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

NCT ID: NCT03080038

Last Updated: 2022-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 406 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-06
• Study Completion Date: 2021-12-31

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.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Fluid Sparing Resuscitation Strategy

Intervention Type: 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.

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 29 Days
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Critical Care Trials Group

OTHER

Sponsor Role: collaborator

Pediatric Emergency Research Canada

UNKNOWN

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Canadian Blood Services

OTHER

Sponsor Role: collaborator

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Melissa Parker

Associate Professor of Pediatrics, McMaster University; Staff Physician, McMaster Children's Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Melissa Parker, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

McMaster Children's Hospital and McMaster University

Locations

Alberta Children's Hospital

Calgary, Alberta, Canada

Stollery Children's Hospital

Edmonton, Alberta, Canada

Winnipeg Children's Hospital

Winnipeg, Manitoba, Canada

McMaster Children's Hospital

Hamilton, Ontario, Canada

Children's Hospital of Western Ontario

London, Ontario, Canada

Sickkids

Toronto, Ontario, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

CHU de Québec-Université Laval

Québec, Quebec, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 27876084 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39072232 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29863640 (View on PubMed)

Related Links

https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-016-1689-2

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

Other Identifiers

0833

Identifier Type: -

Identifier Source: org_study_id