Stroke volUme-baSed fluid resusciTAtIoN in AP (SUSTAIN)

University Of Southern California, Los Angeles CA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT: Acute Pancreatitis (AP) is a leading gastrointestinal cause of gastrointestinal hospitalization in the United States with substantial mortality (>5000 deaths), rising incidence (>3% annually), and high cost of 5 billion $US annually. Nevertheless, there are no FDA approved treatments for AP. Recent National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) workshops (i.e. July 26, 2023) underscore the critical need for therapeutic interventions for acute pancreatitis. Fluid therapy (FT) is currently recognized as the primary treatment in AP, but the optimal strategy for administration is unknown. We propose the multi-center randomized controlled SUSTAIN (Stroke volUme-baSed fluid resuscitation) which will address this knowledge gap in AP. In the WATERFALL (Early Weight-Based Aggressive vs. ModeraTE Goal-DiRected Fluid ResuscitAtion) randomized controlled trial we challenged the longstanding treatment paradigm that aggressive hydration improves AP outcomes, instead showing that it increases the risk of fluid overload without improving the clinical course. Recently, our team demonstrated that an objective physiologic test, change in stroke volume with passive leg raise, can be used to accurately identify the need for additional resuscitation in AP. Moreover, it is now recognized that, parallel to sepsis, the fluid requirements of AP evolve over sequential stages (i.e. rescue, optimization, stabilization, and de-escalation). Aim 1 of this project compares individualized non-invasive delta stroke-volume guided fluid therapy (DSG-FT)) approach to resuscitation to moderate weight-guided fluid therapy (MWG-FT) of the WATERFALL trial on outcomes in predicted severe AP. This will represent a first randomized trial in AP patients of fluid therapy guided by patient-centric and objective physiologic strategy versus generic weight-based approaches. Aim 2 evaluates a phase-based paradigm to resuscitation in AP. We will derive diagnostic criteria of the AP fluid therapy (FT) phases using the modified Delphi process which we will validate using data from the SUSTAIN trial. We will compare adverse events of FT through the 4 phases of resuscitation in the two arms of the trial The SUSTAIN team is made up of two academic clinical centers with a proven track-record of enrolling diverse populations in AP therapeutic trials. Both are members of Molecular Signatures and Clinical Outcomes in AP (MOSAIC) Study and the NIDDK Type 1 Diabetes in Acute Pancreatitis (T1DAPC) Consortium. Completion of the SUSTAIN study will result in substantial impact which will include 1) a validation of a quantitative and non-invasive approach to provide fluid therapy based on objective parameters compared to the current weight-based approaches which do not consider the real-time physiologic status of patients, 2) define a new paradigm of treatment based on phase of acute pancreatitis based on quantitative parameters, 3) provide a reproducible, objective pathway for clinicians to use in AP treatment.