A Phase 3 interventional study of Angiotensin II and Control in Cardiac Surgery, Vasoplegia and Hyperreninemia, sponsored by Universität Münster. Completed at 1 site in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-03-24.
Sponsored by Universität Münster · Phase 3, Interventional, and Treatment
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.
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.
48 studies on the registry are indexed under Vasoplegia; 19 are open to participants now.
This study's enrollment of 64 is below the median of 110 across 27 interventional studies indexed under Vasoplegia.
Browse Vasoplegia studies →Universität Münster is the lead sponsor of 30 studies on the registry; 19 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Intravenous infusion of max. 80 ng/kg/min Angiotensin II (titrated for each individual patient by effect) over 12 h after start of infusion
Drug: Angiotensin II
Intravenous infusion placebo (matched infusion volume) over 12 h after start of infusion
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 the investigational 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
• 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.
Time frame: 12 hours after start of intervention
Occurence of Acute Kidney Injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Time frame: 72 hours after cardiac surgery
Severity of Acute Kidney Injury
Number of patients with KDIGO stage 1, KDIGO stage 2 or KDIGO stage 3)
Time frame: 72 hours after cardiac surgery
Amount of volume application
Time frame: 12 hours after start of intervention
Fluid status
Time frame: 12 hours after start of intervention
Dose of vasopressor use during intervention
Time frame: During intervention, an average of 12 hours
Creatinine clearance on day one after cardiac surgery
Time frame: One day after cardiac surgery
Free-days through day 28 of vasoactive medications and mechanical ventilation
Time frame: 28 days after cardiac surgery
Renal Recovery
Renal recovery is defined as serum creatinine levels \< 0.5 mg/dL higher than baseline serum creatinine
Time frame: 90 days after cardiac surgery
Mortality
Time frame: 30 days after cardiac surgery
Mortality
Time frame: 60 days after cardiac surgery
Mortality
Time frame: 90 days after cardiac surgery
Length of ICU (Intensive Care Unit) stay
Time frame: up to 90 days after cardiac surgery (until discharge)
Length of hospital stay
Time frame: up to 90 days after cardiac surgery (until discharge)
Use and duration of renal replacement therapy
Number of patients with renal replacement therapy
Time frame: up to 90 days after cardiac surgery
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)
Time frame: 90 days after cardiac surgery
Effect of Angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARBs) use on the effect of angiotensin II
Time frame: 12 hours after intervention
Correlation between the severity of hyperreninemia and the effect of angiotensin II
Time frame: 12 hours after intervention
Plan to share: No
Ran from Dec 2021 to primary completion in Dec 2022, 11 months.
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This study is completed, as verified in Mar 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Angiotensin II
Universität Münster