Clinical trial NCT06954142: Restricted Versus Liberal Fluid Intake for Prevention of Bronchopulmonary Dysplasia
Official title: Restricted Versus Liberal Fluid Intake for Prevention of Bronchopulmonary Dysplasia - RELIEF Trial. A Cluster-randomised Multiple Period Cross-over Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Bronchopulmonary Dysplasia
Keywords: Fluid Restriction
Preterm Infants
Lead sponsor: University Children's Hospital Basel
Sponsor class: OTHER
Collaborators: name: Swiss Neonatal Network
First posted: 2025-05-01
Enrollment: 750
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Pragmatic, registry-linked, multicentre, open-label, cluster-randomised, multiple period, cross-over, effectiveness trial
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Bronchopulmonary dysplasia (BPD)
timeFrame: From enrolment to 36 weeks postmenstrual age
Secondary outcomes:
measure: Complications of prematurity
timeFrame: From enrolment to 36 weeks postmenstrual age
measure: Days to reach full feeds
timeFrame: From enrolment to 36 weeks postmenstrual age
measure: Need of diuretics
timeFrame: From enrolment to 36 weeks postmenstrual age
measure: Need of corticosteroids
timeFrame: From enrolment to 36 weeks postmenstrual age
measure: Need of respiratory support
timeFrame: At first discharge home, on average 37 weeks postmenstrual age
measure: Growth
timeFrame: at birth and 36 weeks postmenstrual age
measure: Daily caloric intake
timeFrame: From enrolment to 36 weeks postmenstrual age
measure: Dehydration
timeFrame: From enrolment to 36 weeks postmenstrual age
measure: Fluid overload
timeFrame: From enrolment to 36 weeks postmenstrual age
measure: Age at discharge
timeFrame: At first discharge home, on average 37 weeks postmenstrual age
measure: Tube feeding
timeFrame: At first discharge home, on average 37 weeks postmenstrual age
Other outcomes:
measure: Growth
timeFrame: from 36 weeks postmenstrual age, 6-12 and 18-24 months post-term
measure: Respiratory outcome
timeFrame: from 36 weeks postmenstrual age, 6-12 and 18-24 months post-term
measure: Visits to the emergency
timeFrame: From discharge to 6-12 and 18-24 months
measure: Neurodevelopmental outcome
timeFrame: from enrolment to 18-24 months post-term
Locations:
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau AG, Klinik für Kinder u. Jugendliche
city: Basel
country: Switzerland
facility: University Children's Hospital Basel UKBB
city: Bern
country: Switzerland
facility: Inselspital Bern, Kinderklinik
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden, Departement Kinder- und Jugendmedizin
city: Genève
country: Switzerland
facility: Hôpitaux universitaires de Genève (HUG), Unité de Néonatologie
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital, Kinderspital
city: St. Gallen
country: Switzerland
facility: Ostschweizer Kinderspital & Neonatologie und Frauenklinik KSSG, Perinatalzentrum St. Gallen
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich, Klinik für Neonatologie
Study officials:
affiliation: University Children's Hospital Basel, UKBB
name: Sven Schulzke, Prof.MD
role: PRINCIPAL_INVESTIGATOR
References: