Renin Kinetics and Hemodynamic Response During Treatment of Vasoplegic Shock With Angiotensin II (TENSINTEST): Protocol for a Multicenter Observational Study

Abstract Background Shock is a life-threatening condition that can lead to multiorgan failure and death. Vasopressors are needed for the treatment of vasoplegic (distributive) shock. 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 the 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 developing and standardizing 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, multicenter observational clinical study of renin kinetics before and 6 hours after starting an infusion of AT II in patients with vasoplegic shock and adequate fluid resuscitation who are severely ill. Prior to AT II, patients will receive an infusion of norepinephrine base of 0.3 mcg per kilogram per minute or higher, and vasopressin of 0.03 IU per minute according to institutional protocol. 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 trend in relative renin ratio (defined as renin plasma concentration at baseline or at 6 hours after treatment with AT II divided by upper normal concentration of plasma renin [50 mU/L]) will have a greater number of 28-day organ failure–free days (days without vasopressors, mechanical ventilation, or renal replacement therapy). The primary analysis will assess the association between early renin reduction and organ failure–free days using an adjusted proportional odds ordinal regression model. Results The research was funded in December 2024. After obtaining ethics approval in July 2025, data collection started on August 1, 2025. As of July 2026, a total of 70 patients had 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 whether renin 0-6 h kinetics (difference between renin levels before and 6 hours after starting an AT II infusion) are associated with clinical outcomes in 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, allowing earlier discontinuation of AT II and consideration of alternative therapies.