PRagMatic Pediatric Trial of Balanced versus NOrmaL Saline FlUid in Sepsis (PRoMPT BOLUS)

Project Summary
Sepsis is a medical emergency defined as life-threatening organ dysfunction due to a dysregulated host
response to infection. Septic shock is the most severe form, involving cardiovascular failure. More than
75,000 children in the US and four million children worldwide are hospitalized with sepsis or septic shock every
year. Sepsis is currently the most expensive hospital condition in the US and, for critically ill patients—
including children—is the most common cause of multiple organ dysfunction syndrome and hospital death.1,26
The World Health Organization and the US Centers for Disease Control and Prevention have called for
optimizing therapies for sepsis.33 Because fluid resuscitation provides the best established benefit for septic
shock (other than antibiotics), there has been an effort to identify the most effective fluid administration
strategy. Despite progress, a remaining key gap in knowledge delineated by the Surviving Sepsis Campaign is
which crystalloid fluid is the most effective and safest to use for initial resuscitation of septic shock.
Two types of crystalloids are used for resuscitation in sepsis: 0.9% “normal” saline (NS) and balanced fluids
(BF). BF have well-established biologic and physiologic advantages over NS and two recent adult trials found
that BF reduced major adverse kidney events and mortality. However, in the absence of pediatric-specific
data, NS resuscitation remains the overwhelming preference among pediatric emergency clinicians. We
therefore propose the PRagMatic Pediatric Trial of Balanced versus NOrmaL Saline FlUid in Sepsis (PRoMPT
BOLUS) study, a randomized, open-label, pragmatic comparative effectiveness trial, to test the relative
effectiveness and safety of BF versus NS fluid resuscitation in children with suspected septic shock. Eighteen
pediatric emergency departments in the Pediatric Emergency Care Applied Research Network (PECARN) will
collaborate with sites in Canada, Australia, and New Zealand to enroll 8,800 children with suspected septic
shock. Eligible patients will be enrolled either through prospective informed consent or, after appropriate
ethical safeguards, “Exception From Informed Consent” for emergency research. Subjects will be randomized
to fluid resuscitation and maintenance fluids with either NS or BF for 24-48 hours, with all aspects of care other
than fluid type at the discretion of the care team. Our primary outcome is major adverse kidney events within
30 days from randomization (MAKE30), a patient-centered composite endpoint that includes persistent kidney
dysfunction, initiation of dialysis, or death. This outcome addresses the biological advantages of BF to
preserve renal blood flow and function compared to NS. Secondary outcomes include the individual
components of MAKE30, hospital-free days, length of stay, 90-day mortality, and specified safety events.
This pragmatic trial will provide the definitive evidence necessary for a “paradigm shift” to move
clinical practice from 0.9% saline to balanced fluid-based resuscitation in children with septic shock.

Grant Number: 5R01HD101528-05
NIH Institute/Center: NIH
Principal Investigator: Frances Balamuth