Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis
PRoMPT BOLUS
2 other identifiers
interventional
9,041
1 country
22
Brief Summary
The objectives of this multicenter pragmatic clinical trial are to compare the effectiveness and relative safety of balanced fluid resuscitation versus 0.9% "normal" saline in children with septic shock, including whether balanced fluid resuscitation can reduce progression of kidney injury.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2020
Longer than P75 for phase_3
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2019
CompletedFirst Posted
Study publicly available on registry
September 25, 2019
CompletedStudy Start
First participant enrolled
August 25, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2026
CompletedMarch 5, 2026
March 1, 2026
5.3 years
September 23, 2019
March 3, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of participants with Major Adverse Kidney Events within 30 days (MAKE30)
A composite of death, initiation of new inpatient renal replacement therapy (RRT), or persistent kidney dysfunction, at 30 days following study enrollment or hospital discharge, whichever comes first.
Between randomization and 30 days post enrollment, discharge or death, whichever comes first.
Secondary Outcomes (14)
Proportion of participants with persistent kidney dysfunction
Censored at 30 days
Proportion of participants with new inpatient renal replacement therapy
Censored at 30 days
Hospital-free days alive between randomization and day 27
With 27 days of randomization
Proportion of participants with all-cause hospital mortality
Hospital discharge-censored at 90 days
Proportion of participants with all-cause mortality at 90 days
90 days
- +9 more secondary outcomes
Other Outcomes (1)
Kidney biomarkers measured from blood and urine samples
Day 2 and Day 27, prior to anticipated discharge or death, whichever comes first.
Study Arms (2)
Balanced fluids (BF)
EXPERIMENTALBalanced 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.
0.9% "Normal" Saline Fluid (NS)
ACTIVE COMPARATOR0.9% "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.
Interventions
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 solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
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).
Eligibility Criteria
You may qualify if:
- Males or females age \>2 months to \<18 years
- Clinician concern for septic shock, operationalized as:
- a "positive" ED sepsis alert confirmed by a physician OR
- physician decision to treat for septic shock OR
- a physician diagnosis of septic shock requiring parenteral antibiotics and fluid resuscitation
- 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.
- Receipt of ≤40 mL/kg IV/IO total crystalloid fluid prior to randomization
- Parental/guardian permission (informed consent) if time permits; otherwise, Exception from informed consent (EFIC) criteria met
You may not qualify if:
- Treating physician judges that patient's condition deems it unsafe to administer either NS or BF (since patients will be equally likely to receive NS or BF at time of study enrollment), including:
- Clinical suspicion for impending brain herniation
- 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
- 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
- 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
- Known history of severe hepatic impairment, defined as cirrhosis, "liver failure", or awaiting transplant
- Known history of severe renal impairment, defined as peritoneal dialysis or hemodialysis
- 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
- Other concern for which the treating clinician deems it unsafe to administer either NS or LR
- Known pregnancy determined by routine history disclosed by patient and/or accompanying acquaintance.
- Known prisoner
- Known allergy to a crystalloid fluid
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Healthcare of Atlantacollaborator
- Women's and Children's Hospital, Australiacollaborator
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)collaborator
- Children's Hospital of Philadelphialead
- Boston Children's Hospitalcollaborator
- Children's Hospital Coloradocollaborator
- Children's Hospital Los Angelescollaborator
- University of Pittsburghcollaborator
- Children's Hospital and Health System Foundation, Wisconsincollaborator
- Children's Medical Center Dallascollaborator
- Children's National Research Institutecollaborator
- Children's Hospital Medical Center, Cincinnaticollaborator
- Hasbro Children's Hospitalcollaborator
- Ann & Robert H Lurie Children's Hospital of Chicagocollaborator
- Nationwide Children's Hospitalcollaborator
- Primary Children's Hospitalcollaborator
- Seattle Children's Hospitalcollaborator
- St. Louis Children's Hospitalcollaborator
- Baylor College of Medicinecollaborator
- University of California, Daviscollaborator
- University of California, San Franciscocollaborator
- University of Michigancollaborator
- Kidz First Hospital Middlemorecollaborator
- Gold Coast Hospital and Health Servicecollaborator
- Queensland Children's Hospitalcollaborator
- Westmead Children's Hospitalcollaborator
- Sydney Children's Hospitals Networkcollaborator
- Perth Children's Hospitalcollaborator
- Starship Children's Hospitalcollaborator
- Monash Children's Hospitalcollaborator
- Royal Children's Hospitalcollaborator
- Royal Darwin Hospitalcollaborator
- Virginia Commonwealth Universitycollaborator
- Alberta Children's Hospitalcollaborator
- British Columbia Children's Hospitalcollaborator
- Centre Hospitalier Univeritaire Sainte Justinecollaborator
- Centre Hospitalier Universitaire de Quebeccollaborator
- Children's Hospital of Eastern Ontariocollaborator
- The Hospital for Sick Childrencollaborator
- IWK Health Centrecollaborator
- Jim Pattison Children's Hospitalcollaborator
- Kingston Health Sciences Centrecollaborator
- London Health Sciences Centrecollaborator
- McMaster Children's Hospitalcollaborator
- Stollery Children's Hospitalcollaborator
- The Children's Hospital of Winnipegcollaborator
- Pennsylvania Department of Healthcollaborator
- Townsville University Hospitalcollaborator
- Hospital nacional de niños Costa Ricacollaborator
- Morgan Stanley Children's Hospitalcollaborator
Study Sites (22)
UC Davis: University of California, Davis
Davis, California, 95616, United States
CHLA: Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
UCSF Benioff Children's Hospital
San Francisco, California, 94143, United States
Children's Colorado: University of Colorado
Denver, Colorado, 80204, United States
Children's Hospital of Atlanta
Emory, Georgia, 30322, United States
Lurie Children's: Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
CS Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Washington University
St Louis, Missouri, 63130, United States
Columbia: New York-Presbyterian Hospital
New York, New York, 10065-4870, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
Hasbro Children's Hospital
Providence, Rhode Island, 02903, United States
Dallas Children's: Children's Medical Center Dallas/UT southwestern
Dallas, Texas, 75235, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Primary Children's: University of Utah
Salt Lake City, Utah, 84113, United States
Children's Hospital of Richmond at VCU
Richmond, Virginia, 23284, United States
Children's National Medical Center
Columbia, Washington, 20010, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Milwaukee (MCW): Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (2)
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.
PMID: 31183919BACKGROUNDWeiss 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.
PMID: 34742327DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Fran Balamuth, MD PhD MSCE
Attending Physician, Emergency Department
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 23, 2019
First Posted
September 25, 2019
Study Start
August 25, 2020
Primary Completion
December 1, 2025
Study Completion
January 31, 2026
Last Updated
March 5, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- No later than 3 years after the final 90-day assessment or 2 years after the primary paper has been published, whichever comes first.
- Access Criteria
- Anyone can access NICHD DASH, which is a public website with free access to the scientific research community. All users may browse and view information about studies and data archived in NICHD DASH. Users who are interested in submitting or requesting study data must register for a free account.
Per NIH policy, the PRoMPT BOLUS investigators will provide a de-identified dataset and documentation necessary to utilize the study data (dictionary, calculated variables, and standard operating procedures) to the NIH no later than 3 years after the final 90-day assessment or 2 years after the primary paper has been published, whichever comes first. The investigators will submit this dataset to the National Institute of Child Health and Human Development (NICHD) data repository, Data and Specimen Hub (DASH). In addition, final datasets and statistical analyses will be archived.