Reducing Acute Kidney Injury Occurence by Administering Angiotensin II

Cardiac Surgery Clinical Trial

— AIDED  

Official title:

Biomarker-guided Implementation of Angiotensin-II (AT-II) to Reduce the Occurrence of Kidney Damage After Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05199493
• Other study ID #: WWU20_0016
• Secondary ID: 2021-003088-8706
• Status: Completed
• Phase: Phase 3
• Start date: December 27, 2021
• Est. completion date: March 19, 2023

Study information

• Verified date: March 2023
• Source: Westfälische Wilhelms-Universität Münster
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: March 19, 2023
• Est. primary completion date: December 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Cardiac Surgery
• Vasoplegia

Intervention

Drug:
• 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.
• 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

Locations

Country	Name	City	State
Germany	University Hospital Muenster	Münster

Sponsors (2)

Lead Sponsor	Collaborator
Westfälische Wilhelms-Universität Münster	German Research Foundation

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	• kidney damage after cardiac surgery identified by the difference between [TIMP-2]*[IGFBP7] levels 12h after randomization and [TIMP-2]*[IGFBP7] levels at randomization	The presence of tissue inhibitor of metalloproteinases (TIMP-2) and insulin-like growth-factor binding protein 7 (IGFBP7) in the urine will be measured.	12 hours after start of intervention
Secondary	Occurence of Acute Kidney Injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria		72 hours after cardiac surgery
Secondary	Severity of Acute Kidney Injury	Number of patients with KDIGO stage 1, KDIGO stage 2 or KDIGO stage 3)	72 hours after cardiac surgery
Secondary	Amount of volume application		12 hours after start of intervention
Secondary	Fluid status		12 hours after start of intervention
Secondary	Dose of vasopressor use during intervention		During intervention, an average of 12 hours
Secondary	Creatinine clearance on day one after cardiac surgery		One day after cardiac surgery
Secondary	Free-days through day 28 of vasoactive medications and mechanical ventilation		28 days after cardiac surgery
Secondary	Renal Recovery	Renal recovery is defined as serum creatinine levels < 0.5 mg/dL higher than baseline serum creatinine	90 days after cardiac surgery
Secondary	Mortality		30 days after cardiac surgery
Secondary	Mortality		60 days after cardiac surgery
Secondary	Mortality		90 days after cardiac surgery
Secondary	Length of ICU (Intensive Care Unit) stay		up to 90 days after cardiac surgery (until discharge)
Secondary	Length of hospital stay		up to 90 days after cardiac surgery (until discharge)
Secondary	Use and duration of renal replacement therapy	Number of patients with renal replacement therapy	up to 90 days after cardiac surgery
Secondary	Major adverse kidney events (MAKE)	Major adverse kidney events consisting of mortality, dialysis dependency, persistent renal dysfunction (defined as serum creatinine = 2x compared to baseline value)	90 days after cardiac surgery
Secondary	Effect of Angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARBs) use on the effect of angiotensin II		12 hours after intervention
Secondary	Correlation between the severity of hyperreninemia and the effect of angiotensin II		12 hours after intervention