Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis
NCT ID: NCT04102371
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
8800 participants
INTERVENTIONAL
2020-08-25
2026-08-31
Brief Summary
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Detailed Description
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Crystalloid fluids can be categorized as non-buffered (most commonly 0.9% normal saline \[NS\]) or buffered/balanced fluids (BF). In the US, the most common BF is lactated Ringer's (LR), but other example include PlasmaLyte. NS and BF are inexpensive, stable at room temperature, and nearly universally available with identical storage volumes and dosing strategies. Notably, both are also of proven clinical benefit in septic shock and have extensive clinical experience for use in fluid resuscitation of critically ill patients. However, despite data suggesting that BF resuscitation may have superior efficacy and safety, NS remains the most commonly used fluid largely based on historical precedent.
To definitively test the comparative effectiveness of NS and BF, a well-powered randomized controlled trial (RCT) is necessary. A large pragmatic randomized trial embedded within everyday clinical practice provides a cost-efficient and generalizable approach to inform clinicians about best comparative effectiveness of common therapies. Data from a prior single-center feasibility study demonstrated that a pragmatic randomized clinical trial of NS versus BF for children with septic shock presenting to an emergency department is feasible and can be successfully carried out by embedding simple study procedures within routine clinical practice. This multi-center study that will now test for differential clinical effects, as part of a definitive comparative effectiveness trial, of NS versus BF for crystalloid resuscitation of pediatric septic shock.
This multicenter phase trial will include enrollment and study procedures across 30+ US and international sites to compare the effectiveness and relative safety of NS versus BF (LR and PlasmaLyte) for crystalloid resuscitation of children with septic shock. The primary endpoint is major adverse kidney events within 30 days along with other secondary clinical, safety, and kidney biomarker endpoints.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Balanced fluids (BF)
Balanced fluids (BF), including Lactated Ringer's and Plasma-Lyte (PL), will be administered to patients randomized to the experimental arm. BF will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calendar day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer
LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
Plasma-lyte
PL is a sterile, nonpyrogenic isotonic solution in a single dose container for intravenous administration. Each 100 mL contains 526 mg of Sodium Chloride, USP (NaCl); 502 mg of Sodium Gluconate (C6H11NaO7); 368 mg of Sodium Acetate Trihydrate, USP (C2H3NaO2•3H2O); 37 mg of Potassium Chloride, USP (KCl); and 30 mg of Magnesium Chloride, USP (MgCl2•6H2O). It contains no antimicrobial agents. The pH is adjusted with sodium hydroxide. The pH is 7.4 (6.5 to 8.0).
0.9% "Normal" Saline Fluid (NS)
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calendar day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal Saline
Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
Interventions
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Lactated Ringer
LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
Normal Saline
Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
Plasma-lyte
PL is a sterile, nonpyrogenic isotonic solution in a single dose container for intravenous administration. Each 100 mL contains 526 mg of Sodium Chloride, USP (NaCl); 502 mg of Sodium Gluconate (C6H11NaO7); 368 mg of Sodium Acetate Trihydrate, USP (C2H3NaO2•3H2O); 37 mg of Potassium Chloride, USP (KCl); and 30 mg of Magnesium Chloride, USP (MgCl2•6H2O). It contains no antimicrobial agents. The pH is adjusted with sodium hydroxide. The pH is 7.4 (6.5 to 8.0).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Clinician concern for septic shock, operationalized as:
1. a "positive" ED sepsis alert confirmed by a physician OR
2. physician decision to treat for septic shock OR
3. a physician diagnosis of septic shock requiring parenteral antibiotics and fluid resuscitation
3. Administration of at least one IV/Intraosseous (IO) fluid bolus for resuscitation and additional fluid deemed likely to be necessary to treat poor perfusion, or clinician judgment that \>1 fluid bolus is highly likely to be required. Poor perfusion is defined as physician's judgement of hypotension or abnormal (either "flash" or "prolonged") capillary refill.
4. Receipt of ≤40 mL/kg IV/IO total crystalloid fluid prior to randomization
5. Parental/guardian permission (informed consent) if time permits; otherwise, Exception from informed consent (EFIC) criteria met
Exclusion Criteria
1. Clinical suspicion for impending brain herniation
2. Known hyperkalemia, defined as non-hemolyzed whole blood or plasma/serum potassium \> 6 mEq/L, based on data available at or before patient meets criteria for study enrollment
3. Known hypercalcemia, defined as plasma/serum total calcium \>12 mg/dL or whole blood ionized calcium \>1.35 mmol/L, based on data available at or before patient meets criteria for study enrollment
4. Known acute fulminant hepatic failure, defined as plasma/serum alanine aminotransferase (ALT) \>10,000 U/L or total bilirubin \>12.0 mg/dL, based on data available at or before patient meets criteria for study enrollment
5. Known history of severe hepatic impairment, defined as cirrhosis, "liver failure", or awaiting transplant
6. Known history of severe renal impairment, defined as peritoneal dialysis or hemodialysis
7. Known metabolic/mitochondrial disorder, inborn error of metabolism, or primary mineralocorticoid deficiency as reported by participant, legally authorized representative (LAR) or accompanying caregiver, or as listed in the medical record
8. Other concern for which the treating clinician deems it unsafe to administer either NS or LR
2. Known pregnancy determined by routine history disclosed by patient and/or accompanying acquaintance.
3. Known prisoner
4. Known allergy to a crystalloid fluid
5. Indication of declined consent to participate based on presence of an opt-out bracelet with appropriate messaging embossed into the bracelet, the presence of the patient's name on an opt-out list that will be kept up-to-date and checked prior to randomization, or verbal "opt-out" prior to enrollment.
2 Months
17 Years
ALL
No
Sponsors
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Boston Children's Hospital
OTHER
Children's Healthcare of Atlanta
OTHER
Children's Hospital Colorado
OTHER
Children's Hospital Los Angeles
OTHER
University of Pittsburgh
OTHER
Morgan Stanley Children's Hospital
OTHER
Children's Hospital and Health System Foundation, Wisconsin
OTHER
Children's Medical Center Dallas
OTHER
St. Louis Children's Hospital
OTHER
Baylor College of Medicine
OTHER
University of California, Davis
OTHER
Children's National Research Institute
OTHER
Children's Hospital Medical Center, Cincinnati
OTHER
Hasbro Children's Hospital
OTHER
Ann & Robert H Lurie Children's Hospital of Chicago
OTHER
Nationwide Children's Hospital
OTHER
Primary Children's Hospital
OTHER
Seattle Children's Hospital
OTHER
University of California, San Francisco
OTHER
University of Michigan
OTHER
Kidz First Hospital Middlemore
UNKNOWN
Gold Coast Hospital and Health Service
OTHER_GOV
Queensland Children's Hospital
OTHER_GOV
Westmead Children's Hospital
UNKNOWN
Sydney Children's Hospitals Network
OTHER
Perth Children's Hospital
UNKNOWN
Starship Children's Hospital
UNKNOWN
Monash Children's Hospital
UNKNOWN
Women's and Children's Hospital, Australia
OTHER_GOV
Royal Children's Hospital
OTHER
Royal Darwin Hospital
UNKNOWN
M.D. Anderson Cancer Center
OTHER
Virginia Commonwealth University
OTHER
Alberta Children's Hospital
OTHER
British Columbia Children's Hospital
OTHER
Centre Hospitalier Univeritaire Sainte Justine
UNKNOWN
Centre Hospitalier Universitaire de Quebec
UNKNOWN
Children's Hospital of Eastern Ontario
OTHER
The Hospital for Sick Children
OTHER
IWK Health Centre
OTHER
Jim Pattison Children's Hospital
UNKNOWN
Kingston Health Sciences Centre
OTHER
London Health Sciences Centre
OTHER
McMaster Children's Hospital
OTHER
Stollery Children's Hospital
OTHER
The Children's Hospital of Winnipeg
OTHER
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
Pennsylvania Department of Health
OTHER_GOV
Townsville University Hospital
OTHER
Children's Hospital of Philadelphia
OTHER
Responsible Party
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Frances Balamuth
Principal Investigator
Principal Investigators
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Fran Balamuth, MD PhD MSCE
Role: PRINCIPAL_INVESTIGATOR
Attending Physician, Emergency Department
Locations
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UC Davis: University of California, Davis
Davis, California, United States
CHLA: Children's Hospital Los Angeles
Los Angeles, California, United States
UCSF Benioff Children's Hospital
San Francisco, California, United States
Children's Colorado: University of Colorado
Denver, Colorado, United States
Children's Hospital of Atlanta
Emory, Georgia, United States
Lurie Children's: Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Boston Children's Hospital
Boston, Massachusetts, United States
CS Mott Children's Hospital
Ann Arbor, Michigan, United States
Washington University
St Louis, Missouri, United States
Columbia: New York-Presbyterian Hospital
New York, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
Hasbro Children's Hospital
Providence, Rhode Island, United States
Dallas Children's: Children's Medical Center Dallas/UT southwestern
Dallas, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
Primary Children's: University of Utah
Salt Lake City, Utah, United States
Children's Hospital of Richmond at VCU
Richmond, Virginia, United States
Children's National Medical Center
Columbia, Washington, United States
Seattle Children's Hospital
Seattle, Washington, United States
Milwaukee (MCW): Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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References
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Balamuth F, Kittick M, McBride P, Woodford AL, Vestal N, Casper TC, Metheney M, Smith K, Atkin NJ, Baren JM, Dean JM, Kuppermann N, Weiss SL. Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: The PRoMPT BOLUS Randomized Controlled Trial Pilot Feasibility Study. Acad Emerg Med. 2019 Dec;26(12):1346-1356. doi: 10.1111/acem.13815. Epub 2019 Jul 18.
Weiss SL, Balamuth F, Long E, Thompson GC, Hayes KL, Katcoff H, Cook M, Tsemberis E, Hickey CP, Williams A, Williamson-Urquhart S, Borland ML, Dalziel SR, Gelbart B, Freedman SB, Babl FE, Huang J, Kuppermann N; Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks. PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial. Trials. 2021 Nov 6;22(1):776. doi: 10.1186/s13063-021-05717-4.
Other Identifiers
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19-016484
Identifier Type: -
Identifier Source: org_study_id