Intravenous Fluids in Hospitalised Children

Fluid Therapy in Acutely Ill Children - a Randomized Controlled Trial

The main objective of the trial is to evaluate the risk of hypokalemia following administration of a isotonic solution compared to a hypotonic solution in acutely ill hospitalised children, who need intravenous fluid therapy.

Study Overview

• Status: Completed
• Conditions: Hyponatremia; Dehydration; Hypokalemia; Hypernatremia
• Intervention / Treatment: Drug: Plasmalyte Glucos 50 mg/mL; Drug: 0.45% saline in 5% dextrose

Detailed Description

The main objective of the trial is to evaluate the risk of hypokalemia (low plasma potassium concentration) following administration of a Plasmalyte Glucos 50 mg/mL solution compared to a 0.45% saline in 5% dextrose solution in acutely ill hospitalised children, who need intravenous fluid therapy. The secondary objective of the trial is to evaluate the risk of hyponatremia (low plasma sodium concentration) and the risk of hypernatremia (high plasma sodium concentration) following administration of isotonic solution compared to hypotonic solution.

• Study Type: Interventional
• Enrollment (Actual): 660
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Oulu, Finland, 90029
    • Oulu University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acutely ill hospitalised children
• Need for intravenous fluid therapy

Exclusion Criteria:

• An initial plasma sodium concentration of lower than 130 mmol/L
• An initial plasma sodium concentration of higher than 150 mmol/L
• An initial plasma potassium concentration of lower than 3.0 mmol/L
• Need for 10% glucose solution
• Diabetes
• Diabetes insipidus
• Diabetic ketoacidosis
• Renal disease that needs dialysis
• Protocol-determined chemotherapy hydration
• Severe liver disease
• Inborn errors of metabolism that need protocol-determined fluid therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isotonic solution; Plasmalyte Glucos 50 mg/mL; total daily fluid requirements are estimated using the Holiday-Segar method plus possible dehydration (according to child's weight loss during acute illness); intravenous fluids are administered using delivery pumps programmed for an hourly infusion rate (mL/hour); intravenous fluids are administered as long as needed during hospitalization, but no longer than seven days after admission.	Drug: Plasmalyte Glucos 50 mg/mL; Solution contains potassium chloride 5 mmol/L and sodium chloride 140 mmol/L.; Other Names: ATC-code: B05BB02
Active Comparator: Hypotonic solution; 0.45% saline in 5% dextrose; total daily fluid requirements are estimated using the Holiday-Segar method plus possible dehydration (according to child's weight loss during acute illness); intravenous fluids are administered using delivery pumps programmed for an hourly infusion rate (mL/hour); intravenous fluids are administered as long as needed during hospitalization, but no longer than seven days after admission.	Drug: 0.45% saline in 5% dextrose; Solution contains potassium chloride 20 mmol/L and sodium chloride 80 mmol/L.; Other Names: 0.45% NaCl in 5% dextrose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of children with a clinically significant electrolyte disorder	Plasma potassium concentration<3.5 mmol/L, or hypernatremia >148 mmol/L, or hyponatremia <132 mmol/L	Plasma sodium and potassium concentrations are assessed daily (at 7 am) during the intravenous fluid therapy from randomization up to seven days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of children with hyponatremia	Plasma sodium concentration of lower than 132 mmol/L.	Plasma sodium and potassium concentrations are assessed daily (at 7 am) during the intravenous fluid therapy from randomization up to seven days.
Proportion of children with hypernatremia	Plasma sodium concentration of higher than 148 mmol/L.	Plasma sodium and potassium concentrations are assessed daily (at 7 am) during the intravenous fluid therapy from randomization up to seven days.
Proportion of children with hypokalemia	Potassium < 3.5 mmol/L	0-7 days from study entry
Proportion of children with severe hypokalemia	Hypokalemia defined as concentration of potassium <3.0 mmol/L	0-7 days from study entry
Fluid retention (g) measured by the weight change	Weight (g) at discharge - weight (g) at admission	0-7 days: Body weight is measured daily (at 7 am) during the intravenous fluid therapy from randomization up to seven days.
Concentration of copeptin in plasma samples	Copeptin plasma concentration	6-24 hours after study entry
Concentration of bicarbonate (HCO3) in plasma samples	Plasma concentration of bicarbonate HCO3	1-3 days after study entry
Acidosis measured by pH in blood gas analysis	pH in the blood gas analysis	1-3 days after study entry
Alkalosis measured by base excess (BE) in blood gas analysis	Base excess in the blood gas analysis	1-3 days after study entry
Duration of intravenous fluid therapy	Hours from study entry to the stop of fluid therapy	From randomization up to seven days.
Proportion of children who needed change of the study fluid treatment	Any change of the fluid used in the treatment	From randomization up to seven days.
Proportion of children admitted to ICU	Admission to ICU for any reason	From randomization up to seven days.
Time to discharge from hospital in hours	Time from study entry to discharge in hours	From randomization up to seven days.
Number of deaths	Any death during the study	0-30 days from study entry

Collaborators and Investigators

• Sponsor: University of Oulu
• Collaborators: Oulu University Hospital
• Investigators: Principal Investigator: Terhi Tapiainen, MD, Oulu University Hospital

Publications and helpful links

General Publications

• Lehtiranta S, Honkila M, Kallio M, Paalanne N, Peltoniemi O, Pokka T, Renko M, Tapiainen T. Risk of Electrolyte Disorders in Acutely Ill Children Receiving Commercially Available Plasmalike Isotonic Fluids: A Randomized Clinical Trial. JAMA Pediatr. 2021 Jan 1;175(1):28-35. doi: 10.1001/jamapediatrics.2020.3383. Erratum In: JAMA Pediatr. 2021 Feb 1;175(2):212.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2016
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): April 15, 2019

Study Registration Dates

• First Submitted: October 4, 2016
• First Submitted That Met QC Criteria: October 5, 2016
• First Posted (Estimate): October 6, 2016

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 20, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Isotonic; Hypotonic; Intravenous fluids
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Water-Electrolyte Imbalance; Hyponatremia; Dehydration; Hypernatremia; Hypokalemia; Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: EETTMK 48/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No