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

Official Title
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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

Conditions
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Septic Shock

Intervention / Treatment
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* Other: Fluid Sparing Resuscitation Strategy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 29 Days
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual Care Resuscitation Strategy<br>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<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Shock, Septic Shock, Fluid Therapy, Resuscitation, Pediatrics, Emergency Medicine, Critical Care