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NCT Number: NCT07494643

Fluid-responsiveness in Children Ventilated With LOW Tidal Volume - The FLOW Study.

In this study of diagnostic accuracy, the investigators aim to validate a fluid-responsiveness test in critically ill children mechanically ventilated with low tidal volume. This test is the famous respiratory variability of peak aortic velocity (ΔVPeak), which is based on cardiopulmonary interactions but is only validated in mechanically ventilated children with a tidal volume of at least 8ml/kg, which is uncommon nowadays. This would help physicians to identify children ventilated with low tidal volume and suffering from acute circulatory failure that could benefit from a volume expansion, thus avoiding a potentially useless or even dangerous fluid expansion that could lead to fluid overload.

To this end, the diagnostic accuracy of ΔVPeak to predict fluid responsiveness (define as a 15% increase in echocardiographically measured SV after volume expansion) will be measured in mechanically ventilated children with low tidal volume and requiring fluid bolus.

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Key information

Conditions

Circulatory Failure (Shock) Pathologic Processes Pathological Conditions, Signs and Symptoms Shock

Age range

0 day–15 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU d'Amiens Picardie, Amiens, France

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About this study

Volume expansion is the cornerstone of acute circulatory failure treatment in children. However, inappropriate administration can lead to fluid overload, which is associated with poor outcome. Thus, the search for indicators to predict fluid responsiveness is a major issue in pediatric intensive care unit. In such an emergency context, this assessment must be as simple and fast as possible, and ideally non-invasive. In children, ΔVPeak is the most used and studied test and has an excellent diagnostic accuracy. Moreover, this echocardiography-based test is noninvasive and easy to perform. Unfortunately, this test is only validated in children ventilated with tidal volume of at least 8ml/kg, a rare situation in practice. However, some recent data in both adults and preterm neonates suggest that fluid responsiveness tests based on cardiopulmonary interactions could be used even in patients on protective ventilation. Yet, to date, the diagnostic accuracy of ΔVPeak has never been investigated in children on protective ventilation (low tidal volume), although it is now the most common ventilation strategy in pediatric intensive care units. Therefore, the investigators hypothesize that ΔVPeak is reliable to predict fluid responsiveness in children mechanically ventilated with 6ml/kg tidal volume.

Therefore, the investigatorswill evaluate the diagnostic accuracy of ΔVPeak in critically ill children mechanically ventilated with low tidal volume, and for whom the physician in charge prescribed a 10ml/kg volume expansion to treat circulatory failure. The index test will be ΔVPeak. Fluid responsiveness will be defined as a > 15% increase in echocardiographically-measured stroke volume between baseline and within one hour after fluid expansion (gold standard test).

In this non-interventional multicentric prospective study of diagnostic accuracy, children requiring a 10ml/kg volume expansion will be included. Volume expansion will be delayed for a few minutes (<3min) in order to complete the baseline echocardiogram with standardized measurements, but no supplemental blood test or invasive parameters will be collected. Another echocardiographic evaluation will be conducted within one hour after volume expansion. Patients will be follow-up until PICU discharge.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Age between 0 days and 15 years old
  • Patient hospitalized in a pediatric intensive care unit.
  • Prescription of a 10ml/kg (±20%) fluid expansion by the physician in charge, as a standard care treatment of circulatory failure (precise indication is up to the physician in charge).
  • Mechanical ventilation
  • Tidal volume < 6ml/kg (±15%)
  • Fluid responsiveness echocardiographic assessment as of routine care

Exclusion criteria

  • Prematurity (corrected gestational age bellow 37 weeks)
  • Arythmia
  • Hemodynamic instability making dangerous the delay necessary for any measurement.
  • Prone position
  • Impairment of echocardiographic acoustic window
  • Extracorporeal membrane oxygenation
  • Respiratory rate (measured) > 60 cycles per minute (including high frequency oscillation)
  • Significant breathing movements (high work of breathing, clinically assessed)
  • Restlessness with desynchronization patient/ventilator
  • Open chest
  • Cardiogenic pulmonary oedema
  • Known intracardiac or vascular shunt
  • Known hemodynamically significant valvopathy
  • Opposition to participate expressed by the patient or by a parent or legal guardian

Treatment and study plan

Echocardiographic

Procedure

Patients included in this study would have received volume expansion anyway, as the prescription of 10ml/kg volume expansion by the physician in charge is the main inclusion criterion. The purpose of this study is to evaluate the diagnostic accuracy of a fluid responsiveness test. To this end, patients will undergo echocardiographic assessments, which are non-invasive, non-radiative, well tolerated and commonly used in this population as a standard of care in our center. No additional blood test or invasive parameters will be collected be collected.

Primary outcomes

  1. Area under the ROC curve (AUROC, percent) of ΔVPeak to diagnose fluid responsiveness

    Time frame: Baseline

    The primary outcome measure of a diagnostic accuracy study is the discriminative ability of an index test (expressed as an area under the ROC curve) to diagnose a condition (defined by a positive gold-standard reference test). In this study:

    • The index test is ΔVPeak at baseline = difference between maximal and minimal peak aortic velocity (m/s) during 5 cardiac cycles, divided by mean peak aortic velocity (m/s). Peak aortic velocity is measured by transthoracic echocardiography with pulsed-Doppler in the left ventricular outflow tract from an apical 5-chambers view.
    • The condition is "fluid responsiveness"
    • The gold-standard reference test to diagnose fluid responsiveness is a stroke volume (SV) increase of at least 15% between baseline and after volume expansion: ΔSV-VE > 15% = ((SV after volume expansion - SV at baseline) / SV at baseline) > 15%. SV (ml) will be measured by transthoracic echocardiography as the product of left ventricular outflow tract surface (cm², from a par

Secondary outcomes

  1. AUROC (percent) of the following index test to diagnose fluid responsiveness

    Time frame: Baseline

    Respiratory variability of peak pulmonary velocity i.e. difference between maximal and minimal peak pulmonary velocity (m/s) during 6 cardiac cycles, divided by mean pulmonary aortic velocity (m/s). Peak pulmonary velocity is measured by transthoracic echocardiography with pulsed-Doppler in the right ventricular outflow tract from parasternal view.

  2. Influencing factors

    Time frame: Baseline

    AUROC of deltaVPeak to diagnose fluid responsiveness in the following subgroups:

    • Age below 2 years
    • Age between 2 and 5 years
    • Age between 5 and 15 years
    • Anormal right ventricle (defined as a right ventricle dilatation (i.e., basal right ventricle diameter superior to the basal left ventricle diameter) or dysfunction (i.e., a tricuspid annular plane systolic excursion value or as a S wave tissular doppler value at lateral tricuspid annulus below 2 standard deviations for age and body surface area))
    • Spontaneous breathing (clinically defined)
    • Altered pulmonary compliance (defined as a pulmonary compliance of less than 0.5ml/kg/cmH2O, measured with the ventilator)
    • Pediatric cute respiratory distress syndrome (clinically defined as per international guidelines)

    And comparison of thoses AUROC (using a De Long test)

  3. Poor respiratory tolerance

    Time frame: Baseline , immediately after volume expansion

    Association between the binary outcome "poor respiratory tolerance of volume expansion" (composite outcome defined as the presence of at least one of the following conditions at the Time Frame "Hours 4": clinically meaningful oxygenation worsening compared to baseline, measured with oxygen saturation related to oxygen intake (fraction of inspired oxygen, percent); clinically meaningful pulmonary compliance worsening compared to baseline, measured in ml/cmH2O with the ventilator; therapeutic incrementation for acute respiratory distress syndrome such as neuromuscular blockade, prone positioning, inhaled nitric oxid or extracorporeal membrane oxygenation) and the following baseline echocardiographic parameters:

    • Right ventricle dilatation (binary variable, defined as basal right ventricle diameter superior to basal left ventricle diameter)
    • Right ventricle systolic dysfunction (binary variable, defined as a tricuspid annular plane systolic excursion value or as a S wave tissul

  4. Proportion of patients in each age category, according to fluid responsiveness

    Time frame: Baseline

    • Categorical variable (age category: 0-2 years / 2-5 years / 5-15 years)
    • Unit : percent of patients

  5. Sex, in patients with and without fluid responsiveness

    Time frame: Baseline

    • Binary variable (M/F)
    • Unit: percent of patients

  6. Weight, in patients with and without fluid responsiveness

    Time frame: Baseline

    • Continuous variable
    • Unit: kg

  7. Volume of fluid expansion in patients with and without fluid responsiveness

    Time frame: Baseline

    Volume of fluid expansion during the last 24 hours before inclusion

    • Continuous variable
    • Unit: ml

  8. Heart rate in patients with and without fluid responsiveness

    Time frame: Baseline

    • continuous variable
    • Unit: bpm

  9. Arterial pressure in patients with and without fluid responsiveness

    Time frame: Baseline

    • continuous variable
    • Unit: mmHg

  10. Urine in patients with and without fluid responsiveness

    Time frame: Baseline,

    Urine output

    • continuous variable
    • Unit: ml/kg/h

  11. Capillary refill time with and without fluid responsiveness

    Time frame: Baseline

    • continuous variable
    • Unit: sec

  12. Mottling, in patients with and without fluid responsiveness

    Time frame: Baseline

    • Binary variable (yes/no)
    • Unit: percent of patients

  13. fluid balance in patients with and without fluid responsiveness

    Time frame: Baseline

    Cumulative fluid balance since intensive care admission

    • continuous variable
    • Unit : ml

  14. PELODS2 score in patients with and without fluid responsiveness

    Time frame: Baseline

    • continuous variable
    • Unit : n

  15. Inotropic Score in patients with and without fluid responsiveness

    Time frame: Baseline

    • continuous variable
    • Unit : n

  16. Left ventricular ejection fraction in patients with and without fluid responsiveness

    Time frame: Baseline

    • continuous variable
    • Unit : percentage

  17. venous pressure in patients with and without fluid responsiveness

    Time frame: Baseline

    • continuous variable
    • Unit : mmHg

  18. Blood lactate in patients with and without fluid responsiveness

    Time frame: Baseline

    • continuous variable
    • Unit : mmol/L

  19. Length of mechanical ventilation in patients with and without fluid responsiveness

    Time frame: Day 28

    • Continuous variable.
    • Unit: days.

  20. length of stay in intensive care in patients with and without fluid responsiveness

    Time frame: Day 28

    • continuous variable
    • Unit : days.

  21. Mortality in patients with and without fluid responsiveness

    Time frame: Day 28

    • Mortality: binary variable (yes/no)
    • Unit: percent of patients

Study contacts

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

Julien GOTCHAC, MD

CONTACT

[email protected]

0556795913 ext. +33

Sponsors and collaborators

Lead sponsor

University Hospital, Bordeaux

Other

Registry information

Acronym: FLOW

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Mar 27, 2026
Registry last updated
Apr 7, 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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