PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial

for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks

doi:10.1186/s13063-021-05717-4

PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial

for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

23 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	776
Publicación	Trials
Volumen	22
N.º	1
DOI	https://doi.org/10.1186/s13063-021-05717-4
Estado	Published - dic. 2021

Nota bibliográfica

Funding Information:
Funding is provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD101528, Commonwealth of Pennsylvania Department of Health SAP #4100085749, The Medical Research Futures Fund International Clinical Trial Collaboration (APP1190814), and the Canadian Institutes of Health Research 173498. Additional support is provided by The Children’s Hospital of Philadelphia Research Institute and Alberta Children’s Hospital Research Institute. The Pediatric Emergency Care Applied Research Network (PECARN) is funded through the Emergency Medical Services for Children Network Development Demonstration Program of the Maternal and Child Health Bureau, Health Resources and Services Administration, under cooperative agreement (awards U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685). The Pediatric Research in Emergency Departments International Collaborative (PREDICT) Network is funded, in part, through a National Health and Medical Research Council (NHMRC), Canberra, Australia, Centre of Research Excellence Grant (GNT1058560). SRD is partly funded by Cure Kids New Zealand. SF is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness. FEB’s time is part funded by an NHMRC Practitioner Fellowship and the Royal Children’s Hospital Foundation, Melbourne, Australia. The content and conclusions of this article are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by, any funding or governmental agencies. The funding institutions had no role in (1) the conception, design, or conduct of the study; (2) the collection, management, analysis, interpretation, or presentation of the data; or (3) the preparation, review, or approval of the manuscript.

Funding Information:
We thank the global Pediatric Emergency Research Network (PERN) for endorsement of this study. We thank the National Center for Advancing Translational Sciences Trial Innovation Network for consultation in the study design/methods and for providing financial support of the PRoMPT BOLUS pilot and feasibility trial. We thank J. Michael Dean MD, Charlie Casper PhD, SallyJo Zuspan, and Melissa Metheney from the PECARN Data Coordinating Center and Rick Watts from the PERC Data Coordinating Center for their insightful comments and support of this trial. We acknowledge the contributions of Ed Oakley, MBBS FACEM and Sarah McNab, MBBS PhD as members of the Australian and New Zealand steering committee. We also acknowledge review and endorsement of the trial by the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network, Society of Critical Care Medicine Discovery Network, Australian and New Zealand Intensive Care Society Paediatric Study Group, Australasian College of Emergency Medicine Clinical Trials Network, and the Children’s Inpatient Research Collaboration of Australia and New Zealand. Finally, we thank Andrew Costarino, MD for serving as the independent medical monitor for this study.

Funding Information:
We thank the global Pediatric Emergency Research Network (PERN) for endorsement of this study. We thank the National Center for Advancing Translational Sciences Trial Innovation Network for consultation in the study design/methods and for providing financial support of the PRoMPT BOLUS pilot and feasibility trial. We thank J. Michael Dean MD, Charlie Casper PhD, SallyJo Zuspan, and Melissa Metheney from the PECARN Data Coordinating Center and Rick Watts from the PERC Data Coordinating Center for their insightful comments and support of this trial. We acknowledge the contributions of Ed Oakley, MBBS FACEM and Sarah McNab, MBBS PhD as members of the Australian and New Zealand steering committee. We also acknowledge review and endorsement of the trial by the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network, Society of Critical Care Medicine Discovery Network, Australian and New Zealand Intensive Care Society Paediatric Study Group, Australasian College of Emergency Medicine Clinical Trials Network, and the Children?s Inpatient Research Collaboration of Australia and New Zealand. Finally, we thank Andrew Costarino, MD for serving as the independent medical monitor for this study. PRoMPT BOLUS INVESTIGATORS Australia: E. Long, A. Williams, F. Babl (The Royal Children?s Hospital); M. Borland, S. O?Brien (Perth Children?s Hospital); S. Craig, E. Ramaga (Monash Children?s Hospital); A. Kochar, G. Nivea (Women?s and Children?s Hospital); S. Jani, D. Thosar (The Children?s Hospital at Westmead); A. Rao (Sydney Children?s Hospital, Randwick); N. Phillips (Queensland Children?s Hospital); S. George (Gold Coast University Hospital); A. Lithgow, C. Mitchell (Royal Darwin Hospital); Canada: G. Thompson, S. Freedman, S. Williamson-Urquhart, E. Gilad, S. Cooke (Alberta Children?s Hospital); P. Judge, S. Murthy, N. Kissoon (British Columbia Children?s Hospital); W. Alqurashi, F. Alnaji (Children?s Hospital of Eastern Ontario); G. Sangha (Children?s Hospital, London Health Sciences Centre); A. Mater, M, Brashaw (Jim Pattison Children?s Hospital); S. Curtis, A. Joffe (Stollery Children?s Hospital); Y. Shayan, M. Tucci (Centre Hospitalier Universitaire Sainte Justine); K. Gripp (The Children?s Hospital of Winnipeg); S. Berthelot, M. Weiss (Centre Hospitalier de l?Universit? Laval); A. Davis, E. Guifoyle, M. Moretti (Hospital for Sick Children); A. Kam, M. Parker, B. Rochwerg (McMaster Children?s Hospital); J. Emsley, N. Verma (IWK Health Centre); A. Sehgal (Kingston Health Sciences Centre); New Zealand: S. Dalziel, M. Bonisch (Starship Hospital); E. Tan, J. Neutze (Kidz First Children?s Hospital); United States: F. Balamuth, S. Weiss, E. Tsemberis, J. Huang, M. Cook, H. Katcoff, K. Hayes, C. Hickey (The Children?s Hospital of Philadelphia); M. Eisenberg, D. Lewander (Boston Children?s Hospital); C. Morris, D. Hurley; S. Baumer-Mouradian (Medical College of Wisconsin); L. Ambroggio, K. Grice (Children?s Hospital Colorado); A. Festekjian (Children?s Hospital Los Angeles); B. Hickey, R. Sada (Children?s Hospital Pittsburgh); J. Dodson, M. Badawy, C. Lebel, M. Elliott (Children?s Medical Center of Dallas); I. Koutralis, K. Hom (Children?s National Hospital); M. Eckerle, M. Singleton (Cincinnati Children?s Hospital Medical Center); A. Rogers, V. Cervantes (CS Mott Children?s Hospital); S. Duffy, I. Bahamon (Hasbro Children?s Hospital); L. Alpern, A. Sirizi (Ann & Robert H. Lurie Children's Hospital of Chicago); A. Haider Ahmad, A. Rubi Banegas (MD Anderson Cancer Center, Children?s Cancer Hospital); J. Lloyd, K. DiCostanzo (Nationwide Children?s Hospital); M. Kwok, J. Ochs (New York-Presbyterian Morgan Stanley Children?s Hospital); R. Lane, T. Harbour (Primary Children?s Hospital); N. Uspal, K. Cappetto (Seattle Children?s Hospital); L. Clukies, D. Robinson (St. Louis Children?s Hospital); J. McManemy, V. Gonzales (Texas Children?s Hospital); C. Vance, N. Kupperman, K. Pimenta (UC Davis Children?s Hospital), K. Mansour, L. Lavrisha (UCSF Benioff Children?s Hospital); M. Ramirez, J. Grad (NYU Langone Health)

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus Subject Areas

Medicine (miscellaneous)
Pharmacology (medical)

PubMed: MeSH publication types

Clinical Trial Protocol
Journal Article

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10.1186/s13063-021-05717-4

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for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks (2021). PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial. Trials, 22(1), Artículo 776. https://doi.org/10.1186/s13063-021-05717-4

PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial. / for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks.
En: Trials, Vol. 22, N.º 1, 776, 12.2021.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks 2021, 'PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial', Trials, vol. 22, n.º 1, 776. https://doi.org/10.1186/s13063-021-05717-4

@article{638f23397b2b4137a9487cd9b5fb52a2,

title = "PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial",

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.",

author = "{for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks} and Weiss, {Scott L.} and Fran Balamuth and Elliot Long and Thompson, {Graham C.} and Hayes, {Katie L.} and Hannah Katcoff and Marlena Cook and Elena Tsemberis and Hickey, {Christopher P.} and Amanda Williams and Sarah Williamson-Urquhart and Borland, {Meredith L.} and Dalziel, {Stuart R.} and Ben Gelbart and Freedman, {Stephen B.} and Babl, {Franz E.} and Jing Huang and Nathan Kuppermann and E. Long and A. Williams and M. Borland and S. O{\textquoteright}Brien and S. Craig and E. Ramaga and A. Kochar and G. Nivea and S. Jani and D. Thosar and A. Rao and N. Phillips and S. George and A. Lithgow and C. Mitchell and G. Thompson and S. Freedman and S. Williamson-Urquhart and E. Gilad and S. Cooke and P. Judge and S. Murthy and N. Kissoon and W. Alqurashi and F. Alnaji and G. Sangha and A. Mater and M. Brashaw and S. Curtis and A. Joffe and Y. Shayan and J. Emsley",

note = "Funding Information: Funding is provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD101528, Commonwealth of Pennsylvania Department of Health SAP #4100085749, The Medical Research Futures Fund International Clinical Trial Collaboration (APP1190814), and the Canadian Institutes of Health Research 173498. Additional support is provided by The Children{\textquoteright}s Hospital of Philadelphia Research Institute and Alberta Children{\textquoteright}s Hospital Research Institute. The Pediatric Emergency Care Applied Research Network (PECARN) is funded through the Emergency Medical Services for Children Network Development Demonstration Program of the Maternal and Child Health Bureau, Health Resources and Services Administration, under cooperative agreement (awards U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685). The Pediatric Research in Emergency Departments International Collaborative (PREDICT) Network is funded, in part, through a National Health and Medical Research Council (NHMRC), Canberra, Australia, Centre of Research Excellence Grant (GNT1058560). SRD is partly funded by Cure Kids New Zealand. SF is supported by the Alberta Children{\textquoteright}s Hospital Foundation Professorship in Child Health and Wellness. FEB{\textquoteright}s time is part funded by an NHMRC Practitioner Fellowship and the Royal Children{\textquoteright}s Hospital Foundation, Melbourne, Australia. The content and conclusions of this article are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by, any funding or governmental agencies. The funding institutions had no role in (1) the conception, design, or conduct of the study; (2) the collection, management, analysis, interpretation, or presentation of the data; or (3) the preparation, review, or approval of the manuscript. Funding Information: We thank the global Pediatric Emergency Research Network (PERN) for endorsement of this study. We thank the National Center for Advancing Translational Sciences Trial Innovation Network for consultation in the study design/methods and for providing financial support of the PRoMPT BOLUS pilot and feasibility trial. We thank J. Michael Dean MD, Charlie Casper PhD, SallyJo Zuspan, and Melissa Metheney from the PECARN Data Coordinating Center and Rick Watts from the PERC Data Coordinating Center for their insightful comments and support of this trial. We acknowledge the contributions of Ed Oakley, MBBS FACEM and Sarah McNab, MBBS PhD as members of the Australian and New Zealand steering committee. We also acknowledge review and endorsement of the trial by the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network, Society of Critical Care Medicine Discovery Network, Australian and New Zealand Intensive Care Society Paediatric Study Group, Australasian College of Emergency Medicine Clinical Trials Network, and the Children{\textquoteright}s Inpatient Research Collaboration of Australia and New Zealand. Finally, we thank Andrew Costarino, MD for serving as the independent medical monitor for this study. Funding Information: We thank the global Pediatric Emergency Research Network (PERN) for endorsement of this study. We thank the National Center for Advancing Translational Sciences Trial Innovation Network for consultation in the study design/methods and for providing financial support of the PRoMPT BOLUS pilot and feasibility trial. We thank J. Michael Dean MD, Charlie Casper PhD, SallyJo Zuspan, and Melissa Metheney from the PECARN Data Coordinating Center and Rick Watts from the PERC Data Coordinating Center for their insightful comments and support of this trial. We acknowledge the contributions of Ed Oakley, MBBS FACEM and Sarah McNab, MBBS PhD as members of the Australian and New Zealand steering committee. We also acknowledge review and endorsement of the trial by the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network, Society of Critical Care Medicine Discovery Network, Australian and New Zealand Intensive Care Society Paediatric Study Group, Australasian College of Emergency Medicine Clinical Trials Network, and the Children?s Inpatient Research Collaboration of Australia and New Zealand. Finally, we thank Andrew Costarino, MD for serving as the independent medical monitor for this study. PRoMPT BOLUS INVESTIGATORS Australia: E. Long, A. Williams, F. Babl (The Royal Children?s Hospital); M. Borland, S. O?Brien (Perth Children?s Hospital); S. Craig, E. Ramaga (Monash Children?s Hospital); A. Kochar, G. Nivea (Women?s and Children?s Hospital); S. Jani, D. Thosar (The Children?s Hospital at Westmead); A. Rao (Sydney Children?s Hospital, Randwick); N. Phillips (Queensland Children?s Hospital); S. George (Gold Coast University Hospital); A. Lithgow, C. Mitchell (Royal Darwin Hospital); Canada: G. Thompson, S. Freedman, S. Williamson-Urquhart, E. Gilad, S. Cooke (Alberta Children?s Hospital); P. Judge, S. Murthy, N. Kissoon (British Columbia Children?s Hospital); W. Alqurashi, F. Alnaji (Children?s Hospital of Eastern Ontario); G. Sangha (Children?s Hospital, London Health Sciences Centre); A. Mater, M, Brashaw (Jim Pattison Children?s Hospital); S. Curtis, A. Joffe (Stollery Children?s Hospital); Y. Shayan, M. Tucci (Centre Hospitalier Universitaire Sainte Justine); K. Gripp (The Children?s Hospital of Winnipeg); S. Berthelot, M. Weiss (Centre Hospitalier de l?Universit? Laval); A. Davis, E. Guifoyle, M. Moretti (Hospital for Sick Children); A. Kam, M. Parker, B. Rochwerg (McMaster Children?s Hospital); J. Emsley, N. Verma (IWK Health Centre); A. Sehgal (Kingston Health Sciences Centre); New Zealand: S. Dalziel, M. Bonisch (Starship Hospital); E. Tan, J. Neutze (Kidz First Children?s Hospital); United States: F. Balamuth, S. Weiss, E. Tsemberis, J. Huang, M. Cook, H. Katcoff, K. Hayes, C. Hickey (The Children?s Hospital of Philadelphia); M. Eisenberg, D. Lewander (Boston Children?s Hospital); C. Morris, D. Hurley; S. Baumer-Mouradian (Medical College of Wisconsin); L. Ambroggio, K. Grice (Children?s Hospital Colorado); A. Festekjian (Children?s Hospital Los Angeles); B. Hickey, R. Sada (Children?s Hospital Pittsburgh); J. Dodson, M. Badawy, C. Lebel, M. Elliott (Children?s Medical Center of Dallas); I. Koutralis, K. Hom (Children?s National Hospital); M. Eckerle, M. Singleton (Cincinnati Children?s Hospital Medical Center); A. Rogers, V. Cervantes (CS Mott Children?s Hospital); S. Duffy, I. Bahamon (Hasbro Children?s Hospital); L. Alpern, A. Sirizi (Ann & Robert H. Lurie Children's Hospital of Chicago); A. Haider Ahmad, A. Rubi Banegas (MD Anderson Cancer Center, Children?s Cancer Hospital); J. Lloyd, K. DiCostanzo (Nationwide Children?s Hospital); M. Kwok, J. Ochs (New York-Presbyterian Morgan Stanley Children?s Hospital); R. Lane, T. Harbour (Primary Children?s Hospital); N. Uspal, K. Cappetto (Seattle Children?s Hospital); L. Clukies, D. Robinson (St. Louis Children?s Hospital); J. McManemy, V. Gonzales (Texas Children?s Hospital); C. Vance, N. Kupperman, K. Pimenta (UC Davis Children?s Hospital), K. Mansour, L. Lavrisha (UCSF Benioff Children?s Hospital); M. Ramirez, J. Grad (NYU Langone Health) Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1186/s13063-021-05717-4",

language = "English",

volume = "22",

journal = "Trials",

issn = "1745-6215",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis

T2 - study protocol for the PRoMPT BOLUS randomized interventional trial

AU - for the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks

AU - Weiss, Scott L.

AU - Balamuth, Fran

AU - Long, Elliot

AU - Thompson, Graham C.

AU - Hayes, Katie L.

AU - Katcoff, Hannah

AU - Cook, Marlena

AU - Tsemberis, Elena

AU - Hickey, Christopher P.

AU - Williams, Amanda

AU - Williamson-Urquhart, Sarah

AU - Borland, Meredith L.

AU - Dalziel, Stuart R.

AU - Gelbart, Ben

AU - Freedman, Stephen B.

AU - Babl, Franz E.

AU - Huang, Jing

AU - Kuppermann, Nathan

AU - Long, E.

AU - Williams, A.

AU - Borland, M.

AU - O’Brien, S.

AU - Craig, S.

AU - Ramaga, E.

AU - Kochar, A.

AU - Nivea, G.

AU - Jani, S.

AU - Thosar, D.

AU - Rao, A.

AU - Phillips, N.

AU - George, S.

AU - Lithgow, A.

AU - Mitchell, C.

AU - Thompson, G.

AU - Freedman, S.

AU - Williamson-Urquhart, S.

AU - Gilad, E.

AU - Cooke, S.

AU - Judge, P.

AU - Murthy, S.

AU - Kissoon, N.

AU - Alqurashi, W.

AU - Alnaji, F.

AU - Sangha, G.

AU - Mater, A.

AU - Brashaw, M.

AU - Curtis, S.

AU - Joffe, A.

AU - Shayan, Y.

AU - Emsley, J.

N1 - Funding Information: Funding is provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD101528, Commonwealth of Pennsylvania Department of Health SAP #4100085749, The Medical Research Futures Fund International Clinical Trial Collaboration (APP1190814), and the Canadian Institutes of Health Research 173498. Additional support is provided by The Children’s Hospital of Philadelphia Research Institute and Alberta Children’s Hospital Research Institute. The Pediatric Emergency Care Applied Research Network (PECARN) is funded through the Emergency Medical Services for Children Network Development Demonstration Program of the Maternal and Child Health Bureau, Health Resources and Services Administration, under cooperative agreement (awards U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685). The Pediatric Research in Emergency Departments International Collaborative (PREDICT) Network is funded, in part, through a National Health and Medical Research Council (NHMRC), Canberra, Australia, Centre of Research Excellence Grant (GNT1058560). SRD is partly funded by Cure Kids New Zealand. SF is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness. FEB’s time is part funded by an NHMRC Practitioner Fellowship and the Royal Children’s Hospital Foundation, Melbourne, Australia. The content and conclusions of this article are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by, any funding or governmental agencies. The funding institutions had no role in (1) the conception, design, or conduct of the study; (2) the collection, management, analysis, interpretation, or presentation of the data; or (3) the preparation, review, or approval of the manuscript. Funding Information: We thank the global Pediatric Emergency Research Network (PERN) for endorsement of this study. We thank the National Center for Advancing Translational Sciences Trial Innovation Network for consultation in the study design/methods and for providing financial support of the PRoMPT BOLUS pilot and feasibility trial. We thank J. Michael Dean MD, Charlie Casper PhD, SallyJo Zuspan, and Melissa Metheney from the PECARN Data Coordinating Center and Rick Watts from the PERC Data Coordinating Center for their insightful comments and support of this trial. We acknowledge the contributions of Ed Oakley, MBBS FACEM and Sarah McNab, MBBS PhD as members of the Australian and New Zealand steering committee. We also acknowledge review and endorsement of the trial by the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network, Society of Critical Care Medicine Discovery Network, Australian and New Zealand Intensive Care Society Paediatric Study Group, Australasian College of Emergency Medicine Clinical Trials Network, and the Children’s Inpatient Research Collaboration of Australia and New Zealand. Finally, we thank Andrew Costarino, MD for serving as the independent medical monitor for this study. Funding Information: We thank the global Pediatric Emergency Research Network (PERN) for endorsement of this study. We thank the National Center for Advancing Translational Sciences Trial Innovation Network for consultation in the study design/methods and for providing financial support of the PRoMPT BOLUS pilot and feasibility trial. We thank J. Michael Dean MD, Charlie Casper PhD, SallyJo Zuspan, and Melissa Metheney from the PECARN Data Coordinating Center and Rick Watts from the PERC Data Coordinating Center for their insightful comments and support of this trial. We acknowledge the contributions of Ed Oakley, MBBS FACEM and Sarah McNab, MBBS PhD as members of the Australian and New Zealand steering committee. We also acknowledge review and endorsement of the trial by the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network, Society of Critical Care Medicine Discovery Network, Australian and New Zealand Intensive Care Society Paediatric Study Group, Australasian College of Emergency Medicine Clinical Trials Network, and the Children?s Inpatient Research Collaboration of Australia and New Zealand. Finally, we thank Andrew Costarino, MD for serving as the independent medical monitor for this study. PRoMPT BOLUS INVESTIGATORS Australia: E. Long, A. Williams, F. Babl (The Royal Children?s Hospital); M. Borland, S. O?Brien (Perth Children?s Hospital); S. Craig, E. Ramaga (Monash Children?s Hospital); A. Kochar, G. Nivea (Women?s and Children?s Hospital); S. Jani, D. Thosar (The Children?s Hospital at Westmead); A. Rao (Sydney Children?s Hospital, Randwick); N. Phillips (Queensland Children?s Hospital); S. George (Gold Coast University Hospital); A. Lithgow, C. Mitchell (Royal Darwin Hospital); Canada: G. Thompson, S. Freedman, S. Williamson-Urquhart, E. Gilad, S. Cooke (Alberta Children?s Hospital); P. Judge, S. Murthy, N. Kissoon (British Columbia Children?s Hospital); W. Alqurashi, F. Alnaji (Children?s Hospital of Eastern Ontario); G. Sangha (Children?s Hospital, London Health Sciences Centre); A. Mater, M, Brashaw (Jim Pattison Children?s Hospital); S. Curtis, A. Joffe (Stollery Children?s Hospital); Y. Shayan, M. Tucci (Centre Hospitalier Universitaire Sainte Justine); K. Gripp (The Children?s Hospital of Winnipeg); S. Berthelot, M. Weiss (Centre Hospitalier de l?Universit? Laval); A. Davis, E. Guifoyle, M. Moretti (Hospital for Sick Children); A. Kam, M. Parker, B. Rochwerg (McMaster Children?s Hospital); J. Emsley, N. Verma (IWK Health Centre); A. Sehgal (Kingston Health Sciences Centre); New Zealand: S. Dalziel, M. Bonisch (Starship Hospital); E. Tan, J. Neutze (Kidz First Children?s Hospital); United States: F. Balamuth, S. Weiss, E. Tsemberis, J. Huang, M. Cook, H. Katcoff, K. Hayes, C. Hickey (The Children?s Hospital of Philadelphia); M. Eisenberg, D. Lewander (Boston Children?s Hospital); C. Morris, D. Hurley; S. Baumer-Mouradian (Medical College of Wisconsin); L. Ambroggio, K. Grice (Children?s Hospital Colorado); A. Festekjian (Children?s Hospital Los Angeles); B. Hickey, R. Sada (Children?s Hospital Pittsburgh); J. Dodson, M. Badawy, C. Lebel, M. Elliott (Children?s Medical Center of Dallas); I. Koutralis, K. Hom (Children?s National Hospital); M. Eckerle, M. Singleton (Cincinnati Children?s Hospital Medical Center); A. Rogers, V. Cervantes (CS Mott Children?s Hospital); S. Duffy, I. Bahamon (Hasbro Children?s Hospital); L. Alpern, A. Sirizi (Ann & Robert H. Lurie Children's Hospital of Chicago); A. Haider Ahmad, A. Rubi Banegas (MD Anderson Cancer Center, Children?s Cancer Hospital); J. Lloyd, K. DiCostanzo (Nationwide Children?s Hospital); M. Kwok, J. Ochs (New York-Presbyterian Morgan Stanley Children?s Hospital); R. Lane, T. Harbour (Primary Children?s Hospital); N. Uspal, K. Cappetto (Seattle Children?s Hospital); L. Clukies, D. Robinson (St. Louis Children?s Hospital); J. McManemy, V. Gonzales (Texas Children?s Hospital); C. Vance, N. Kupperman, K. Pimenta (UC Davis Children?s Hospital), K. Mansour, L. Lavrisha (UCSF Benioff Children?s Hospital); M. Ramirez, J. Grad (NYU Langone Health) Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85118785069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85118785069&partnerID=8YFLogxK

U2 - 10.1186/s13063-021-05717-4

DO - 10.1186/s13063-021-05717-4

M3 - Article

C2 - 34742327

AN - SCOPUS:85118785069

SN - 1745-6215

VL - 22

JO - Trials

JF - Trials

IS - 1

M1 - 776

ER -

PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial

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