Cardiac SurgeryPhase 3PAN-AKINCT06615102
Reducing Cardiac-surgery Associated Acute Kidney Injury Occurence by Administering Angiotensin II
A Phase 3 study testing Angiotensin II and Noradrenalin in people with Cardiac Surgery and Vasoplegia, run by Universität Münster at 4 sites in Germany.
Trial summary
The study intervention focuses on exploring the use of angiotensin II as a primary vasopressor compared to norepinephrine in cardiac surgery patients to investigate whether angiotensin II can reduce the occurrence of moderate/severe acute kidney injury (AKI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgery, Vasoplegia
- What is being tested?
- Angiotensin II and Noradrenalin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,022 participants
- Where
- 4 sitesGermany
- Study dates
- 31 Mar 2025to Apr 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cardiac surgery using cardiopulmonary bypass including coronary artery bypass grafting (CABG) surgery, valve surgery, or combined CABG/valve surgery
- Elevated risk of AKI as predicted by a score ≥ 1.5 on the following scale:
- hemoglobin < 130g/l = 2
- creatinine > 1.1 mg/dl = 2
- age > 70 years =1.5
- New York Heart Association Classification (NYHA) 4 =1.5
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- Body Mass Index (BMI) > 30 =1.5
- Adult ≥ 18 years
- Written informed consent
Who cannot join
- Major aortic surgery (aortic arch replacement), transplant surgery, pulmonary thrombendarterectomy, ventricular assist device placement
- Already receiving inotropic/vasopressor support before surgery
- Dialysis dependent
- Pre-existing AKI within the last 30 days
- Pre-existing chronic kidney injury with an eGFR<20 ml/min/1.73m2
- Pre-existing significant hypertension (persistent SBP > 180mmHg)
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- Significant pulmonary hypertension (ePSAP > 70mmHg, mPAP > 40mmHg) with right ventricular systolic dysfunction (graded more severe than mild)
- Hypersensitivity to the active substance or to any of the excipients
- Pregnancy (a negative pregnancy test for women of childbearing age) or breastfeeding women
- Persons with any kind of dependency on the investigator or employed by the sponsor/investigator
- Participation in another interventional trial within the last three months that investigates kidney function
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany4 sites, 4 recruiting
- Recruiting
Deutsches Herzzentrum der Charité
Berlin, 13353
- Recruiting
University Hospital Bonn
Bonn, 53127
- Recruiting
University Medical Center Mainz
Mainz, 55131
- Recruiting
University Hospital Münster
Münster, 49149
About this study
Official title: A Prospective Angiotensin II Versus Noradrenaline Trial for Hypotension Management to Reduce Cardiac-surgery Associated Acute Kidney Injury (PAN-AKI)
The study intervention focuses on exploring the use of angiotensin II as a primary vasopressor compared to norepinephrine in cardiac surgery patients to investigate whether angiotensin II can reduce the occurrence of moderate/severe acute kidney injury (AKI). Despite its potential, as suggested by trials involving surgical patients, there is currently no human data confirming its effectiveness in preventing moderate/severe AKI in this context. The intervention aims to address this gap by evaluating angiotensin II's impact compared to norepinephrine.
Read the detailed description
Acute kidney injury (AKI) is defined by changes in serum creatinine and/or urine output, according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In cardiac surgical patients, the AKI rate is up to 30%, with 1-2% of the patients requiring renal replacement therapy (RRT). Cardiac-surgery associated AKI (CSA-AKI) is associated with increased short- and long-term morbidity and mortality as well as increased hospital costs.
Shock after cardiac surgery is also associated with increased mortality. In the context of cardiac surgery with the use of the cardiopulmonary bypass (CPB), sympathetic nervous system activation and cardiovascular instability are common sequelae. Vasoplegic syndrome is a form of distributive shock that is characterized by low arterial pressure, reduced systemic vascular resistance, and normal or elevated cardiac output. It occurs in 5 to 25% of the patients undergoing cardiac surgery. Patients with vasoplegic shock are at higher risk of organ failure, including AKI, and show increased mortality rates and longer hospital length of stays. Currently, norepinephrine is the established first-line vasopressor for the treatment of vasoplegic shock, but all vasopressors have adverse effects, including myocardial ischemia and arrhythmias. Moreover, in vasoplegic situations, vascular smooth muscle cells may become unresponsive to vasopressors. The underlying mechanisms are complex and include adrenoceptor desensitization, increased nitric oxide (NO) synthesis, activation of adenosine triphosphate-sensitive K+ channels, and vasopressin and corticosteroid deficiency.
Physiologically, the renin-angiotensin-aldosterone system (RAAS) is a hormone system that plays a central role in regulating blood pressure and fluid balance, glomerular filtration rate, and electrolyte levels. Renin, a proteolytic enzyme released by juxtaglomerular cells in response to hypotension, decreases sodium delivery to the distal tubule, activates the sympathetic nervous system, and cleaves angiotensinogen to angiotensin I which is a precursor of the vasoactive angiotensin II. RAAS is regulated by a biofeedback loop. Angiotensin II generation inhibits renin release, whereas renin levels increase when there is insufficient activation of the angiotensin II type 1 receptor. Administration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) and reduced angiotensin II generation cause a corresponding increase in renin levels.
Despite numerous clinical trials using several interventions, a reliable means to prevent AKI remains elusive. Clinical trials focusing on surgical patients suggest that angiotensin II is a potent vasopressor. However, no human data exist whether the application of angiotensin II as a primary vasopressor reduces the occurrence of AKI in patients undergoing cardiac surgery.
- Conditions
- Cardiac Surgery, Vasoplegia
- Being tested
- Angiotensin II, Noradrenalin
- Keywords
- cardiac surgery, acute kidney injury, Angiotensin II
- Medical subject headings
- Vasoplegia, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin IIDrug
Intravenous infusion through a central line according to the patient's situation. Once an infusion is established, the dose will be titrated as frequently as every 5 minutes, as needed, depending on the patient's condition and target MAP.
NoradrenalinDrug
Intravenous infusion through a central line according to the patient's situation. Once an infusion is established, the dose will be titrated as frequently as every 5 minutes, as needed, depending on the patient's condition and target MAP.
| Study group | Role | What they receive |
|---|---|---|
| Angiotensin II | Experimental | Intravenous infusion through a central line according to the patient's situation. Target medium arterial pressure (MAP): >65mmHg Receives: Drug: Angiotensin II |
| Control | Active comparator | Intravenous infusion through a central line according to the patient's situation. Target medium arterial pressure (MAP): >65mmHg Receives: Drug: Noradrenalin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of AKI KDIGO stage 2 or 3 or death within 72 hours after end of cardiac surgery.
Measured: 72 hours after end of surgery
Secondary outcomes (3)
Major Adverse Kidney Events (MAKE90)
- MAKE90 (consisting of mortality, dialysis within 90 days, persistent renal dysfunction (defined as serum creatinine ≥ 2x compared to baseline value at day 90)
Measured: 90 after cardiac surgery
Severity of Acute Kidney Injury
Number of patients with KDIGO stage 1, KDIGO stage 2 or KDIGO stage 3)
Measured: 72 hours after cardiac surgery
Development or progression of chronic kidney injury
Development or progression of chronic kidney disease based on albuminuria, urine creatinine (and the respective ratio) and serum creatinine or death within 120 days
Measured: 90 to 120 days after cardiac surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2024
- Study start31 Mar 2025
- Primary completionJan 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,022 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universität Münster
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation
- Responsible party
- Sponsor
- Investigators
- Alexander Zarbock, MD, Principal investigator, University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06615102
- Sponsor's protocol ID
- UniMS23_0019
- Other IDs
- 542931418
- Acronym
- PAN-AKI
- Status last verified
- Jul 2025
- First submitted
- 23 Sep 2024
- Last updated
- 18 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified patient data will be available up to 3 years after original manuscript publication to researchers with methodologically sound proposals approved by the principal investigator. Supporting Materials:
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Angiotensin II Versus Noradrenaline Trial for Hypotension Management to Reduce Cardiac-surgery Associated Acute Kidney Injury (PAN-AKI)
- ClinicalTrials.gov ID
- NCT06615102
- Acronym / sponsor ID
- PAN-AKI / UniMS23_0019
- Conditions
- Cardiac Surgery, Vasoplegia
- Keywords
- cardiac surgery, acute kidney injury, Angiotensin II
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,022 participants (estimated)
- Lead sponsor
- Universität MünsterUniversity, hospital or other
- Collaborators
- German Research Foundation
- Study start
- 31 Mar 2025 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 26 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study intervention focuses on exploring the use of angiotensin II as a primary vasopressor compared to norepinephrine in cardiac surgery patients to investigate whether angiotensin II can reduce the occurrence of moderate/severe acute kidney injury (AKI). Despite its potential, as suggested by trials involving surgical patients, there is currently no human data confirming its effectiveness in preventing moderate/severe AKI in this context. The intervention aims to address this gap by evaluating angiotensin II's impact compared to norepinephrine.
Detailed description
Acute kidney injury (AKI) is defined by changes in serum creatinine and/or urine output, according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In cardiac surgical patients, the AKI rate is up to 30%, with 1-2% of the patients requiring renal replacement therapy (RRT). Cardiac-surgery associated AKI (CSA-AKI) is associated with increased short- and long-term morbidity and mortality as well as increased hospital costs.
Shock after cardiac surgery is also associated with increased mortality. In the context of cardiac surgery with the use of the cardiopulmonary bypass (CPB), sympathetic nervous system activation and cardiovascular instability are common sequelae. Vasoplegic syndrome is a form of distributive shock that is characterized by low arterial pressure, reduced systemic vascular resistance, and normal or elevated cardiac output. It occurs in 5 to 25% of the patients undergoing cardiac surgery. Patients with vasoplegic shock are at higher risk of organ failure, including AKI, and show increased mortality rates and longer hospital length of stays. Currently, norepinephrine is the established first-line vasopressor for the treatment of vasoplegic shock, but all vasopressors have adverse effects, including myocardial ischemia and arrhythmias. Moreover, in vasoplegic situations, vascular smooth muscle cells may become unresponsive to vasopressors. The underlying mechanisms are complex and include adrenoceptor desensitization, increased nitric oxide (NO) synthesis, activation of adenosine triphosphate-sensitive K+ channels, and vasopressin and corticosteroid deficiency.
Physiologically, the renin-angiotensin-aldosterone system (RAAS) is a hormone system that plays a central role in regulating blood pressure and fluid balance, glomerular filtration rate, and electrolyte levels. Renin, a proteolytic enzyme released by juxtaglomerular cells in response to hypotension, decreases sodium delivery to the distal tubule, activates the sympathetic nervous system, and cleaves angiotensinogen to angiotensin I which is a precursor of the vasoactive angiotensin II. RAAS is regulated by a biofeedback loop. Angiotensin II generation inhibits renin release, whereas renin levels increase when there is insufficient activation of the angiotensin II type 1 receptor. Administration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) and reduced angiotensin II generation cause a corresponding increase in renin levels.
Despite numerous clinical trials using several interventions, a reliable means to prevent AKI remains elusive. Clinical trials focusing on surgical patients suggest that angiotensin II is a potent vasopressor. However, no human data exist whether the application of angiotensin II as a primary vasopressor reduces the occurrence of AKI in patients undergoing cardiac surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Angiotensin II | Experimental | Drug: Angiotensin IIIntravenous infusion through a central line according to the patient's situation. Target medium arterial pressure (MAP): >65mmHg |
| Control | Active comparator | Drug: NoradrenalinIntravenous infusion through a central line according to the patient's situation. Target medium arterial pressure (MAP): >65mmHg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Cardiac surgery using cardiopulmonary bypass including coronary artery bypass grafting (CABG) surgery, valve surgery, or combined CABG/valve surgery
- Elevated risk of AKI as predicted by a score ≥ 1.5 on the following scale:
- Adult ≥ 18 years
- Written informed consent
Key exclusion criteria (11 listed)
- Major aortic surgery (aortic arch replacement), transplant surgery, pulmonary thrombendarterectomy, ventricular assist device placement
- Already receiving inotropic/vasopressor support before surgery
- Dialysis dependent
- Pre-existing AKI within the last 30 days
- Pre-existing chronic kidney injury with an eGFR<20 ml/min/1.73m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin IIIntravenous infusion through a central line according to the patient's situation. Once an infusion is established, the dose will be titrated as frequently as every 5 minutes, as needed, depending on the patient's condition and target MAP. | Drug | Angiotensin II |
| NoradrenalinIntravenous infusion through a central line according to the patient's situation. Once an infusion is established, the dose will be titrated as frequently as every 5 minutes, as needed, depending on the patient's condition and target MAP. | Drug | Control |
Primary outcome
Rate of AKI KDIGO stage 2 or 3 or death within 72 hours after end of cardiac surgery.
Time frame: 72 hours after end of surgery
3 secondary outcomes
Major Adverse Kidney Events (MAKE90)
Time frame: 90 after cardiac surgery
Severity of Acute Kidney Injury
Time frame: 72 hours after cardiac surgery
Development or progression of chronic kidney injury
Time frame: 90 to 120 days after cardiac surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2025.
- Individual participant dataSharing planned: Yes. Deidentified patient data will be available up to 3 years after original manuscript publication to researchers with methodologically sound proposals approved by the principal investigator. Supporting Materials:
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alexander Zarbock, MD principal investigator
University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Angiotensin II and Noradrenalin in people with Cardiac Surgery and Vasoplegia, run by Universität Münster at 4 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexander Zarbock, MD (+49-251-8347252, PAN-AKI@ukmuenster.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of AKI KDIGO stage 2 or 3 or death within 72 hours after end of cardiac surgery. (time frame: 72 hours after end of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2025.