Mechanistic Assessment of Norepinephrine TheRapy vs. Angiotensin-II in Septic Shock (MANTRA) Grant Submission- Dysfunctional Renin-Angiotensin System in Septic Shock
Wake Forest University Health Sciences
Summary
Despite best therapy efforts, sepsis and septic shock are associated with mortality rates of up to 40%. This clinical trial will determine the benefit of exogenous Angiotensin II versus norepinephrine (conventional care) treatment in septic shock patients. This trial will determine whether there are better predictors of septic shock severity. This approach may inform more appropriate treatment regimens and improve outcomes for these patients.
Description
This study will determine whether normalization of renin-angiotensin-aldosterone system (RAAS) signaling in sepsis occurs more rapidly with treatment with Angiotensin II compared with conventional vasopressors. Trial samples will be used to identify the best RAAS biomarker predictor of treatment response via in-depth longitudinal analysis of RAAS component and to determine the extent and mechanisms of Angiotensin II impact on innate immune function during sepsis. Successful accomplishment of our aims will provide the capability to improve endotyping of septic patients by establishing the most…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: \- The presence of septic shock, defined by sepsis-3 criteria: 1-adult patients (18 years or older) with septic shock, defined by SEPSIS-3 criteria: a) suspected or known infection, b) hypotension requiring vasopressors, and c) lactate \>2mmol/L 2-receiving either norepinephrine or phenylephrine with or without additional vasopressor support 3- total norepinephrine equivalent dose (NED) ≥0.1 mcg/kg/min and ≤0.5 mcg/kg/min, to maintain a MAP of at least 65 mmHg, is required for randomization 4-ability to consent and randomize within 24 hrs of first reaching NED threshold an…
Interventions
- DrugAngiotensin II
randomized to receive Angiotensin II continuous infusion for up to 48 hours
- DrugNorepinephrine
randomized to receive Norepinephrine continuous infusion for up to 48 hours
Locations (2)
- Massachusetts General Hospital-HarvardBoston, Massachusetts
- Atrium Health Wake Forest BaptistWinston-Salem, North Carolina