Fluid Restriction Keeps Children Dry (LESSER)

Fluids in Mechanically Ventilated Children With Acute Infectious Lung Disease: How Dry Should They be?

Rationale: Fluid overload is a common complication in children who are admitted to the pediatric intensive care for mechanical ventilation. Acute lung infection is a frequent cause for admission to the PICU and forms an uniform group with a single organ failure. In these critically ill children, fluid overload is associated with adverse outcome. Restricting the volume of fluids already in an early stage of ICU admission may prevent fluid overload during mechanical ventilation and thus improve clinical outcome. However, at the same time fluid restriction may interfere with appropriate energy and macronutrient intake that is needed for recovery.

Objective: The main goal of this pilot study is to evaluate the feasibility of a restrictive fluid management protocol and investigate its effect on the occurrence of fluid overload in mechanically ventilated children with acute infectious lung disease.

Study design: Single-center prospective randomized feasibility and pilot study in preparation of a multi-center randomized controlled trial (RCT).

Study population: Mechanically ventilated children with (suspicion of) acute infectious lung disease admitted to the pediatric intensive care unit (PICU) of the Emma Children's Hospital, Academic Medical Center, Amsterdam.

Intervention: Patients receive either liberal (control group) or a restrictive (experimental group) fluid treatment, while ensuring appropriate caloric intake.

Main study parameters/endpoints: Primary outcomes are cumulative fluid balance and body weight during the first week of mechanical ventilation. Secondary outcomes (in preparation of the larger multi-center RCT) include: mortality, duration of mechanical ventilation and oxygenation indices. To determine the feasibility, in- and exclusion rate, adherence to treatment arms, need for fluid bolus, need for diuretics and hemodynamic indices as well as energy and protein intake are studied.

Both fluid management protocols reflect a variant of current clinical practice, hence will not provide extra burden or risk to patients included in the study. Patients will be randomized to either of the fluid protocol arms on admission to the PICU (at start of mechanical ventilation). Patients included in the restrictive fluid treatment arm might have direct benefit from the study if indeed fluid overload is less common in this group.

Study Overview

• Status: Unknown
• Conditions: Critical Illness; Respiratory Insufficiency; Fluid Overload; Respiratory Infection
• Intervention / Treatment: Other: Restrictive fluid regimen; Other: Liberal fluid regimen

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Academic Medical Center
    • Contact: Sarah A Ingelse, MD; Phone Number: 0031-20-5665675; Email: s.a.ingelse@amc.nl
    • Contact: Job BM van Woensel, Professor; Phone Number: 0031-20-566579; Email: ic.kinderen@amc.nl
    • Sub-Investigator: Sarah A Ingelse, MD
    • Sub-Investigator: Reinout A Bem, MD PhD
    • Principal Investigator: Job BM van Woensel, Professor (MD PhD)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 10 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent by parents or legal caretakers
• Admitted to the PICU of the Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
• Intubated and mechanically ventilated, with an anticipated duration of mechanical ventilation of at least 72 hours at enrolment (as judged by investigator or pediatrician on duty)
• Patients with an acute infectious lung disease, including (suspected) viral, bacterial or fungal infection

Exclusion Criteria:

• Patients in need of a particular fluid regimen (either restrictive or liberal) due to their medical history (e.g. cardiovascular disease and/or congenital (cyanotic) heart disease)
• Use of previous and/or maintenance diuretic treatment
• Ongoing (fluid) resuscitation on admission
• Acute kidney injury with need for renal replacement therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Restrictive fluid treatment; Restrictive fluid regimen	Other: Restrictive fluid regimen; In this treatment arm, patients will receive a maximal daily fluid intake of 70% of normal requirements (for a healthy child).
ACTIVE_COMPARATOR: Liberal fluid treatment; This is seen as current standard clinical treatment, wherein patients will receive a more liberal fluid regimen.	Other: Liberal fluid regimen; This is considered current standard clinical treatment, wherein patients will receive a fluid regimen of >85% of normal fluid recommendations (for a healthy child).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative fluid balance	First week of mechanical ventilation
Body weight	First week of mechanical ventilation

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of mechanical ventilation	Through study completion, an average of 1 week
Oxygenation indices	Through study completion, an average of 1 week
Mortality	Up to 90 days after admission

Other Outcome Measures

Outcome Measure	Time Frame
In- and exclusion rate	Through study completion, an average of 1 week
Adherence to treatment arms	Through study completion, an average of 1 week
Need for fluid bolus	Through study completion, an average of 1 week
Need for diuretics	Through study completion, an average of 1 week
Need for vasopressors or inotropic drugs	Through study completion, an average of 1 week
Energy and protein intake	Through study completion, an average of 1 week
Gastrointestinal complaints	Through study completion, an average of 1 week
Hemodynamic indices	Through study completion, an average of 1 week
Occurrence of electrolyte imbalances	Through study completion, an average of 1 week

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Ingelse SA, Geukers VG, Dijsselhof ME, Lemson J, Bem RA, van Woensel JB. Less Is More?-A Feasibility Study of Fluid Strategy in Critically Ill Children With Acute Respiratory Tract Infection. Front Pediatr. 2019 Dec 10;7:496. doi: 10.3389/fped.2019.00496. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (ANTICIPATED): September 1, 2018
• Study Completion (ANTICIPATED): November 1, 2018

Study Registration Dates

• First Submitted: December 5, 2016
• First Submitted That Met QC Criteria: December 7, 2016
• First Posted (ESTIMATE): December 12, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): December 12, 2016
• Last Update Submitted That Met QC Criteria: December 7, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Respiration Disorders; Disease Attributes; Respiratory Insufficiency; Critical Illness; Respiratory Tract Infections
• Other Study ID Numbers: 2016_096