Clinical trial NCT01973907: Pilot Study for the SQUEEZE Trial
Official title: Pilot Study 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Septic Shock
Keywords: Sepsis
Septic Shock
Fluid Therapy
Pediatrics
Resuscitation
Emergency Medicine
Critical Care
Lead sponsor: McMaster Children's Hospital
Sponsor class: OTHER
Collaborators: name: Hamilton Health Sciences Corporation
name: McMaster University
name: Canadian Critical Care Trials Group
First posted: 2013-11-01
Enrollment: 53
Sex: ALL
Minimum age (years): 29
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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: Current pediatric surviving sepsis guidelines from the American College of Critical Care Medicine (ACCM) emphasize an early and goal-directed approach to resuscitation. These guidelines suggest that fluid resuscitation should be aggressive with repeated intravenous (IV) fluid boluses of 20 mL/kg, such that some children may require as much as 200 mL/kg of fluid to achieve therapeutic endpoints. The guidelines also recommend the initiation of vasoactive agents at the stage of "fluid refractory shock", i.e. when there is persistent hypoperfusion despite at least 60 ml/kg IV fluid. Improvements in pediatric septic shock survival have been attributed to adherence to the first iteration of the ACCM septic shock guidelines, and the use of goal directed targets. However, the largest and most publicized pediatric trial of fluid resuscitation in children with suspected septic shock (FEAST Trial), published in NEJM in 2011, demonstrated an increased mortality among children treated with aggressive fluid resuscitation in comparison to the conservative fluid resuscitation arm. As a result, the pediatric critical care community clearly acknowledges that these results, while important, are not necessarily generalizable to developed countries such as Canada.

Emerging publications in the ICU literature suggest that excessive compared to conservative fluid administration in adults with septic shock worsens outcomes such as duration of mechanical ventilation, complications related to the third-spacing of fluids, length of ICU stay, and mortality. A systematic review published in August 2012 reveals a paucity of randomized controlled trial (RCT) evidence apart from the FEAST trial examining the impact of fluid resuscitation on mortality in children with septic shock. This raises the important question of whether children in developed countries would also benefit from a fluid sparing resuscitation strategy to achieve the ACCM goal-directed targets. Use of such a fluid sparing strategy would, by default, require earlier initiation and preferential escalation of vasoactive medications to meet ACCM hemodynamic goals. The optimal degree of fluid resuscitation and the timing of initiation of vasoactive support in order to achieve therapeutic targets in children with septic shock remains unanswered.

This Pilot Randomized Controlled Trial constitutes the first step in answering our research question of whether, in pediatric patients with septic shock, use of a fluid sparing strategy to achieve ACCM therapeutic goals, results in improved clinical outcomes without an increased risk of adverse events, compared to the usual care of aggressive fluid resuscitation as currently recommended by the ACCM guidelines. The purpose of the pilot study is to determine feasibility and inform the appropriate methodological design of the larger multi-centre RCT to fully answer our research question. The hypothesis of the pilot study is that the SQUEEZE Trial is feasible to conduct.

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria for 1 and 3 must be answered YES to be eligible for study.

1. Age 29 days to less than 18 years of age

2a) 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)

2b) Suspected or Confirmed Septic Shock (Shock due to Suspected or Confirmed Infectious Cause)

2c) 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

3. 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

Primary outcomes:
measure: Feasibility of conducting the SQUEEZE Trial
timeFrame: The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment
Secondary outcomes:
measure: Appropriateness of eligibility criteria
timeFrame: The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment
measure: Clinical outcomes
timeFrame: The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment
measure: Process Feasibility
timeFrame: The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment
measure: Resource Feasibility
timeFrame: The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment
measure: Management Feasibility
timeFrame: The earliest of: 1. Recruitment of the planned 50 participants, or 2. 24 months following initiation of recruitment
Other outcomes:
measure: Daily Fluids
timeFrame: Over the Duration of the Intervention Period, Defined as from the time of Randomization (Time zero) until 24 hours after Shock is Reversed
measure: Fluids Received in the 24 hours prior to study entry
timeFrame: 24 hour period immediately prior to randomization (time zero)
measure: Positive Culture results from specimens obtained during the Intervention Period
timeFrame: Over the Duration of the Intervention Period, Defined as from the time of Randomization (Time zero) until 24 hours after Shock is Reversed
measure: Positive Culture Results from specimens obtained in the 24 hours immediately prior to study entry
timeFrame: The 24 hour period immediately prior to Randomization (Time zero)
Locations:
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
Study officials:
affiliation: McMaster University and McMaster Children's Hospital
name: Melissa J Parker, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.