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Cardiac SurgeryPhase 3AIDEDNCT05199493

Reducing Acute Kidney Injury Occurence by Administering Angiotensin II

A Phase 3 study testing Angiotensin II in people with Cardiac Surgery and Vasoplegia, run by Universität Münster at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cardiac Surgery, Vasoplegia, Hyperreninemia
What is being tested?
Angiotensin II
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
64 participants
Where
1 siteGermany
Study dates
27 Dec 2021to 19 Mar 2023
Phase
Phase 3
Are there results?
None posted in the registry

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

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • University Hospital Muenster

    Münster, 48149

Other trials in Germany

About this study

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

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.

Read the 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.

Being tested
Angiotensin II, Control
Keywords
Cardiac Surgery, Acute kidney injury, Biomarker, Angiotensin II, Renin
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

    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.

  • ControlDrug

    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

Study groups in NCT05199493
Study groupRoleWhat they receive
Angiotensin IIExperimentalIntravenous infusion of max. 80 ng/kg/min Angiotensin II (titrated for each individual patient by effect) over 12 h after start of infusion
Receives: Drug: Angiotensin II
ControlPlacebo comparatorIntravenous infusion placebo (matched infusion volume) over 12 h after start of infusion
Receives: Drug: Control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. • 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.

    Measured: 12 hours after start of intervention

Secondary outcomes (17)

  1. Occurence of Acute Kidney Injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria

    Measured: 72 hours after cardiac surgery

  2. 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

  3. Amount of volume application

    Measured: 12 hours after start of intervention

  4. Fluid status

    Measured: 12 hours after start of intervention

  5. Dose of vasopressor use during intervention

    Measured: During intervention, an average of 12 hours

  6. Creatinine clearance on day one after cardiac surgery

    Measured: One day after cardiac surgery

  7. Free-days through day 28 of vasoactive medications and mechanical ventilation

    Measured: 28 days after cardiac surgery

  8. Renal Recovery

    Renal recovery is defined as serum creatinine levels < 0.5 mg/dL higher than baseline serum creatinine

    Measured: 90 days after cardiac surgery

  9. Mortality

    Measured: 30 days after cardiac surgery

  10. Mortality

    Measured: 60 days after cardiac surgery

  11. Mortality

    Measured: 90 days after cardiac surgery

  12. Length of ICU (Intensive Care Unit) stay

    Measured: up to 90 days after cardiac surgery (until discharge)

  13. Length of hospital stay

    Measured: up to 90 days after cardiac surgery (until discharge)

  14. Use and duration of renal replacement therapy

    Number of patients with renal replacement therapy

    Measured: up to 90 days after cardiac surgery

  15. 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)

    Measured: 90 days after cardiac surgery

  16. Effect of Angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARBs) use on the effect of angiotensin II

    Measured: 12 hours after intervention

  17. Correlation between the severity of hyperreninemia and the effect of angiotensin II

    Measured: 12 hours after intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2022
  2. Study start27 Dec 2021
  3. Primary completion19 Dec 2022
  4. Study completion19 Mar 2023

Resources

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
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05199493
Sponsor's protocol ID
WWU20_0016
Other IDs
2021-003088-87, 06-AnIt-20
Acronym
AIDED
Status last verified
Mar 2023
First submitted
2 Dec 2021
Last updated
24 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Angiotensin II in people with Cardiac Surgery and Vasoplegia, run by Universität Münster at 1 site 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 5 inclusion and 15 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: finished, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. Some participants in this study may receive a placebo. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

• kidney damage after cardiac surgery identified by the difference between [TIMP-2]*[IGFBP7] levels 12h after randomization and [TIMP-2]*[IGFBP7] levels at randomization (time frame: 12 hours after start of intervention). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05199493.

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 24 Mar 2023.

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