Clinical trial NCT04558359: Renin and Renal Biomarker Response to Angiotensin II
Official title: Renin and Renal Biomarker Response to Angiotensin II Versus Controls in Septic Shock: An Open-Label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Septic Shock
Acute Kidney Injury
Keywords: Renin
Angiotensin II
vasopressor
sepsis
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2020-09-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Plasma Renin Levels
timeFrame: Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)
Secondary outcomes:
measure: Change in Plasma Cystatin C
timeFrame: Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)
measure: Days to Discontinuation of Catecholamines
timeFrame: Until shock resolution, up to 14 days
measure: ICU Length of Stay
timeFrame: From enrollment to ICU discharge, up to 28 days following enrollment
measure: Number of Participants With In-hospital Mortality
timeFrame: Up to 3 months following enrollment
measure: Renal Replacement Therapy-free Days
timeFrame: Within 28 days of enrollment
measure: Number of Participants Experiencing Prespecified Safety Outcomes
timeFrame: Up to 72 hours following shock resolution, no longer than 17 days from enrollment
measure: Change in Plasma Neutrophil Gelatinase-associated Lipocalin (NGAL)
timeFrame: Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky HealthCare Chandler Medical Center
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Alexander H Flannery, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References: