PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial
Scott L. Weiss,
Fran Balamuth,
Elliot Long,
Graham C. Thompson,
Katie L. Hayes,
Hannah Katcoff,
Marlena Cook,
Elena Tsemberis,
Christopher P. Hickey,
Amanda Williams,
Sarah Williamson-Urquhart,
Meredith L. Borland,
Stuart R. Dalziel,
Ben Gelbart,
Stephen B. Freedman,
Franz E. Babl,
Jing Huang,
Nathan Kuppermann,
for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks
Affiliations
Scott L. Weiss
Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania
Fran Balamuth
The Children’s Hospital of Philadelphia Pediatric Sepsis Program
Elliot Long
Department of Emergency Medicine, The Royal Children’s Hospital
Graham C. Thompson
Departments of Pediatrics and Emergency Medicine, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary
Katie L. Hayes
The Children’s Hospital of Philadelphia Pediatric Sepsis Program
Hannah Katcoff
Department of Biomedical and Health Informatics, Data Science and Biostatistics Unit, The Children’s Hospital of Philadelphia
Marlena Cook
Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania
Elena Tsemberis
Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania
Christopher P. Hickey
The Children’s Hospital of Philadelphia Pediatric Sepsis Program
Amanda Williams
Department of Emergency Medicine, The Royal Children’s Hospital
Sarah Williamson-Urquhart
Departments of Pediatrics and Emergency Medicine, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary
Meredith L. Borland
Divisions of Emergency Medicine and Pediatrics, Perth Children’s Hospital, School of Medicine at the University of Western Australia
Stuart R. Dalziel
Departments of Surgery and Pediatrics: Child and Youth Health, Starship Children’s Hospital, University of Auckland
Ben Gelbart
Departments of Pediatrics and Critical Care, The University of Melbourne
Stephen B. Freedman
Sections of Pediatric Emergency Medicine and Gastroenterology, Departments of Pediatrics and Emergency Medicine, Cumming School of Medicine, University of Calgary
Franz E. Babl
Department of Emergency Medicine, The Royal Children’s Hospital
Jing Huang
Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania
Nathan Kuppermann
Department of Emergency Medicine and Pediatrics, UC Davis School of medicine and UC Davis Health
for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks
Abstract Background/aims Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock. Methods The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under “exception from informed consent” in the USA or “deferred consent” in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed. Discussion PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings. Trial registration PRoMPT BOLUS was first registered at ClinicalTrials.gov ( NCT04102371 ) on September 25, 2019. Enrollment started on August 25, 2020.
