Reducing Acute Kidney Injury Occurence by Administering Angiotensin II

NCT05199493 | Completed Phase 3 DMC

• 3 other identifiers: WWU20_00162021-003088-8706-AnIt-20
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cardiac Surgery; Vasoplegia; Hyperreninemia

Keywords

Cardiac Surgery; Acute kidney injury; Biomarker; Angiotensin II; Renin

Outcome Measures

Primary Outcomes (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.

  12 hours after start of intervention

Secondary Outcomes (17)

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

  72 hours after cardiac surgery

• Severity of Acute Kidney Injury

  72 hours after cardiac surgery

• Amount of volume application

  12 hours after start of intervention

• Fluid status

  12 hours after start of intervention

• Dose of vasopressor use during intervention

  During intervention, an average of 12 hours

Study Arms (2)

Angiotensin II

EXPERIMENTAL

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

Control

PLACEBO COMPARATOR

Intravenous infusion placebo (matched infusion volume) over 12 h after start of infusion

Drug: Control

Interventions

Angiotensin II 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 the investigational drug.

Angiotensin II

Control 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

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universität Münster: lead
• German Research Foundation: collaborator

Study Sites (1)

University Hospital Muenster

Münster, 48149, Germany

Location

MeSH Terms

Conditions

Vasoplegia; Acute Kidney Injury

Interventions

Angiotensin II

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Alexander Zarbock, MD

  University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: January 20, 2022
• Study Start: December 27, 2021
• Primary Completion: December 19, 2022
• Study Completion: March 19, 2023
• Last Updated: March 24, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)