Renin and Renal Biomarker Response to Angiotensin II

Sponsor

Alexander Flannery (Other)

Overall Status

Recruiting

CT.gov ID

NCT04558359

Collaborator

(none)

Enrollment

Location

Arms

26.4

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock Acute Kidney Injury	Other: Standard of Care Drug: Angiotensin II	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 19, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard of Care Cohort Patients in this group will receive standard of care treatment.	Other: Standard of Care These patients will receive standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured.
Experimental: Angiotensin II Cohort Patients in this group will receive angiotensin II.	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.

Arm

Intervention/Treatment

Active Comparator: Standard of Care Cohort

Patients in this group will receive standard of care treatment.

Other: Standard of Care

These patients will receive standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured.

Experimental: Angiotensin II Cohort

Patients in this group will receive angiotensin II.

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.

Outcome Measures

Primary Outcome Measures

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

Change in Renal Biomarkers [Until shock resolution, up to 14 days (at baseline, 24 hours, and shock resolution, up to 14 days)]
Cystatin C, NGAL will be measured from blood collected at baseline, 24 hours, and at shock resolution.
Time to discontinuation of catecholamines [Until shock resolution, up to 14 days]
Time 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).
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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