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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)

Primary Purpose

Septic Shock

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Fluid Sparing Resuscitation Strategy
Sponsored by
McMaster University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring Sepsis, Shock, Septic Shock, Fluid Therapy, Resuscitation, Pediatrics, Emergency Medicine, Critical Care

Eligibility Criteria

29 Days - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Alberta Children's Hospital
  • Stollery Children's Hospital
  • Winnipeg Children's Hospital
  • McMaster Children's Hospital
  • Children's Hospital of Western Ontario
  • Sickkids
  • CHU Sainte-Justine
  • CHU de Québec-Université Laval

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Usual Care Resuscitation Strategy

Fluid Sparing Resuscitation Strategy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Measures of Organ Dysfunction - Pediatric logistic organ dysfunction score
Pediatric logistic organ dysfunction score
Measures of Organ Dysfunction - Acute Kidney Injury
Acute Kidney Injury
Measures of Organ Dysfunction - Ventilator Free Days
Ventilator Free Days
Complications possibly attributable to fluid overload or third spacing of fluids - Soft tissue edema
Soft tissue edema
Complications possibly attributable to fluid overload or third spacing of fluids - Pulmonary edema
Pulmonary edema
Complications possibly attributable to fluid overload or third spacing of fluids - Pleural effusion requiring drainage
Pleural effusion requiring drainage
Complications possibly attributable to fluid overload or third spacing of fluids - Abdominal Compartment Syndrome
Abdominal Compartment Syndrome
Complications possibly attributable to fluid overload or third spacing of fluids - Diuretic Exposure
Diuretic Exposure
Complications possibly attributable to inotrope/vasopressor use - Clinical signs of digital tissue schema
Clinical signs of digital tissue schema
Complications possibly attributable to inotrope/vasopressor use - Digital ischemia requiring revision amputation
Digital ischemia requiring revision amputation
Complications possibly attributable to inotrope/vasopressor use - Clinical signs of compromised bowel perfusion
Clinical signs of compromised bowel perfusion
Critical Care Treatments as binary measurement yes/no
Critical care treatments performed during intervention period.
Paediatric Intensive Care Unit Length of Stay
Paediatric Intensive Care Unit Length of Stay
Hospital Length of Stay
Hospital Length of Stay
Mortality Measures
Death
Health Service Outcomes - Paediatric Intensive Care Unit Admission Rate
Paediatric Intensive Care Unit Admission Rate

Full Information

First Posted
February 28, 2017
Last Updated
May 6, 2022
Sponsor
McMaster University
Collaborators
Canadian Critical Care Trials Group, Pediatric Emergency Research Canada, Canadian Institutes of Health Research (CIHR), Canadian Blood Services, Hamilton Health Sciences Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT03080038
Brief Title
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
Acronym
SQUEEZE
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
March 6, 2017 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McMaster University
Collaborators
Canadian Critical Care Trials Group, Pediatric Emergency Research Canada, Canadian Institutes of Health Research (CIHR), Canadian Blood Services, Hamilton Health Sciences Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock
Keywords
Sepsis, Shock, Septic Shock, Fluid Therapy, Resuscitation, Pediatrics, Emergency Medicine, Critical Care

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
406 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
29 Days
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melissa Parker, MD, MSc
Organizational Affiliation
McMaster Children's Hospital and McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Facility Name
Stollery Children's Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2C8
Country
Canada
Facility Name
Winnipeg Children's Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1S9
Country
Canada
Facility Name
McMaster Children's Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4K1
Country
Canada
Facility Name
Children's Hospital of Western Ontario
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
Sickkids
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
CHU Sainte-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
CHU de Québec-Université Laval
City
Québec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The final trial data set will be made public.
Citations:
PubMed Identifier
27876084
Citation
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.
Results Reference
background
PubMed Identifier
29863640
Citation
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.
Results Reference
derived
Links:
URL
https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-016-1689-2
Description
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

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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

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