	FB of 17 or more

Restrictive fluid group

	Total fluid intake increase by 20 ml/kg/day	Total fluid intake decrease by 20 ml/kg/day
Day 2	FB of -10 or less	FB of -1 or more
Day 3	FB of -13 or less	FB of -3 or more
Day 4	FB of -13 or less	FB of -4 or more
Day 5	FB of -12 or less	FB of -2 or more
Day 6	FB of -11 or less	FB of 0 or more
Day 7	FB of -9 or less	FB of 2 or more
Day 8	FB of -7 or less	FB of 2 or more
Day 9	FB of -5 or less	FB of 4 or more
Day 10	FB of -4 or less	FB of 6 or more
Day 11	FB of -3 or less	FB of 7or more
Day 12	FB of -2 or less	FB of 9 or more
Day 13	FB of 0 or less	FB of 10 or more
Day 14	FB of 0 or less	FB of 12 or more

Parenteral fluid intake will be increased beyond the maximum for each group (150 ml/kg/day in the restricted and 170ml/kg/day in the non-restricted group). In the presence of hypernatremia, sodium levels of 145 to 155 milliequivalent per litre, total fluid intake will be advanced by 10 to 20 ml/kg/day and for sodium levels above 155 milliequivalent per litre, total fluid intake will be advanced by 20 ml/kg/day.

Fluid restriction below 150 ml/kg/day considered in presence of cardiac dysfunction, pulmonary edema and Acute kidney injury (AKI).

Fluid management in the event of shock, oliguria (urine less than 1m/kg/hour) and severe hyponatremia will be according to discretion of treating clinicians.

these instances will be protocol deviations.

Feeding will be started as trophic feeds at 24 to 48 hours and advanced by 20- 25 ml/kg/day in SGA, 25-30 ml/kg/day for AGA infants and will reach the maximum intake of 170 ml/kg/day in RF group and 190ml/kg/day in NF group will be maintained until the completion of 4 weeks of postnatal age.

The feeds will be either MOM, PDHM until 33 weeks of gestation and postnatal weight of 1.5 kgs. Fortification will be started after a feed intake of 100-150ml/kg/day is achieved and preferably between 7-10 days whichever is earlier. Bovine based HMF will be used. TPN will be discontinued if the fluid rate is less than 1 ml/hour.

Primary outcome assessment:

Primary extubation criteria:

1. SPo2 > 92% for more than 80% of the time with Fio2 <35%

2. MAP < 8 cm of water

3. pH more than 7.25 and PaCO2 < 50 on capillary or arterial blood gas

Infants will be extubated to CPAP or NIPPV. If infant is reventilated within 48 h of primary extubation, the duration of primary ventilation will also include the period of reventialtion

Re-ventilation criteria:

1.Fio2 > 40% ( or >60% after first month)

2 pH < 7.20 and PaCO2 >60 on capillary or arterial gas.

3.More than 1 apnoeic episode requiring IPPV in a 24 hour period or more than 3 apnoeic episodes needing tactile stimulation in one hour.

4. An urgent need for reintubation and mechanical ventilation, (shock, seizures or adverse effect from non-invasive ventilation such as pneumothorax or pneumoperitoneum) as determined by the treating neonatologist.

Infants that are hypoxic or acidotic on CPAP will be given a trial of NIPPV.

NIPPV criteria:

Starting at PIP of 16-18 cm of water, PEEP of 6-7 cm of water, inspiratory time of 0.4-0.5 seconds, respiratory rates of 40 per minute and increasing to maximum PIP of 22 -24 cm of water and PEEP of 8cm.

Sample size calculation

We estimated sample size using two sample means test (t test) assuming a common standard deviation in both groups. By restricting fluid intake in first 2 weeks of age with aim to reduce positive fluid balance and maintaining a negative fluid balance, we expect reduction in duration of primary mechanical ventilation by atleast 2 days.

To test this hypothesis for a study power of 80% and two sided significance level of 0.05. A total sample size of 132 (66 in each group) will be required.