PRoMPT BOLUS Australia and New Zealand
- Project status: Active
Research area: Clinical Sciences > Emergency
PRagMatic paediatric trial of balanced vs normal saline fluid in sepsis (PRoMPT BOLUS).
PRoMPT BOLUS is a large clinical trial that will enrol over 8,000 children with sepsis across the United States, Canada, Australia, and New Zealand.
PRoMPT BOLUS is a large clinical trial that will enrol over 8,000 children with sepsis across the United States, Canada, Australia, and New Zealand.
Overview
The goal of PRoMPT BOLUS is to compare 0.9% saline and balanced fluids that are currently both used in routine clinical care. Both fluids are commonly used, and both are helpful to treat paediatric sepsis, but we do not yet know which fluid is the safest and most effective.
PRoMPT BOLUS is a pragmatic clinical trial, so the study conditions mimic “real life” as much as possible with simple inclusion criteria, few exclusion criteria, and very few elements of care that are protocolised. PRoMPT BOLUS is a large clinical trial that will enrol over 8,000 children with sepsis across the United States, Canada, Australia, and New Zealand.
PRoMPT BOLUS Study
Find out more about the 'PRagMatic paediatric trial of balanced vs normal saline fluid in sepsis', a research study involving children with Sepsis.
Purpose
Approximately 2,500 non-newborn children die from septic shock each year in the US and thousands more die worldwide. Despite widespread implementation of resuscitation protocols, contemporary studies still report 2-6% mortality for children with septic shock treated in the paediatric ED.
Crystalloids are the standard resuscitative fluid for septic shock. 0.9% Saline and Balanced Fluids (Plasma-Lyte 148, Ringer’s Lactate, and Hartmann’s Solution) 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. However, 0.9% Saline is used in 80-95% of cases of paediatric septic shock, despite data supporting that Balanced Fluid resuscitation may have superior efficacy and safety.
0.9% Saline contains a supra-physiologic concentration of chloride (1.5X that of plasma) and a strong ion difference (SID) of zero but is isotonic compared to extracellular fluid. Balanced Fluids have less chloride, small amounts of additional electrolytes, and a higher SID due to an anion buffer. The high chloride content and low SID of 0.9% Saline has been associated with acute kidney injury (AKI), acidemia, hyperkalaemia, vascular permeability, inflammation, coagulopathy, fluid overload, and death.
Balanced Fluids have showed a 1-4% absolute mortality reduction and up to a 50% lower odds of dialysis compared to 0.9% Saline in observational and non-randomised interventional studies in adult sepsis. Because definitive conclusions could not be drawn from existing observational and non-randomised studies, 0.9% Saline overwhelmingly remains the most commonly used fluid based on historical precedent (particularly in paediatrics).
In paediatrics, a recent propensity-matched analysis of 2,398 patients found a 2% lower mortality for children receiving Balanced Fluids versus 0.9% Saline. Conversely, in a matched analysis of 4,234 children with septic shock from 382 hospitals in the Premier Healthcare Alliance, there was no superiority of Balanced Fluids over 0.9% Saline.
However, we noted that highly selective use of Balanced Fluids made it impossible to fully eliminate confounding factors and we concluded that these retrospective data are best used to support equipoise rather than declare 0.9% Saline and Balanced Fluids to be of equal benefit. To definitively test the comparative effectiveness of 0.9% Saline versus Balanced Fluids, a well-powered randomised controlled trial (RCT) is necessary.
Information for participants
Get involved
PRoMPT BOLUS will enrol children over 6 months and less than 18 years of age with possible sepsis during an emergency department visit at a study site.
Children will be considered having possible sepsis if their doctor thinks they may have sepsis that will require treatment with both IV antibiotics and IV fluids, and their doctor is worried about possible shock.
The study will include children who are previously healthy, as well as children with chronic medical problems.
Research team
Role | Team member |
---|---|
Lead Researcher & Principal Investigator | A/Prof Elliot Long |
Research Coordinator | Amanda Williams |
Australian and New Zealand Steering Committee | Catherine Wilson Dr Meredith Borland Dr Sarah McNab Dr Ben Gelbart Prof Ed Oakley Prof Franz Babl Prof Stuart Dalziel |
Research
Results of pilot study
The PRoMPT BOLUS Feasibility Pilot Clinical Trial was performed between January and August 2018 at the Children’s Hospital of Philadelphia to determine whether the feasibility of a multi-centre, pragmatic randomised clinical trial to compare balanced and 0.9% saline fluid resuscitation in children with suspected septic shock.
Eligible patients were >6 months to <18 years-old who were treated in the emergency department for suspected septic shock, operationalized as blood culture, antibiotics, and fluid resuscitation for abnormal perfusion. The clinical team carried screening, enrolment, and randomisation out as part of routine care.
Patients were randomised to receive either lactated Ringer’s or 0.9% saline for up to 48 hours following randomisation.
Other than fluid type, all treatment decisions were at the clinical team’s discretion. Feasibility outcomes were:
- proportion of eligible patients enrolled
- acceptability of enrolment via the U.S. federal exception from informed consent (EFIC) regulations, and
- adherence to randomised study fluid administration.
The key findings from this study were:
- A high proportion (85%) of eligible patients were able to be enrolled.
- Families, patients, and caregivers were supportive of enrolment through EFIC, with 43 (98%) of the 44 patients enrolled under EFIC agreeing to complete the study.
- Hospital staff could follow the randomization scheme to achieve strong protocol adherence with patients randomized to lactated Ringer’s receiving a median of only 20% of study fluid as 0.9% saline compared to 99% of study fluid as 0.9% saline in the saline arm (absolute difference 79%, 95% CI 48 to 85%).
These results support it is feasible to use a pragmatic study design to study the comparative effectiveness of balanced versus 0.9% saline fluid resuscitation for paediatric septic shock.
Collaborators
The PROMPT Bolus study is an international randomised controlled trial enrolling participants in Australia, New Zealand, Canada, and the United States of America.
The PROMPT Bolus study is being conducted as a collaboration between the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network, the Pediatric Emergency Care Applied Research Network (PECARN) and the Pediatric Emergency Research Canada (PERC) research network.
Funding
The PROMPT Bolus study is funded through the Medical Research Futures Fund (MRFF) International Clinical Trial Collaborations (ICTC)
Contact us
PRoMPT BOLUS Study
Murdoch Children's Research Institute
The Royal Children's Hospital
50 Flemington Road
Parkville VIC 3052
Australia
Email: [email protected]