Pilot Study for the SQUEEZE Trial

NCT01973907 | Completed Phase 3

• 1 other identifier: 13-295
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Septic Shock

Keywords

Sepsis; Septic Shock; Fluid Therapy; Pediatrics; Resuscitation; Emergency Medicine; Critical Care

Outcome Measures

Primary Outcomes (1)

• Feasibility of conducting the SQUEEZE Trial

  The Primary Outcome of Feasibility of conducting the SQUEEZE Trial will be evaluated based on the following: 1. Participant enrolment rate: We will define success as an enrolment rate of at least 2 patients/month (recognizing that enrolment may be slower during the study run-in phase). 2. Protocol adherence: the ability to execute the study procedures. We will assess our ability to initiate study procedures in enrolled patients within 1 hour of randomization.

  The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment

Secondary Outcomes (5)

• Appropriateness of eligibility criteria

  The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment

• Clinical outcomes

  The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment

• Process Feasibility

  The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment

• Resource Feasibility

  The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment

• Management Feasibility

  The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment

Other Outcomes (4)

• Daily Fluids

  Over the Duration of the Intervention Period, Defined as from the time of Randomization (Time zero) until 24 hours after Shock is Reversed

• Fluids Received in the 24 hours prior to study entry

  24 hour period immediately prior to randomization (time zero)

• Positive Culture results from specimens obtained during the Intervention Period

  Over the Duration of the Intervention Period, Defined as from the time of Randomization (Time zero) until 24 hours after Shock is Reversed

Study Arms (2)

Usual Care Resuscitation Strategy

NO INTERVENTION

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.

Fluid Sparing Resuscitation Strategy

EXPERIMENTAL

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

Interventions

Fluid Sparing Resuscitation Strategy OTHER

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.

Fluid Sparing Resuscitation Strategy

Eligibility Criteria

• Age: 29 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \. Age 29 days to less than 18 years of age
• a) Patient has Persistent Signs of Shock including one or more of the following: i) Vasoactive Medication Dependence ii) Hypotension (Systolic Blood Pressure and/or Mean Blood Pressure less than the 5th percentile for age) iii) Abnormal Perfusion (2 or more of: abnormal capillary refill, tachycardia, decreased level of consciousness, decreased urine output)
• b) Suspected or Confirmed Septic Shock (Shock due to Suspected or Confirmed Infectious Cause)
• c) 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster Children's Hospital: lead
• Hamilton Health Sciences Corporation: collaborator
• McMaster University: collaborator
• Canadian Critical Care Trials Group: collaborator

Study Sites (1)

McMaster Children's Hospital

Hamilton, Ontario, L8S 4K1, Canada

Location

Related Publications (3)

• Parker MJ, Choong K, Fox-Robichaud A, Liaw PC, Thabane L; Canadian Critical Care Trials Group and the Canadian Critical Care Translational Biology Group. The SQUEEZE pilot 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. Pilot Feasibility Stud. 2025 Nov 28;11(1):153. doi: 10.1186/s40814-025-01731-4.

  PMID: 41316443 DERIVED

• Parker MJ, Foster G, Fox-Robichaud A, Choong K, Mbuagbaw L, Thabane L; With the SQUEEZE Trial Steering Committee and on behalf of the SQUEEZE Trial Investigators, the Canadian Critical Care Trials Group, Pediatric Emergency Research Canada, and the Canadian Critical Care Translational Biology Group. Statistical analysis plan for the 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). Crit Care Resusc. 2024 Jun 22;26(2):123-134. doi: 10.1016/j.ccrj.2024.02.002. eCollection 2024 Jun.

  PMID: 39072232 DERIVED

• 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.

  PMID: 27876084 DERIVED

MeSH Terms

Conditions

Shock, Septic; Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Melissa J Parker, MD, MSc

  McMaster University and McMaster Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics, McMaster University; Staff Physician, McMaster Children's Hospital

Study Record Dates

• First Submitted: October 27, 2013
• First Posted: November 1, 2013
• Study Start: January 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: August 18, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)