Renin and Renal Biomarker Response to Angiotensin II

Acute Kidney Injury Clinical Trial

Official title:

Renin and Renal Biomarker Response to Angiotensin II Versus Controls in Septic Shock: An Open-Label Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04558359
• Other study ID #: 57411
• Status: Completed
• Phase: Phase 4
• Start date: October 19, 2020
• Est. completion date: July 30, 2023

Study information

• Verified date: August 2023
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 30, 2023
• Est. primary completion date: July 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 AKI

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 MAP = 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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Septic Shock
• Shock, Septic

Intervention

Other:
• Standard of Care
These patients will receive standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured.

Drug:
• Angiotensin II
These patients will receive angiotensin II in addition to standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured.

Locations

Country	Name	City	State
United States	University of Kentucky HealthCare Chandler Medical Center	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Alexander Flannery

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)
Secondary	Change in Renal Biomarkers	Cystatin C, NGAL will be measured from blood collected at baseline, 24 hours, and at shock resolution.	Until shock resolution, up to 14 days (at baseline, 24 hours, and shock resolution, up to 14 days)
Secondary	Time to discontinuation of catecholamines	Time from enrollment to discontinuation of catecholamines	Until shock resolution, up to 14 days
Secondary	ICU Length of Stay	Number of days in the intensive care unit (ICU).	From enrollment to ICU discharge, up to 28 days following enrollment
Secondary	In-hospital mortality	Assessment of all-cause mortality within hospital admission	Up to 3 months following enrollment
Secondary	Renal replacement therapy-free days	Days free of renal replacement therapy from enrollment up to day 28	Within 28 days of enrollment
Secondary	Safety outcomes	Incidence of venous thromboembolism, arrhythmia, extremity hypoperfusion, delirium, new ischemic event, new infection	Up to 72 hours following shock resolution, no longer than 17 days from enrollment