Renin and Renal Biomarker Response to Angiotensin II

Alexander Flannery30 enrolled

Overview

Septic shock continues to exert a large economic burden around the world. Several developments have occurred that lead to the current study. First, angiotensin II is the newest FDA approved vasopressor agent indicated for use in vasodilatory shock. Several subgroups from the approval trial have indicated that angiotensin II may confer a survival benefit in certain conditions, including those patients requiring continuous renal replacement therapy, those with altered angiotensin I: angiotensin II ratios, and most recently, those with elevated renin levels (which may serve as a surrogate for dysfunctional angiotensin 1: angiotensin II ratios). This open-label, sequential period pilot study will evaluate angiotensin II and biomarker response (renin) in the treatment of septic shock.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Septic Shock Acute Kidney Injury

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Medical ICU admission * Septic shock * Norepinephrine requirement = 0.15 mcg/kg/min for = 30 minutes (if cirrhosis, norepinephrine requirement = 0.1 mcg/kg/min for = 30 minutes) * Kidney Disease Improving Global Outcomes stage 1 or greater Acute Kidney Injury Exclusion Criteria: * Prisoner * Pregnancy * Acute occlusive coronary syndrome requiring intervention or acute myocardial infarction of any degree * Purely cardiogenic shock (no distributive component) * Mesenteric ischemia * Acute ischemic stroke * Hemorrhagic shock * Active treatment of hepatorenal syndrome targeting a Mean Arterial Pressure = 65 mm Hg * Planned withdrawal of care within next 24 hours or no escalation of care * Patient enrolled in an interventional study * High likelihood of medical futility in using this drug: * 3 or more vasopressors required to sustain MAP * Sustained norepinephrine equivalents \> 0.5 mcg/kg/min * COVID-19 positive, or high suspicion of COVID-19

Outcomes

Primary Outcomes

Change in Plasma Renin Levels

Plasma renin levels will be measured from blood collected at baseline, 24 hours, and at shock resolution. Additionally, a 3-hour measurement will be included in the angiotensin II arm.

Time frame: Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)

Secondary Outcomes

Change in Plasma Cystatin C

Cystatin C will be measured from blood collected at baseline, 24 hours, and at shock resolution.

Time frame: Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)

Days to Discontinuation of Catecholamines

Days from enrollment to discontinuation of catecholamines

Time frame: Until shock resolution, up to 14 days

ICU Length of Stay

Number of days in the intensive care unit (ICU).

Time frame: From enrollment to ICU discharge, up to 28 days following enrollment

Number of Participants With In-hospital Mortality

Assessment of all-cause mortality within hospital admission

Time frame: Up to 3 months following enrollment

Renal Replacement Therapy-free Days

Days free of renal replacement therapy from enrollment up to day 28

Time frame: Within 28 days of enrollment

Number of Participants Experiencing Prespecified Safety Outcomes

Incidence of venous thromboembolism, arrhythmia, extremity hypoperfusion, delirium, new ischemic event, new infection

Time frame: Up to 72 hours following shock resolution, no longer than 17 days from enrollment

Change in Plasma Neutrophil Gelatinase-associated Lipocalin (NGAL)

NGAL will be measured from blood collected at baseline, 24 hours, and at shock resolution.

Time frame: Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)

Renin and Renal Biomarker Response to Angiotensin II

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes