Reducing Acute Kidney Injury Occurence by Administering Angiotensin II (AIDED)

Universität Münster

Status and phase: Completed; Phase 3

Conditions: Vasoplegia; Cardiac Surgery; Hyperreninemia

Treatments: Drug: Angiotensin II; Drug: Control

Study type: Interventional

Funder types: Other

Identifiers

NCT05199493

06-AnIt-20 (Other Identifier)

2021-003088-87 (EudraCT Number)

WWU20_0016

Details and patient eligibility

About

The aim of this study is to evaluate whether adding angiotensin II to the standard of care is superior compared to the standard of care alone with respect to kidney damage (personalized approach) after cardiac surgery.

Full description

Vasoplegic syndrome is a form of distributive shock that is characterized by low arterial pressure with reduced systemic vascular resistance and normal or elevated cardiac output that occurs in 5 to 25% of patients undergoing cardiac surgery. Patients with vasoplegic shock after cardiac surgery are at higher risk of organ failure, including acute kidney injury (AKI). Postsurgical AKI is associated with several adverse outcomes. Attempts to prevent AKI have largely been futile so far. Prior studies often started with the interventions after an AKI event, when a decline of kidney function (i.e. glomerular filtration rate) was already established. Application of norepinephrine is currently considered as the first-line therapy for vasoplegic shock, but all catecholamines have adverse effects, including myocardial ischemia and arrhythmias. In a recent observational trial, we demonstrated that there is a dysregulation in the renin-angiotensin-aldosterone system (RAAS) likely caused by a reduced angiotensin-converting enzyme (ACE) activity after cardiac surgery. Elevated renin levels identified patients at risk for AKI and were associated with cardiovascular instability and increased AKI rate after cardiac surgery. Furthermore, elevated renin levels could be used to identify high-risk patients for cardiovascular instability and AKI who would benefit from timely intervention with angiotensin II that could improve their outcomes. Therefore, the application of angiotensin II to treat a postoperative hypotension would mean a hormone substitution.Shock after cardiac surgery is associated with increased mortality. Cardiopulmonary bypass (CPB) represents a common clinical setting of sympathetic nervous system activation and cardiovascular instability. Vasoplegia is a form of distributive shock that is characterized by low arterial pressure with reduced systemic vascular resistance and normal or elevated cardiac output. It occurs in 5 to 25% of patients undergoing cardiac surgery. Patients with vasoplegia after cardiac surgery are at higher risk of organ failure, including AKI, and have an increased mortality rate and longer hospital length of stay.

Clinical trials focusing on septic patients suggest that AT-II is a potent vasopressor. However, no human data exist whether the application of AT-II in cardiac surgery patients with y hyperreninemia high-risk patients identified by renin levels (individualized approach) reduces kidney damage and improves kidney function after cardiac surgery.

Enrollment: 64 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients undergoing cardiac surgery with CPB
• Cardiac index 2.1l/min per square meter
• Written informed consent
• D-renin (difference between post- and preoperative) ≥ 3.7 micro Unit/ml 4 h after CPB
• Postoperative hypotension requiring vasopressors

Exclusion criteria

• Preexisting AKI (stage 1 and higher)
• Patients with cardiac assist devices
• Pregnant women, nursing women and women of childbearing potential
• Known (Glomerulo-) Nephritis, interstitial nephritis or vasculitis
• chronic kidney disease with estimated glomerular filtration rate (eGFR) < 30 ml/min
• Dialysis dependent chronic kidney disease
• Prior kidney transplant within the last to 12 months
• Emergency surgery in the context of an acute coronary syndrome
• Hypersensitivity to the active substance, or to any of the excipients of the study medication
• Bronchospasm
• Liver failure
• Mesenteric ischemia
• Participation in another intervention trial in the past 3 months
• Persons with any kind of dependency on the investigator or employed by the institution responsible or investigator
• Persons held in an institution by legal or official order

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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64 participants in 2 patient groups, including a placebo group

Angiotensin II

Experimental group

Description:

Intravenous infusion of max. 80 ng/kg/min Angiotensin II (titrated for each individual patient by effect) over 12 h after start of infusion

Treatment:

Drug: Angiotensin II

Control

Placebo Comparator group

Description:

Intravenous infusion placebo (matched infusion volume) over 12 h after start of infusion

Treatment:

Drug: Control