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NCT Number: NCT06954142

Restricted Versus Liberal Fluid Intake for Prevention of Bronchopulmonary Dysplasia

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.

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Key information

Age range

8 day and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Kantonsspital Aarau AG, Klinik für Kinder u. Jugendliche, Aarau, Switzerland

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

fluid restriction

Other

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

Liberal fluid intake

Other

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

Primary outcomes

  1. Bronchopulmonary dysplasia (BPD)

    Time frame: From enrolment to 36 weeks postmenstrual age

    Proportion of infants with BPD measured at 36 weeks postmenstrual age or prior death.

Secondary outcomes

  1. Complications of prematurity

    Time frame: From enrolment to 36 weeks postmenstrual age

    Major 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

  2. Days to reach full feeds

    Time frame: From enrolment to 36 weeks postmenstrual age

    Days to reach full feeds defined as 150 ml/kg/d or being off parenteral nutrition

  3. Need of diuretics

    Time frame: From enrolment to 36 weeks postmenstrual age

    Treatment with diuretics (days on diuretics)

  4. Need of corticosteroids

    Time frame: From enrolment to 36 weeks postmenstrual age

    Systemic postnatal corticosteroids for prevention or treatment of bronchopulmonary dysplasia

  5. Need of respiratory support

    Time frame: At first discharge home, on average 37 weeks postmenstrual age

    Duration of mechanical ventilation, non-invasive respiratory support, total positive pressure support, supplemental oxygen support, supplemental home oxygen, home ventilation

  6. Growth

    Time frame: at birth and 36 weeks postmenstrual age

    difference in weight, length, and head circumference z-score at 36 weeks postmenstrual age and at birth, respectively

  7. Daily caloric intake

    Time frame: From enrolment to 36 weeks postmenstrual age

    Daily caloric intake from day 8 of life to 36 weeks postmenstrual age

  8. Dehydration

    Time frame: From enrolment to 36 weeks postmenstrual age

    Dehydration (sodium level ≥ 150 mmol/L plus clinical signs of dehydration)

  9. Fluid overload

    Time frame: From enrolment to 36 weeks postmenstrual age

    Fluid overload (sodium level ≤ 130 mmol/L plus clinical signs of fluid overload)

  10. Age at discharge

    Time frame: At first discharge home, on average 37 weeks postmenstrual age

    Postmenstrual age at discharge home

  11. Tube feeding

    Time frame: At first discharge home, on average 37 weeks postmenstrual age

    Tube feeding at discharge home

Other outcomes

  1. Growth

    Time frame: from 36 weeks postmenstrual age, 6-12 and 18-24 months post-term

    Growth (weight, length, and head circumference z-score)

  2. Respiratory outcome

    Time frame: from 36 weeks postmenstrual age, 6-12 and 18-24 months post-term

    Respiratory outcome as per Basel-Bern-Infant-Lung-Development cohort study questionnaire

  3. Visits to the emergency

    Time frame: From discharge to 6-12 and 18-24 months

    Visits to the emergency department from discharge to 6-12 months for any reason

  4. Neurodevelopmental outcome

    Time frame: from enrolment to 18-24 months post-term

    Neurodevelopmental outcome as per PARCA-R questionnaire

Study contacts

Contact information is provided by the study sponsor or research team.

Anne Carrer

CONTACT

[email protected]

+4161 704 2853

Michel Schrutt

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

University Children's Hospital Basel

Other

Collaborators

  • Swiss Neonatal Network
  • SwissPedNet

Registry information

Official study title

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

Acronym: RELIEF

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
May 1, 2025
Registry last updated
May 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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