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

McMaster University406 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

406

Conditions

Septic Shock

Interventions

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.

Eligibility

Sex: ALLMin age: 29 DaysMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (8)

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

Outcomes

Primary Outcomes

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.

Time frame: This outcome can be ascertained typically within 14 days of randomization

Secondary Outcomes

Measures of Organ Dysfunction - Pediatric logistic organ dysfunction score

Pediatric logistic organ dysfunction score

Time frame: 28 days

Measures of Organ Dysfunction - Acute Kidney Injury

Acute Kidney Injury

Time frame: 28 days

Measures of Organ Dysfunction - Ventilator Free Days

Ventilator Free Days

Time frame: 28 days

Complications possibly attributable to fluid overload or third spacing of fluids - Soft tissue edema

Soft tissue edema

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 90 days

Complications possibly attributable to inotrope/vasopressor use - Clinical signs of compromised bowel perfusion

Clinical signs of compromised bowel perfusion

Time frame: From randomization until 7 days after shock is reversed

Critical Care Treatments as binary measurement yes/no

Critical care treatments performed during intervention period.

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

Paediatric Intensive Care Unit Length of Stay

Time frame: Up to 90 days

Hospital Length of Stay

Time frame: Up to 90 days

Mortality Measures

Death

Time frame: 28-, 90- day, hospital mortality

Health Service Outcomes - Paediatric Intensive Care Unit Admission Rate

Paediatric Intensive Care Unit Admission Rate

Time frame: 28 days