title: A trial to determine whether septic shock-reversal is quicker in pediatric patients randomized to an early goal-directed fluid-sparing strategy versus usual care (SQUEEZE): study protocol for a pilot randomized controlled trial.
abstract: Current pediatric septic shock resuscitation guidelines from the American College of Critical Care Medicine focus on the early and goal-directed administration of intravascular fluid followed by vasoactive medication infusions for persistent and fluid-refractory shock. However, accumulating adult and pediatric data suggest that excessive fluid administration is associated with worse patient outcomes and even increased risk of death. The optimal amount of intravascular fluid required in early pediatric septic shock resuscitation prior to the initiation of vasoactive support remains unanswered.
  
  
  
  The SQUEEZE Pilot Trial is a pragmatic, two-arm, parallel-group, open-label, prospective pilot randomized controlled trial. Participants are children aged 29 days to under 18 years with suspected or confirmed septic shock and a need for ongoing resuscitation. Eligible participants are enrolled under an exception to consent process and randomly assigned via concealed allocation to either the Usual Care (control) or Fluid Sparing (intervention) resuscitation strategy. The primary objective of this pilot trial is to determine feasibility, based on the ability to enroll participants and to adhere to the study protocol. The primary outcome measure by which success will be determined is participant enrollment rate ("pass" defined as at least two participants/site/month, recognizing that enrollment may be slower during the run-in phase). Secondary objectives include assessing (1) appropriateness of eligibility criteria, and (2) completeness of clinical outcomes to inform the endpoints for the planned multisite trial. To support the nested translational study, SQUEEZE-D, we will also evaluate the feasibility of describing cell-free DNA (a procoagulant molecule with prognostic utility) in blood samples obtained from children enrolled into the SQUEEZE Pilot Trial at baseline and at 24 h.
  
  
  
  The optimal degree of fluid resuscitation and the timing of initiation of vasoactive support in order to achieve recommended therapeutic targets in children with septic shock remains unanswered. No prospective study to date has examined this important question for children in developed countries including Canada. Recruitment for the SQUEEZE Pilot Trial opened on 6 January 2014. Findings will inform the feasibility of the planned multicenter trial to answer our overall research question.
  
  
  
  ClinicalTrials.gov Identifier NCT01973907 , registered on 23 October 2013.
authors.affiliation: Division of Pediatric Critical Care, Department of Pediatrics, McMaster Children's Hospital and McMaster University, HSC 3E-20,1280 Main Street West, Hamilton, ON, L8S 4K1, Canada. parkermj@mcmaster.ca.|Department of Clinical Epidemiology and Biostatistics, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada. parkermj@mcmaster.ca.|Division of Emergency Medicine, Department of Pediatrics, the Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. parkermj@mcmaster.ca.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Parker
authors.affiliation: Division of Pediatric Critical Care, Department of Pediatrics, McMaster Children's Hospital and McMaster University, HSC 3E-20,1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.|Department of Clinical Epidemiology and Biostatistics, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.|Department of Anesthesia, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.|Biostatistics Unit,/FSORC, St Joseph's Healthcare Hamilton, 3rd floor Martha Wing, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6, Canada.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.affiliation: Department of Medicine, McMaster University, DBRI, Rm C5-106 and 107, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
authors.forename: Alison
authors.initials: A
authors.lastname: Fox-Robichaud
authors.affiliation: Department of Medicine, McMaster University, DBRI, Rm C5-106 and 107, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Liaw
authors.affiliation: Division of Pediatric Critical Care, Department of Pediatrics, McMaster Children's Hospital and McMaster University, HSC 3E-20,1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.|Department of Clinical Epidemiology and Biostatistics, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Choong
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects / Q000379:methods*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009864:Ontario; D010865:Pilot Projects; D011446:Prospective Studies; D020127:Recovery of Function; D012107:Research Design; D012151:Resuscitation / Q000009:adverse effects / Q000379:methods*; D012772:Shock, Septic / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014662:Vasoconstrictor Agents
keywords: Fluid therapy; Pediatrics; Resuscitation; Sepsis; Shock