Objective: The overall objective of our research is to determine in children with septic shock whether use of a fluid-sparing strategy results in improved clinical outcomes without an increased risk of adverse events compared to usual care. The specific objective of this pilot randomized controlled trial was to evaluate the feasibility of a definitive multicenter trial to answer our research question. Design: Pragmatic, 2-arm, parallel group, open label, prospective pilot randomized controlled trial including a nested biosample-based translational study. Setting: Pediatric tertiary care centre Patients: Children aged 29 days to <18 years of age presenting to the Emergency Department or admitted to an in-patient ward (including the PICU) with suspected or confirmed septic shock and a need for ongoing resuscitation. Interventions: Fluid-sparing vs. usual care resuscitation strategy continued until shock reversal. The fluid-sparing intervention comprised instructions to restrict fluid bolus therapy in conjunction with early initiation and/or preferential use of vasoactive medication support as a strategy to spare fluid while targeting the hemodynamic goals specified in the American College of Critical Care Medicine Surviving Sepsis Guidelines. The usual care strategy did not limit use of fluid bolus therapy. Measurements and Main Results: 53 were randomized to usual care (n=27) or fluid-sparing (n=26). Fifty-one participants were available for primary outcome analysis. Primary feasibility outcomes related to participant enrolment and protocol adherence. Enrolment rate was 1.8 (51/29); 95% confidence interval [CI]: 1.3-2.3 participants/month. Study procedures were implemented in 49/51 (96.1%), 95% CI: 86.5-99.5% participants within 1 hour of randomization in a median (quartile range [IQR]) of 8 (5, 15) minutes. The protocol required use of an exception to consent process and consent for ongoing participation was 48/51 (94.1%), 95% CI: 83.8-98.8%. There were no serious adverse events. Conclusions: We concluded the large multicenter SQUEEZE Trial feasible to conduct. Trial Registration: ClinicalTrials.gov [NCT01973907]

The authors have declared no competing interest.

ClinicalTrials.gov ID: NCT01973907

https://doi.org/10.1186/s13063-016-1689-2

i) Hamilton Health Sciences New Investigator Fund 2013-2015 (PI: Parker MJ. Funding reference number: NIF 12307; Operating Grant: $50,000) ii) Hamilton Health Sciences Research Early Career Award 2013, 2014 (PI: Parker MJ. Award - Programmatic Support: $100,000) iii) Hamilton Health Sciences Research Strategic Initiatives 2013-2016 (PI: Fox-Robichaud A. Funding reference number: RFA-2013 Fox-Robichaud; Operating Grant: $299,453) Funding support for several translational studies, including SQUEEZE-D. iv) Canadian Blood Services/Canadian Institutes of Health Research New Investigator Salary Award 2014-2019 (PI: Parker MJ. Funding reference number: CIHRPA201309-MP-322414; Award: $300,000) Supports protected research time for MJP to dedicate to this program of research. v) Canadian Child Health Clinician Scientist Program Career Enhancement Program Award 2015-2019 (PI: Parker MJ. Award - Programmatic Support: $25,000). The authors and their institutions did not receive payment or services from a third party for any aspect of the submitted work.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Hamilton Integrated Research Ethics Board (HIREB) of McMaster University, St. Joseph's Healthcare Hamilton, and Hamilton Health Sciences (which includes McMaster Children's Hospital) gave ethical approval for this work. (Project ID: 13-295)

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.