JMIR Publications

ABSTRACT

Background:

Shock is a life-threatening condition which can lead to multiorgan failure and death. For the treatment of vasoplegic (distributive) shock vasopressors are needed. Angiotensin II (AT II) is a novel vasopressor. Approximately two thirds of patients respond to AT II, and one third do not. AT II is part of the renin-angiotensin-aldosterone system (RAAS). Renin is the limiting enzyme of RAAS, and among other mechanisms its concentration is regulated by AT II concentration through a negative feedback loop. It might be an indicator of response to AT II therapy.

Objective:

We designed a study with a primary objective of a development and standardization of an AT II stress test. which could help predict the responsiveness to AT II in patients with distributive shock regardless of its origin.

Methods:

This is an investigator-initiated, multicentre, parallel, observational clinical study of renin kinetics before and 6 hours after starting an infusion of AT II in severely ill patients with vasoplegic shock and adequate fluid resuscitation. Prior to AT II patients will receive infusion of norepinephrine base ≥0.3 mcg/kg/min and vasopressin 0.03 IU/min. Blood samples for serum renin determination will be obtained immediately prior to and after 6 hours of AT II infusion. We hypothesize that patients who demonstrate a negative renin trend (defined as a decrease in renin concentration 0-6 h) will have a greater number of 28-day organ failure–free days (days without vasopressors, mechanical ventilation, or real-replacement therapy) and 28-day ICU-free days. The primary analysis will assess the association between early renin reduction and organ-failure-free days using Pearson’s correlation coefficient.

Results:

As of April 2026, a total of 55 patients have been enrolled. Data collection is expected to be completed in 2027, after which the results will be analyzed and published.

Conclusions:

The goal of our study is to determine if renin 0-6 h kinetics are associated with clinical outcomes of patients who require AT II. Our study could contribute to the development of a more individualized approach to vasopressor therapy and avoidance of inappropriate use of AT II in patients who are not responders. Clinical Trial: Trial registration Clinicaltrials.gov NCT06539234. Registered on August 1, 2024.