ShockPhase 3PRoMPT BOLUSNCT04102371
Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis
A Phase 3 study testing Lactated Ringer, Normal Saline and Plasma-lyte in people with Shock and Septic, run by Children's Hospital of Philadelphia at 22 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 months to 17 years
- What is being tested?
- Lactated Ringer, Normal Saline and Plasma-lyte
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9,041 participants
- Where
- 22 sitesUnited States
- Study dates
- 25 Aug 2020to 31 Jan 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
CS Mott Children's Hospital
Ann Arbor, Michigan, 48109
Boston Children's Hospital
Boston, Massachusetts, 02115
Lurie Children's: Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's National Medical Center
Columbia, Washington, 20010
Nationwide Children's Hospital
Columbus, Ohio, 43205
Dallas Children's: Children's Medical Center Dallas/UT southwestern
Dallas, Texas, 75235
UC Davis: University of California, Davis
Davis, California, 95616
Children's Colorado: University of Colorado
Denver, Colorado, 80204
Children's Hospital of Atlanta
Emory, Georgia, 30322
Texas Children's Hospital
Houston, Texas, 77030
CHLA: Children's Hospital Los Angeles
Los Angeles, California, 90027
Milwaukee (MCW): Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia: New York-Presbyterian Hospital
New York, New York, 10065-4870
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Hasbro Children's Hospital
Providence, Rhode Island, 02903
Children's Hospital of Richmond at VCU
Richmond, Virginia, 23284
Primary Children's: University of Utah
Salt Lake City, Utah, 84113
UCSF Benioff Children's Hospital
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University
St Louis, Missouri, 63130
About this study
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.
Read the detailed description
Approximately 5,000 children die from septic shock each year in the United States (US); thousands more die worldwide. Most children admitted with sepsis receive initial resuscitation in an emergency department (ED), where septic shock remains one of the most critical of illnesses treated by ED clinicians. Sepsis is also the most expensive hospital condition in the US, and the most common cause of pediatric multiple organ dysfunction syndrome (MODS). While all crystalloid fluids help to reverse shock, the most effective and safest type of crystalloid fluid resuscitation is unknown.
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.
- Being tested
- Lactated Ringer, Normal Saline, Plasma-lyte
- Keywords
- Sepsis, Septic Shock, Fluid resuscitation, Saline, Balanced Fluid, Mortality, Crystalloid, PlasmaLyte, Lactated Ringer's, Kidney injury
- Medical subject headings
- Shock, Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactated RingerDrug
Also called LR
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 SalineDrug
Also called 0.9% Saline, NS
Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
Plasma-lyteDrug
Also called PL
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).
| Study group | Role | What they receive |
|---|---|---|
| Balanced fluids (BF) | Experimental | 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. Receives: Drug: Lactated Ringer; Drug: Plasma-lyte |
| 0.9% "Normal" Saline Fluid (NS) | Active comparator | 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. Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Between randomization and 30 days post enrollment, discharge or death, whichever comes first.
Secondary outcomes (14)
Proportion of participants with persistent kidney dysfunction
Final creatinine greater than or equal to 200% of baseline and a minimum absolute increase of greater than or equal to 0.3 mg/dL
Measured: Censored at 30 days
Proportion of participants with new inpatient renal replacement therapy
Treatment with any renal replacement therapy that was not a continuation of pre-hospital chronic therapy
Measured: Censored at 30 days
Hospital-free days alive between randomization and day 27
Calendar days alive and out of the hospital between day of randomization and study day 27
Measured: With 27 days of randomization
Proportion of participants with all-cause hospital mortality
Vital status at hospital discharge
Measured: Hospital discharge-censored at 90 days
Proportion of participants with all-cause mortality at 90 days
Vital status from medical chart and/or data from National Death Index
Measured: 90 days
Proportion of participants with hyperlactatemia
At least 1 venous or arterial blood lactate measurement >4mmol/L
Measured: Within 4 calendar days of randomization
Proportion of participants with hyperkalemia
At least 1 venous or arterial blood potassium measurement >6 milliequivalents/Liter (mEq/L) (without hemolysis)
Measured: Within 4 calendar days of randomization
Proportion of participants with hypercalcemia
At least 1 venous or arterial blood ionized calcium measurement of >1.35 mEq/L or total calcium >12 mEq/L
Measured: Within 4 calendar days of randomization
Proportion of participants with hypernatremia
At least 1 venous, arterial or capillary blood sodium measurement of >155 mEq/L
Measured: Within 4 calendar days of randomization
Proportion of participants with hyponatremia
At least 1 venous, arterial or capillary blood sodium measurement of <128 mEq/L
Measured: Within 4 calendar days of randomization
Proportion of participants with hyperchloremia
At least 1 venous, arterial or capillary blood chloride measurement of >110 mEq/L
Measured: Within 4 calendar days of randomization
Proportion of participants with catheter thrombosis
Catheter thrombosis in participants given Ceftriaxone and BF? (not LR?)
Measured: Within 4 calendar days of randomization
Proportion of participants with brain herniation
Treatment with hyperosmolar therapy (as long as a clinical diagnosis of brain herniation is not disproven by radiographic studies)
Measured: Within 4 calendar days of randomization
Proportion of participants with thromboembolism
Therapy for thromboembolism
Measured: Within 7 calendar days of randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2019
- Study start25 Aug 2020
- Primary completion1 Dec 2025
- Study completion31 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ShockStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multi-center, open-label, randomized pragmatic comparative effectiveness trial.
- Masking
- None (open label)
- Enrolment
- 9,041 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Children's Hospital, Children's Healthcare of Atlanta, Children's Hospital Colorado, Children's Hospital Los Angeles, University of Pittsburgh, Children's Hospital and Health System Foundation, Wisconsin, Children's Medical Center Dallas, Children's National Research Institute, Children's Hospital Medical Center, Cincinnati, Hasbro Children's Hospital, Ann & Robert H Lurie Children's Hospital of Chicago, Nationwide Children's Hospital, Primary Children's Hospital, Seattle Children's Hospital, St. Louis Children's Hospital, Baylor College of Medicine, University of California, Davis, University of California, San Francisco, University of Michigan, Kidz First Hospital Middlemore, Gold Coast Hospital and Health Service, Queensland Children's Hospital, Westmead Children's Hospital, Sydney Children's Hospitals Network, Perth Children's Hospital, Starship Children's Hospital, Monash Children's Hospital, Women's and Children's Hospital, Australia, Royal Children's Hospital, Royal Darwin Hospital, Virginia Commonwealth University, Alberta Children's Hospital, British Columbia Children's Hospital, Centre Hospitalier Univeritaire Sainte Justine, Centre Hospitalier Universitaire de Quebec, Children's Hospital of Eastern Ontario, The Hospital for Sick Children, IWK Health Centre, Jim Pattison Children's Hospital, Kingston Health Sciences Centre, London Health Sciences Centre, McMaster Children's Hospital, Stollery Children's Hospital, The Children's Hospital of Winnipeg, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Pennsylvania Department of Health, Townsville University Hospital, Hospital nacional de niños Costa Rica, Morgan Stanley Children's Hospital
- Responsible party
- Principal investigator, Frances Balamuth, Children's Hospital of Philadelphia
- Investigators
- Fran Balamuth, MD PhD MSCE, Principal investigator, Attending Physician, Emergency Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04102371
- Sponsor's protocol ID
- 19-016484
- Other IDs
- R01HD101528
- Acronym
- PRoMPT BOLUS
- Status last verified
- Mar 2026
- First submitted
- 23 Sep 2019
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 31183919Balamuth F, Weiss SL, Long E, Thompson GC, Artis AS, Campos AB, Borland ML, Dalziel SR, Yock-Corrales A, Singh R, Williams A, Mickiewicz B, Hickey CP, Fitzgerald JC, Laskin BL, Hickey RW, Eckerle M, Alqurashi W, Alpern E, Ambroggio L, Badawy M, Baumer-Mouradian S, Berthelot S, Clukies LD, Craig S, Curtis SJ, Davis AL, Duffy S, Eisenberg MA, Emsley JG, Festekjian A, George S, Green R, Gripp KE, Jain PG, Jani S, Joubert GI, Judge P, Kam A, Kochar A, Koutroulis I, Kwok MY, Lane RD, Lithgow A, Lloyd J, Mansour K, McManemy JK, Morris C, Phillips N, Rao A, Rogers A, Sehgal A, Shayan Y, Silverman J, Tan E, Uspal NG, Vance C, Whyte E, Huang J, Freedman SB, Babl FE, Kuppermann N; PRoMPT BOLUS Investigators of the PECARN, PERC, and PREDICT Networks. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. N Engl J Med. 2026 Apr 24:10.1056/NEJMoa2601969. doi: 10.1056/NEJMoa2601969. Online ahead of print.
PubMed 42028918Weiss 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.
PubMed 34742327
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis
- ClinicalTrials.gov ID
- NCT04102371
- Acronym / sponsor ID
- PRoMPT BOLUS / 19-016484
- Keywords
- Sepsis, Septic Shock, Fluid resuscitation, Saline, Balanced Fluid, Mortality, Crystalloid, PlasmaLyte
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9,041 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Boston Children's Hospital, Children's Healthcare of Atlanta, Children's Hospital Colorado, Children's Hospital Los Angeles, University of Pittsburgh, Children's Hospital and Health System Foundation, Wisconsin, Children's Medical Center Dallas, Children's National Research Institute, Children's Hospital Medical Center, Cincinnati, Hasbro Children's Hospital, Ann & Robert H Lurie Children's Hospital of Chicago, Nationwide Children's Hospital, Primary Children's Hospital, Seattle Children's Hospital, St. Louis Children's Hospital, Baylor College of Medicine, University of California, Davis, University of California, San Francisco, University of Michigan, Kidz First Hospital Middlemore, Gold Coast Hospital and Health Service, Queensland Children's Hospital, Westmead Children's Hospital, Sydney Children's Hospitals Network, Perth Children's Hospital, Starship Children's Hospital, Monash Children's Hospital, Women's and Children's Hospital, Australia, Royal Children's Hospital, Royal Darwin Hospital, Virginia Commonwealth University, Alberta Children's Hospital, British Columbia Children's Hospital, Centre Hospitalier Univeritaire Sainte Justine, Centre Hospitalier Universitaire de Quebec, Children's Hospital of Eastern Ontario, The Hospital for Sick Children, IWK Health Centre, Jim Pattison Children's Hospital, Kingston Health Sciences Centre, London Health Sciences Centre, McMaster Children's Hospital, Stollery Children's Hospital, The Children's Hospital of Winnipeg, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Pennsylvania Department of Health, Townsville University Hospital, Hospital nacional de niños Costa Rica, Morgan Stanley Children's Hospital
- Study start
- 25 Aug 2020 (actual)
- Primary completion
- 1 Dec 2025 (actual)
- Study completion
- 31 Jan 2026 (actual)
- First posted
- 25 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Approximately 5,000 children die from septic shock each year in the United States (US); thousands more die worldwide. Most children admitted with sepsis receive initial resuscitation in an emergency department (ED), where septic shock remains one of the most critical of illnesses treated by ED clinicians. Sepsis is also the most expensive hospital condition in the US, and the most common cause of pediatric multiple organ dysfunction syndrome (MODS). While all crystalloid fluids help to reverse shock, the most effective and safest type of crystalloid fluid resuscitation is unknown.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multi-center, open-label, randomized pragmatic comparative effectiveness trial.
| Arm | Type | Receives |
|---|---|---|
| Balanced fluids (BF) | Experimental | Drug: Lactated Ringer, Drug: Plasma-lyteBalanced 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 comparator | Drug: Normal Saline0.9% "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. |
Who may qualify
- Ages
- 2 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Males or females age >2 months to <18 years
- Clinician concern for septic shock, operationalized as:
- 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
Key exclusion criteria (13 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactated RingerAlso: LRLR 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). | Drug | Balanced fluids (BF) |
| Normal SalineAlso: 0.9% Saline, NSNormal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride. | Drug | 0.9% "Normal" Saline Fluid (NS) |
| Plasma-lyteAlso: PLPL 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). | Drug | Balanced fluids (BF) |
Primary outcome
Proportion of participants with Major Adverse Kidney Events within 30 days (MAKE30)
Time frame: Between randomization and 30 days post enrollment, discharge or death, whichever comes first.
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.
14 secondary outcomes
Proportion of participants with persistent kidney dysfunction
Time frame: Censored at 30 days
Proportion of participants with new inpatient renal replacement therapy
Time frame: Censored at 30 days
Hospital-free days alive between randomization and day 27
Time frame: With 27 days of randomization
Proportion of participants with all-cause hospital mortality
Time frame: Hospital discharge-censored at 90 days
Proportion of participants with all-cause mortality at 90 days
Time frame: 90 days
Proportion of participants with hyperlactatemia
Time frame: Within 4 calendar days of randomization
Proportion of participants with hyperkalemia
Time frame: Within 4 calendar days of randomization
Proportion of participants with hypercalcemia
Time frame: Within 4 calendar days of randomization
Proportion of participants with hypernatremia
Time frame: Within 4 calendar days of randomization
Proportion of participants with hyponatremia
Time frame: Within 4 calendar days of randomization
Proportion of participants with hyperchloremia
Time frame: Within 4 calendar days of randomization
Proportion of participants with catheter thrombosis
Time frame: Within 4 calendar days of randomization
Proportion of participants with brain herniation
Time frame: Within 4 calendar days of randomization
Proportion of participants with thromboembolism
Time frame: Within 7 calendar days of randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Background: PubMed 31183919Balamuth 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.
- Derived from this study: PubMed 42028918Balamuth F, Weiss SL, Long E, Thompson GC, Artis AS, Campos AB, Borland ML, Dalziel SR, Yock-Corrales A, Singh R, Williams A, Mickiewicz B, Hickey CP, Fitzgerald JC, Laskin BL, Hickey RW, Eckerle M, Alqurashi W, Alpern E, Ambroggio L, Badawy M, Baumer-Mouradian S, Berthelot S, Clukies LD, Craig S, Curtis SJ, Davis AL, Duffy S, Eisenberg MA, Emsley JG, Festekjian A, George S, Green R, Gripp KE, Jain PG, Jani S, Joubert GI, Judge P, Kam A, Kochar A, Koutroulis I, Kwok MY, Lane RD, Lithgow A, Lloyd J, Mansour K, McManemy JK, Morris C, Phillips N, Rao A, Rogers A, Sehgal A, Shayan Y, Silverman J, Tan E, Uspal NG, Vance C, Whyte E, Huang J, Freedman SB, Babl FE, Kuppermann N; PRoMPT BOLUS Investigators of the PECARN, PERC, and PREDICT Networks. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. N Engl J Med. 2026 Apr 24:10.1056/NEJMoa2601969. doi: 10.1056/NEJMoa2601969. Online ahead of print.
- Derived from this study: PubMed 34742327Weiss 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fran Balamuth, MD PhD MSCE principal investigator
Attending Physician, Emergency Department
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lactated Ringer, Normal Saline and Plasma-lyte in people with Shock and Septic, run by Children's Hospital of Philadelphia at 22 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with Major Adverse Kidney Events within 30 days (MAKE30) (time frame: Between randomization and 30 days post enrollment, discharge or death, whichever comes first.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04102371, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.