Reducing Acute Kidney Injury Occurence by Administering Angiotensin II

NCT ID: NCT05199493

Last Updated: 2023-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-27
• Study Completion Date: 2023-03-19

Brief Summary

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.

Detailed 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.

Conditions

Cardiac Surgery; Vasoplegia; Hyperreninemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Angiotensin II

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

Group Type: EXPERIMENTAL

Angiotensin II

Intervention Type: DRUG

Patients with Delta-renin \>= 3.7 micro-unit/mL are at high risk for AKI. Patients who have a high delta-renin and a postoperative hypotension requiring vasopressors ad will be randomized. After randomization patients will receive intravenous infusion with the investigational drug.

Control

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

Group Type: PLACEBO_COMPARATOR

Control

Intervention Type: DRUG

Patients with Delta-renin \>= 3.7 micro-unit/mL are at high risk for AKI. Patients who have a high delta-renin and a postoperative hypotension requiring vasopressors ad will be randomized. After randomization patients will receive intravenous infusion with placebo

Interventions

Angiotensin II

Patients with Delta-renin \>= 3.7 micro-unit/mL are at high risk for AKI. Patients who have a high delta-renin and a postoperative hypotension requiring vasopressors ad will be randomized. After randomization patients will receive intravenous infusion with the investigational drug.

Intervention Type: DRUG

Control

Patients with Delta-renin \>= 3.7 micro-unit/mL are at high risk for AKI. Patients who have a high delta-renin and a postoperative hypotension requiring vasopressors ad will be randomized. After randomization patients will receive intravenous infusion with placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Research Foundation

OTHER

Sponsor Role: collaborator

Universität Münster

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexander Zarbock, MD

Role: STUDY_CHAIR

University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy

Locations

University Hospital Muenster

Münster, , Germany

Countries

Germany

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

2021-003088-87

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

06-AnIt-20

Identifier Type: OTHER

Identifier Source: secondary_id

WWU20_0016

Identifier Type: -

Identifier Source: org_study_id