Renin and Renal Biomarker Response to Angiotensin II

Phase 4

Completed

• Conditions: Acute Kidney Injury; Septic Shock
• Interventions: Other: Standard of Care; Drug: Angiotensin II

• Registration Number: NCT04558359
• Lead Sponsor: Alexander Flannery

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-07
• Study First Submitted QC: 2020-09-15
• Study First Posted: 2020-09-22
• Study Start: 2020-10-19
• Primary Completion: 2023-07-24
• Study Completion: 2023-07-30
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-08
• Last Update Posted: 2023-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Standard of Care Cohort	Standard of Care	Patients in this group will receive standard of care treatment.
Angiotensin II Cohort	Angiotensin II	Patients in this group will receive angiotensin II.

Primary Outcome Measures

Name	Time	Method
Change in Plasma Renin Levels	Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)	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.

Secondary Outcome Measures

Name	Time	Method
Change in Plasma Cystatin C	Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)	Cystatin C will be measured from blood collected at baseline, 24 hours, and at shock resolution.
Days to Discontinuation of Catecholamines	Until shock resolution, up to 14 days	Days from enrollment to discontinuation of catecholamines
ICU Length of Stay	From enrollment to ICU discharge, up to 28 days following enrollment	Number of days in the intensive care unit (ICU).
Number of Participants With In-hospital Mortality	Up to 3 months following enrollment	Assessment of all-cause mortality within hospital admission
Renal Replacement Therapy-free Days	Within 28 days of enrollment	Days free of renal replacement therapy from enrollment up to day 28
Number of Participants Experiencing Prespecified Safety Outcomes	Up to 72 hours following shock resolution, no longer than 17 days from enrollment	Incidence of venous thromboembolism, arrhythmia, extremity hypoperfusion, delirium, new ischemic event, new infection
Change in Plasma Neutrophil Gelatinase-associated Lipocalin (NGAL)	Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)	NGAL will be measured from blood collected at baseline, 24 hours, and at shock resolution.

Trial Locations

Locations (1)

University of Kentucky HealthCare Chandler Medical Center; 🇺🇸 Lexington, Kentucky, United States