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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

View Article: PubMed Central - PubMed

ABSTRACT

Background: Current pediatric septic shock resuscitation guidelines from the American College of Critical Care Medicine focus on the early and goal-directed administration of intravascular fluid followed by vasoactive medication infusions for persistent and fluid-refractory shock. However, accumulating adult and pediatric data suggest that excessive fluid administration is associated with worse patient outcomes and even increased risk of death. The optimal amount of intravascular fluid required in early pediatric septic shock resuscitation prior to the initiation of vasoactive support remains unanswered.

Methods/design: The SQUEEZE Pilot Trial is a pragmatic, two-arm, parallel-group, open-label, prospective pilot randomized controlled trial. Participants are children aged 29 days to under 18 years with suspected or confirmed septic shock and a need for ongoing resuscitation. Eligible participants are enrolled under an exception to consent process and randomly assigned via concealed allocation to either the Usual Care (control) or Fluid Sparing (intervention) resuscitation strategy. The primary objective of this pilot trial is to determine feasibility, based on the ability to enroll participants and to adhere to the study protocol. The primary outcome measure by which success will be determined is participant enrollment rate ("pass" defined as at least two participants/site/month, recognizing that enrollment may be slower during the run-in phase). Secondary objectives include assessing (1) appropriateness of eligibility criteria, and (2) completeness of clinical outcomes to inform the endpoints for the planned multisite trial. To support the nested translational study, SQUEEZE-D, we will also evaluate the feasibility of describing cell-free DNA (a procoagulant molecule with prognostic utility) in blood samples obtained from children enrolled into the SQUEEZE Pilot Trial at baseline and at 24 h.

Discussion: The optimal degree of fluid resuscitation and the timing of initiation of vasoactive support in order to achieve recommended therapeutic targets in children with septic shock remains unanswered. No prospective study to date has examined this important question for children in developed countries including Canada. Recruitment for the SQUEEZE Pilot Trial opened on 6 January 2014. Findings will inform the feasibility of the planned multicenter trial to answer our overall research question.

Trial registration: ClinicalTrials.gov Identifier NCT01973907, registered on 23 October 2013.

Electronic supplementary material: The online version of this article (doi:10.1186/s13063-016-1689-2) contains supplementary material, which is available to authorized users.

No MeSH data available.


Flow of participants
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Fig1: Flow of participants

Mentions: The detailed pilot trial protocol is organized in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines, with items corresponding to the SPIRIT 2013 checklist (Additional file 1) [37, 38]. Required items, such as the World Health Organization Trial Registration Data Set (Additional file 2), a schedule of enrollment, interventions, and assessments (Additional file 3), and a participant flow diagram (Fig. 1) are included here. The protocol was registered at ClinicalTrials.gov (NCT01973907) prior to enrollment of the first participant.Fig. 1


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
Flow of participants
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5120449&req=5

Fig1: Flow of participants
Mentions: The detailed pilot trial protocol is organized in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines, with items corresponding to the SPIRIT 2013 checklist (Additional file 1) [37, 38]. Required items, such as the World Health Organization Trial Registration Data Set (Additional file 2), a schedule of enrollment, interventions, and assessments (Additional file 3), and a participant flow diagram (Fig. 1) are included here. The protocol was registered at ClinicalTrials.gov (NCT01973907) prior to enrollment of the first participant.Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Current pediatric septic shock resuscitation guidelines from the American College of Critical Care Medicine focus on the early and goal-directed administration of intravascular fluid followed by vasoactive medication infusions for persistent and fluid-refractory shock. However, accumulating adult and pediatric data suggest that excessive fluid administration is associated with worse patient outcomes and even increased risk of death. The optimal amount of intravascular fluid required in early pediatric septic shock resuscitation prior to the initiation of vasoactive support remains unanswered.

Methods/design: The SQUEEZE Pilot Trial is a pragmatic, two-arm, parallel-group, open-label, prospective pilot randomized controlled trial. Participants are children aged 29 days to under 18 years with suspected or confirmed septic shock and a need for ongoing resuscitation. Eligible participants are enrolled under an exception to consent process and randomly assigned via concealed allocation to either the Usual Care (control) or Fluid Sparing (intervention) resuscitation strategy. The primary objective of this pilot trial is to determine feasibility, based on the ability to enroll participants and to adhere to the study protocol. The primary outcome measure by which success will be determined is participant enrollment rate ("pass" defined as at least two participants/site/month, recognizing that enrollment may be slower during the run-in phase). Secondary objectives include assessing (1) appropriateness of eligibility criteria, and (2) completeness of clinical outcomes to inform the endpoints for the planned multisite trial. To support the nested translational study, SQUEEZE-D, we will also evaluate the feasibility of describing cell-free DNA (a procoagulant molecule with prognostic utility) in blood samples obtained from children enrolled into the SQUEEZE Pilot Trial at baseline and at 24 h.

Discussion: The optimal degree of fluid resuscitation and the timing of initiation of vasoactive support in order to achieve recommended therapeutic targets in children with septic shock remains unanswered. No prospective study to date has examined this important question for children in developed countries including Canada. Recruitment for the SQUEEZE Pilot Trial opened on 6 January 2014. Findings will inform the feasibility of the planned multicenter trial to answer our overall research question.

Trial registration: ClinicalTrials.gov Identifier NCT01973907, registered on 23 October 2013.

Electronic supplementary material: The online version of this article (doi:10.1186/s13063-016-1689-2) contains supplementary material, which is available to authorized users.

No MeSH data available.