Angiotensin II to reduce kidney injury after heart surgery

A Prospective Angiotensin II Versus Noradrenaline Trial for Hypotension Management to Reduce Cardiac-surgery Associated Acute Kidney Injury (PAN-AKI)

This trial tests whether angiotensin II, used as the primary blood-pressure medicine instead of norepinephrine after cardiac surgery with cardiopulmonary bypass, can lower the chance of moderate or severe acute kidney injury in adults at higher risk.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1022 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Universität Münster (Academic / other)
• Locations: 4 sites (Berlin and 3 other locations)
• Trial ID: NCT06615102 on ClinicalTrials.gov

What this trial studies

This is a phase 3, randomized, controlled trial comparing angiotensin II versus norepinephrine as the first-line vasopressor in adults undergoing cardiac surgery with cardiopulmonary bypass who are at elevated risk for acute kidney injury. The main outcome is the occurrence of moderate or severe AKI defined by KDIGO creatinine and urine-output criteria, with secondary outcomes including need for renal replacement therapy, mortality, and length of stay. Patients with typical cardiac procedures (CABG, valve, or combined) who meet a predefined AKI risk score and provide consent are eligible, while those with major aortic/transplant surgery, preoperative vasopressor use, dialysis dependence, recent AKI, or very low eGFR are excluded. The trial is conducted at multiple German academic centers and collects perioperative hemodynamic and renal function data to compare renal outcomes between the two vasopressor strategies.

Who should consider this trial

Good fit: Adults (≥18) having cardiac surgery with cardiopulmonary bypass (CABG, valve, or combined) who score ≥1.5 on the trial's AKI risk scale and can give written informed consent are ideal candidates.

Not a fit: Patients undergoing major aortic or transplant procedures, those already on vasopressors before surgery, dialysis-dependent patients, recent AKI, or with very low eGFR or severe pulmonary hypertension are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, using angiotensin II as the primary vasopressor could reduce rates of moderate or severe AKI after cardiac surgery, potentially lowering the need for dialysis, complications, and hospital stays.

How similar studies have performed: Previous surgical and shock-patient trials have shown angiotensin II can raise blood pressure and suggest possible renal benefits, but there is no definitive human evidence yet that it prevents moderate or severe cardiac-surgery associated AKI.

Eligibility criteria

Inclusion Criteria:

1. Cardiac surgery using cardiopulmonary bypass including coronary artery bypass grafting (CABG) surgery, valve surgery, or combined CABG/valve surgery
2. Elevated risk of AKI as predicted by a score ≥ 1.5 on the following scale:

   1. hemoglobin \< 130g/l = 2
   2. creatinine \> 1.1 mg/dl = 2
   3. age \> 70 years =1.5
   4. New York Heart Association Classification (NYHA) 4 =1.5
   5. Body Mass Index (BMI) \> 30 =1.5
3. Adult ≥ 18 years
4. Written informed consent

Exclusion Criteria:

1. Major aortic surgery (aortic arch replacement), transplant surgery, pulmonary thrombendarterectomy, ventricular assist device placement
2. Already receiving inotropic/vasopressor support before surgery
3. Dialysis dependent
4. Pre-existing AKI within the last 30 days
5. Pre-existing chronic kidney injury with an eGFR\<20 ml/min/1.73m2
6. Pre-existing significant hypertension (persistent SBP \> 180mmHg)
7. Significant pulmonary hypertension (ePSAP \> 70mmHg, mPAP \> 40mmHg) with right ventricular systolic dysfunction (graded more severe than mild)
8. Hypersensitivity to the active substance or to any of the excipients
9. Pregnancy (a negative pregnancy test for women of childbearing age) or breastfeeding women
10. Persons with any kind of dependency on the investigator or employed by the sponsor/investigator
11. Participation in another interventional trial within the last three months that investigates kidney function

Where this trial is running

Berlin and 3 other locations

• Deutsches Herzzentrum der Charité — Berlin, Germany (Recruiting)
• University Hospital Bonn — Bonn, Germany (Recruiting)
• University Medical Center Mainz — Mainz, Germany (Recruiting)
• University Hospital Münster — Münster, Germany (Recruiting)

Study contacts

• Principal investigator: Alexander Zarbock, MD — University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy
• Study coordinator: Alexander Zarbock, MD

Conditions Cardiac Surgery; Vasoplegia; cardiac surgery; acute kidney injury; Angiotensin II