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

NCT03080038 | Completed DMC

• 1 other identifier: 0833
• Study Type: interventional
• Target: 406
• Locations: 1 country
• Sites: 8

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Measures of Organ Dysfunction - Pediatric logistic organ dysfunction score

  28 days

• Measures of Organ Dysfunction - Acute Kidney Injury

  28 days

• Measures of Organ Dysfunction - Ventilator Free Days

  28 days

• Complications possibly attributable to fluid overload or third spacing of fluids - 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

  Intervention Period (from randomization until shock is reversed; typically within 14 days)

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
• 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.

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 University: lead
• Canadian Critical Care Trials Group: collaborator
• Pediatric Emergency Research Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Canadian Blood Services: collaborator
• Hamilton Health Sciences Corporation: collaborator

Study Sites (8)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2C8, Canada

Location

Winnipeg Children's Hospital

Winnipeg, Manitoba, R3A 1S9, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8S 4K1, Canada

Location

Children's Hospital of Western Ontario

London, Ontario, N6A 5W9, Canada

Location

Sickkids

Toronto, Ontario, M5G 1X8, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

CHU de Québec-Université Laval

Québec, Quebec, G1V 4G2, Canada

Location

Related Publications (3)

• 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 BACKGROUND

• 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. What Goes Up, Must Go Down? Pediatr Crit Care Med. 2018 Jun;19(6):579-581. doi: 10.1097/PCC.0000000000001543. No abstract available.

  PMID: 29863640 DERIVED

Related 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

MeSH Terms

Conditions

Shock, Septic; Sepsis; Shock

Condition Hierarchy (Ancestors)

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

Study Officials

• Melissa Parker, MD, MSc

  McMaster Children's Hospital and McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• 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: February 28, 2017
• First Posted: March 15, 2017
• Study Start: March 6, 2017
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: May 9, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

CA (8)