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Restricted Versus Liberal Fluid Intake for Prevention of Bronchopulmonary Dysplasia

Restricted Versus Liberal Fluid Intake for Prevention of Bronchopulmonary Dysplasia - RELIEF Trial. A Cluster-randomised Multiple Period Cross-over Trial.

Status
Recruiting
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT06954142
Acronym
RELIEF
Enrollment
750
Registered
2025-05-01
Start date
2025-07-12
Completion date
2029-12-31
Last updated
2025-08-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bronchopulmonary Dysplasia

Keywords

Fluid Restriction, Preterm Infants

Brief summary

The aim of this study is to determine whether restricted fluid intake (135 ±5 mL/kg/day) compared to liberal fluid intake (165 ±5 mL/kg/day) from day 8 of life reduces the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age or prior death in preterm infants born \<30 weeks gestational age.

Detailed description

Complications of preterm birth remain the leading cause of death in children under five years of age worldwide, accounting for approximately one million deaths annually. Among the survivors, bronchopulmonary dysplasia (BPD) is the most common severe complication. BPD is a chronic lung disease characterized by prolonged need for respiratory support and oxygen therapy, poor postnatal growth, and long-term impairments in lung function and neurodevelopment. Despite advancements in neonatal care, BPD is the most common chronic lung disease in infancy and associated with increased mortality, repeated hospitalisation throughout childhood, impaired lung function up into adulthood, and long-term neurodevelopmental impairment. The incidence of BPD has remained stable over the past 15 years. This is likely due to the improved survival of extremely preterm infants, who are at the highest risk for BPD. A key feature of evolving BPD is the accumulation of interstitial pulmonary edema, which reduces lung compliance and increases the need for respiratory support, thereby perpetuating a cycle of lung damage. Currently, diuretics are sometimes used to manage pulmonary edema in preterm infants. While they can improve lung function in the short term, they come with potential risks including bone demineralization, nephrotoxicity, electrolyte imbalances, and impaired growth. As a potentially safer alternative, fluid restriction is sometimes used to prevent or manage pulmonary edema. It is hypothesized to improve lung mechanics and reduce the need for respiratory support, without the adverse effects associated with medications. However, there is no robust evidence on optimal fluid targets in these patients. SwissNeoNet, consisting of all nine Swiss NICUs, is a mandatory national registry, where data on all infants born before 32 weeks of gestation and/or with a birth weight \< 1501 g are collected. Fluid management practices vary among Swiss neonatal intensive care units (NICUs) following international guidelines recommending 135 to 180 mL/kg/day of fluids. This variation may contribute to the differing rates of BPD and mortality observed across centers, but fluid intake is not routinely captured in SwissNeoNet data, making it difficult to assess its impact. In summary, although fluid restriction shows potential as a simple and low-risk intervention to reduce the incidence of BPD, current evidence is insufficient to support its routine use. There is a clear need for a robust, contemporary, and pragmatic trial to evaluate whether fluid restriction, started after the first week of life, can safely and effectively reduce the incidence of BPD or death in very preterm infants.

Interventions

Fluid restriction strategy (fluid target 135 ±5 mL/kg/d)

OTHERLiberal fluid intake

Liberal fluid intake strategy (fluid target 165 ± 5 mL/kg/d)

Sponsors

Swiss Neonatal Network
CollaboratorNETWORK
University Children's Hospital Basel
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE

Intervention model description

Pragmatic, registry-linked, multicentre, open-label, cluster-randomised, multiple period, cross-over, effectiveness trial

Eligibility

Sex/Gender
ALL
Age
8 Days to No maximum
Healthy volunteers
No

Inclusion criteria

* Hospitalised preterm infants born before 30 weeks 0 days gestation * Signed informed consent for further research use of health-related data

Exclusion criteria

* congenital malformations * diseases likely to affect life expectancy, lung function, fluid strategy, or neurodevelopment * renal disease requiring fluid management outside the clinical standard of care * congenital heart disease not including patent ductus arteriosus (PDA)

Design outcomes

Primary

MeasureTime frameDescription
Bronchopulmonary dysplasia (BPD)From enrolment to 36 weeks postmenstrual ageProportion of infants with BPD measured at 36 weeks postmenstrual age or prior death.

Secondary

MeasureTime frameDescription
Need of respiratory supportAt first discharge home, on average 37 weeks postmenstrual ageDuration of mechanical ventilation, non-invasive respiratory support, total positive pressure support, supplemental oxygen support, supplemental home oxygen, home ventilation
DehydrationFrom enrolment to 36 weeks postmenstrual ageDehydration (sodium level ≥ 150 mmol/L plus clinical signs of dehydration)
Fluid overloadFrom enrolment to 36 weeks postmenstrual ageFluid overload (sodium level ≤ 130 mmol/L plus clinical signs of fluid overload)
Age at dischargeAt first discharge home, on average 37 weeks postmenstrual agePostmenstrual age at discharge home
Tube feedingAt first discharge home, on average 37 weeks postmenstrual ageTube feeding at discharge home
Complications of prematurityFrom enrolment to 36 weeks postmenstrual ageMajor complications of prematurity including necrotising enterocolitis ≥ Bell's stage 2, retinopathy of prematurity requiring treatment, patent ductus arteriosus requiring treatment, abnormal brain ultrasound, late onset sepsis
Days to reach full feedsFrom enrolment to 36 weeks postmenstrual ageDays to reach full feeds defined as 150 ml/kg/d or being off parenteral nutrition
Need of diureticsFrom enrolment to 36 weeks postmenstrual ageTreatment with diuretics (days on diuretics)
Need of corticosteroidsFrom enrolment to 36 weeks postmenstrual ageSystemic postnatal corticosteroids for prevention or treatment of bronchopulmonary dysplasia
Growthat birth and 36 weeks postmenstrual agedifference in weight, length, and head circumference z-score at 36 weeks postmenstrual age and at birth, respectively
Daily caloric intakeFrom enrolment to 36 weeks postmenstrual ageDaily caloric intake from day 8 of life to 36 weeks postmenstrual age

Other

MeasureTime frameDescription
Visits to the emergencyFrom discharge to 6-12 and 18-24 monthsVisits to the emergency department from discharge to 6-12 months for any reason
Neurodevelopmental outcomefrom enrolment to 18-24 months post-termNeurodevelopmental outcome as per PARCA-R questionnaire
Growthfrom 36 weeks postmenstrual age, 6-12 and 18-24 months post-termGrowth (weight, length, and head circumference z-score)
Respiratory outcomefrom 36 weeks postmenstrual age, 6-12 and 18-24 months post-termRespiratory outcome as per Basel-Bern-Infant-Lung-Development cohort study questionnaire

Countries

Switzerland

Contacts

Primary ContactAnne Carrer
anne.carrer@ukbb.ch+4161 704 2853
Backup ContactMichel Schrutt
relief@ukbb.ch

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026