Shock is a major risk factor for mortality among patients admitted to intensive care units (ICUs). Since various hemodynamic strategies uniformly delivered to patients with shock have failed to improve clinically relevant outcomes, individualized approaches for shock supported by robust evidence are required. This study will be a prospective, multicenter, parallel-group, single-blind, randomized controlled trial. The investigators will randomly assign 800 critically ill patients requiring norepinephrine infusion to the renin-guided or usual care groups. The investigators hypothesize that renin-guided hemodynamic management, compared to usual care, can reduce a composite of mortality and acute kidney injury (AKI) progression in patients requiring vasopressor support.
Shock is a common cause of death among patients admitted to intensive care units. Acute kidney injury (AKI) frequently occurs in patients with shock (3, 4). Maintaining adequate perfusion pressure and oxygen delivery is crucial in the hemodynamic management of shock (5). Several randomized controlled trials have evaluated the effect of various hemodynamic protocols treating shock patients with a "one size fits all" approach. However, such protocols did not reduce mortality (6-8). The task force of the surviving sepsis campaign identified the personalization of sepsis resuscitation as a research priority (9). Moreover, a large RCT showed that personalizing blood pressure targets reduced the risk of postoperative organ dysfunction in patients undergoing major surgery (10). These findings suggest that applying individualized hemodynamic strategy may optimize shock treatment and potentially improve outcomes (11). Recent studies have investigated renin as a novel marker of tissue hypoperfusion in critically ill patients. While serum lactate level has been the most common and validated marker for tissue hypoperfusion (12), several studies are now suggesting that renin may predict mortality better than lactate in critically ill patients (13, 14). Notably, relative renin increase is associated with adverse clinical outcomes and shock reversal has been shown to decrease renin concentration (15). The investigators aim to perform the Randomized Evaluation of persoNalized hemodynamIc maNagement based on serum renin concentration (RENIN) trial to test the hypothesis that renin-guided hemodynamic management can reduce a composite of mortality and acute kidney injury (AKI) progression during the hospital stay in patients requiring vasopressors compared with usual care.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
800
If normalization of renin levels is achieved (values within the normal laboratory range), we will continue with usual care according to local protocols.
Standard of care
University Hospital Dubrava
Dubrava, Croatia
RECRUITINGOspedale Mater Domini
Catanzaro, Calabria, Italy
NOT_YET_RECRUITINGIRCCS Ospedale San Raffaele
Milan, Italy
RECRUITINGA composite of mortality or AKI progression at 30 days after randomization.
The primary outcome will be a composite of mortality or AKI progression at 30 days after randomization. We will define AKI progression as increasing at least two AKI stages compared to the AKI stage at study enrollment. We will define and stage AKI according to the current international criteria, the KDIGO guidelines (16). We will use both creatinine and urine output criteria.
Time frame: 30 days
All-cause mortality at intensive care unit discharge, hospital discharge, and 90 days after randomization.
Time frame: 90 days
The need for and duration of vasopressors at 30 days after randomization
Deaths within the initial 30 days were assigned 30 days of duration of vasopressors at day 30.
Time frame: 30 days
Days alive and free from mechanical ventilation
Deaths within the initial 30 days were assigned zero days alive and free from mechanical ventilation at day 30.
Time frame: 30 days
Day alive and free from renal replacement therapy.
Deaths within the initial 30 days were assigned zero days alive and free from renal replacement therapy at day 30.
Time frame: 30 days
Days alive and outside the ICU.
Deaths within the initial 30 days were assigned zero days alive and outside the ICU at day 30.
Time frame: 30 days
Duration of hospital stay.
Deaths within the initial 30 days were assigned 30 days of hospital stay.
Time frame: 30 days
Major adverse kidney events at day 90.
Major adverse kidney events are defined as a composite of death, the dependence of renal replacement therapy, and persistent renal dysfunction (defined as a 25% or greater decline in estimated glomerular filtration rate (eGFR) from the baseline) (17).
Time frame: 90 days
Quality of life at day 90.
EQ-5D-5L is the most widely used measure of health-related quality of life.
Time frame: 90 days
Adverse events during hospital stay.
Adverse events will include atrial fibrillation, acute myocardial infarction, ventricular fibrillation or tachycardia, digital ischemia, mesenteric ischemia, bleeding, reintubation, need for non-invasive ventilation, delirium, and stroke.
Time frame: 30 days
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