SQUEEZE Trial: A Trial to Determine Whether Septic Shock Reversal is Quicker in Pediatric Patients Randomized to an Early Goal Directed Fluid Sparing Strategy vs. Usual Care (SQUEEZE)

The purpose of the SQUEEZE Trial is to determine which fluid resuscitation strategy results in the best outcomes for children treated for suspected or confirmed septic shock. In this study, eligible children will be randomized to either the 'Usual Care Arm' or the 'Fluid Sparing Arm'. Children will receive treatment according to current ACCM Septic Shock Resuscitation Guidelines, with the assigned resuscitation strategy used to guide administration of further fluid boluses as well as the timing of initiation and escalation of vasoactive medications to achieve ACCM recommended hemodynamic targets.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Other: Fluid Sparing Resuscitation Strategy

Detailed Description

Please see published pilot trial protocol for more information about the SQUEEZE Trial and rationale for this study.

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 2C8
      • Stollery Children's Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1S9
      • Winnipeg Children'S Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster Children's Hospital
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital of Western Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • SickKids
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
    • Québec City, Quebec, Canada, G1V 4G2
      • CHU de Quebec-Universite Laval

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Inclusion Criteria for 1 and 3 must be answered YES to be eligible for study.

• Age 29 days to less than 18 years of age

• Patient has Persistent Signs of Shock including one or more of the following:

  • Vasoactive Medication Dependence
  • Hypotension (Systolic Blood Pressure and/or Mean Blood Pressure less than the 5th percentile for age)
  • Abnormal Perfusion (2 or more of: abnormal capillary refill, tachycardia, decreased level of consciousness, decreased urine output)
• Suspected or Confirmed Septic Shock (Shock due to Suspected or Confirmed Infectious Cause)
• Patient has received initial fluid resuscitation of: Minimum of 40 mL/kg of isotonic crystalloid (0.9% Normal Saline and/or Ringer's Lactate) and/or colloid (5% albumin) as fluid boluses within the previous 6 hours for patients weighing less than 50 kg, OR Minimum of 2 litres (2000 mL) of isotonic crystalloid (0.9% Normal Saline and/or Ringer's Lactate) and/or colloid (5% albumin) as fluid boluses within the previous 6 hours for patients weighing 50 kg or more.
• Patient has Fluid Refractory Septic Shock as defined by the Presence of all of 2a, 2b, and 2c.

Exclusion Criteria:

• Patient admitted to the Neonatal Intensive Care Unit (NICU)
• Patient requiring resuscitation in the Operating Room (OR) or Post-Anesthetic Care Unit (PACU)
• Full active resuscitative treatment not within the goals of care
• Shock Secondary to Cause other than Sepsis (i.e. obvious signs of cardiogenic shock, anaphylactic shock, hemorrhagic shock, spinal shock)
• Previous enrolment in this trial, where known by the research team

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual Care Resuscitation Strategy; Decisions regarding the IV/IO administration of isotonic fluid boluses and/or the initiation and escalation of vasoactive medication infusions are left to the discretion of the treating physician and medical team. We ask that vasoactive medications not be initiated until at least 60 mL/kg (3 litres for children ≥ 50 kg) of isotonic fluid bolus therapy has been administered. The treating physician and medical team are advised to follow ACCM guidelines for the resuscitation of neonatal and pediatric septic shock and to target ACCM recommended therapeutic endpoints.
Experimental: Fluid Sparing Resuscitation Strategy; The treating physician and medical team are advised to follow the assigned Fluid Sparing Resuscitation Strategy to guide decisions regarding the IV/IO administration of further isotonic fluid boluses, and the timing of initiation and escalation of vasoactive medication infusions to target the therapeutic endpoints recommended in the ACCM guidelines for the resuscitation of neonatal and pediatric septic shock.	Other: Fluid Sparing Resuscitation Strategy; Tier 1: Initiate IV/IO vasoactive medication infusion support immediately. Further IV/IO isotonic fluid bolus therapy [crystalloid (0.9% Normal Saline or Ringers Lactate) or colloid (5% Albumin)] should be avoided; small volume isotonic fluid boluses [5-10 mL/kg (250-500 mL for participants ≥ 50 kg)] may be provided if required due to A. Clinically unacceptable delay in ability to initiate vasoactive medication infusion(s) and/or 2. Documented intravascular hypovolemia. Tier 2: Vasoactive medication(s) should be preferentially titrated/escalated to achieve recommended ACCM hemodynamic goals. Further IV/IO isotonic fluid bolus therapy [crystalloid (0.9% Normal Saline or Ringers Lactate) or colloid (5% Albumin)] should be avoided; small volume isotonic fluid boluses [5-10 mL/kg (250-500 mL for participants ≥ 50 kg)] may be provided if required due to A. Documented intravascular hypovolemia. Intervention end: Patient is free from vasoactive medication support and shock is reversed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in time to shock reversal	Difference (in hours) in time to shock reversal between the two study groups. Not available where death occurs while still in shock, or if the patient is placed on mechanical circulatory support for refractory shock.	This outcome can be ascertained typically within 14 days of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures of Organ Dysfunction - Pediatric logistic organ dysfunction score	Pediatric logistic organ dysfunction score	28 days
Measures of Organ Dysfunction - Acute Kidney Injury	Acute Kidney Injury	28 days
Measures of Organ Dysfunction - Ventilator Free Days	Ventilator Free Days	28 days
Complications possibly attributable to fluid overload or third spacing of fluids - Soft tissue edema	Soft tissue edema	Intervention Period (from randomization until shock is reversed; typically within 14 days)
Complications possibly attributable to fluid overload or third spacing of fluids - Pulmonary edema	Pulmonary edema	Intervention Period (from randomization until shock is reversed; typically within 14 days)
Complications possibly attributable to fluid overload or third spacing of fluids - Pleural effusion requiring drainage	Pleural effusion requiring drainage	Intervention Period (from randomization until shock is reversed; typically within 14 days)
Complications possibly attributable to fluid overload or third spacing of fluids - Abdominal Compartment Syndrome	Abdominal Compartment Syndrome	Intervention Period (from randomization until shock is reversed; typically within 14 days)
Complications possibly attributable to fluid overload or third spacing of fluids - Diuretic Exposure	Diuretic Exposure	From randomization until 7 days after shock is reversed
Complications possibly attributable to inotrope/vasopressor use - Clinical signs of digital tissue schema	Clinical signs of digital tissue schema	Intervention Period (from randomization until shock is reversed; typically within 14 days)
Complications possibly attributable to inotrope/vasopressor use - Digital ischemia requiring revision amputation	Digital ischemia requiring revision amputation	90 days
Complications possibly attributable to inotrope/vasopressor use - Clinical signs of compromised bowel perfusion	Clinical signs of compromised bowel perfusion	From randomization until 7 days after shock is reversed
Critical Care Treatments as binary measurement yes/no	Critical care treatments performed during intervention period.	Intervention Period (from randomization until shock is reversed; typically within 14 days)
Paediatric Intensive Care Unit Length of Stay	Paediatric Intensive Care Unit Length of Stay	Up to 90 days
Hospital Length of Stay	Hospital Length of Stay	Up to 90 days
Mortality Measures	Death	28-, 90- day, hospital mortality
Health Service Outcomes - Paediatric Intensive Care Unit Admission Rate	Paediatric Intensive Care Unit Admission Rate	28 days

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR); Hamilton Health Sciences Corporation; Canadian Blood Services; Canadian Critical Care Trials Group; Pediatric Emergency Research Canada
• Investigators: Principal Investigator: Melissa Parker, MD, MSc, McMaster Children's Hospital and McMaster University

Publications and helpful links

General Publications

• Parker MJ, Thabane L, Fox-Robichaud A, Liaw P, Choong K; Canadian Critical Care Trials Group and the Canadian Critical Care Translational Biology Group. 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. Trials. 2016 Nov 22;17(1):556. doi: 10.1186/s13063-016-1689-2.
• Parker MJ. What Goes Up, Must Go Down? Pediatr Crit Care Med. 2018 Jun;19(6):579-581. doi: 10.1097/PCC.0000000000001543. No abstract available.

Helpful Links

• 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

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2017
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: March 14, 2017
• First Posted (Actual): March 15, 2017

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Shock; Emergency Medicine; Pediatrics; Septic Shock; Sepsis; Critical Care; Resuscitation; Fluid Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: 0833

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The final trial data set will be made public.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No