Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ongoing, recruiting
Participants planned
1,022
Countries
1
Sites
15
Acute kidney injury
To investigate the effect of angiotensin II as primary vasopressor on the occurence of moderate or severe acute kidney injury within 72 hours after cardiac surgery
Key facts
- Sponsor
- Universitaet Muenster
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]
- Trial duration
- 31 Mar 2025 → ongoing
- Decision date (initial)
- 2025-02-06
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- PAION Deutschland GmbH · Deutsche Forschungsgemeinschaft
External identifiers
- EU CT number
- 2024-517771-21-00
- ClinicalTrials.gov
- NCT06615102
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To investigate the effect of angiotensin II as primary vasopressor on the occurence of moderate or severe acute kidney injury within 72 hours after cardiac surgery
Secondary objectives 2
- To investigate the effect of angiotensin II as primary vasopressor on long-term Major Adverse Kidney Events MAKE at day 90 (MAKE90)
- To investigate the effect of angiotensin II as primary vasopressor on the development or progression of chronic kidney injury
Conditions and MedDRA coding
Acute kidney injury
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10017501 | Functional disturbances following cardiac surgery | 10022117 |
| 20.1 | LLT | 10080266 | Stage 1 acute kidney injury | 10038359 |
| 26.0 | PT | 10069339 | Acute kidney injury | 100000004857 |
| 20.1 | LLT | 10080269 | Stage 2 acute kidney injury | 10038359 |
| 20.1 | LLT | 10080271 | Stage 3 acute kidney injury | 10038359 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Angiotensin II vs Norepinephrine in PAN-AKI allocation and interim analysis trial.
We will enroll approximately 1022 (up to 1222 patients based on the results of the interim analysis) adult patients scheduled for cardiac surgery (CABG surgery, valve surgery and combined CABG/valve surgery) with CPB who meet the inclusion and none of the exclusion criteria, and will randomly assign them in a 1:1 ratio to receive either angiotensin II (intervention group) or norephinephrine (control group). Randomization will be stratified by site and type of surgical procedure (coronary artery bypass graft, valve surgery, combined CABG/valve surgery).
|
Randomised Controlled | Double | [{"id":131128,"code":3,"name":"Monitor"},{"id":131131,"code":1,"name":"Subject"},{"id":131132,"code":4,"name":"Analyst"},{"id":131129,"code":5,"name":"Carer"},{"id":131130,"code":2,"name":"Investigator"}] | Angiotensin: The infusion bag containing Angiotensin II 0.01 mg/ml Control: The Infusion bag containing Norephinephrin 0.1 mg/ml |
Regulatory references
- Plan to share IPD
- Yes
- IPD plan description
- Anonymized individual participant will be used for meta analyses
| EU CT number | Title | Sponsor |
|---|---|---|
| 2021-003088-87 | Biomarker-guided implementation of angiotensin-II (AT-II) to reduce the occurrence of kidney damage after cardiac surgery , Biomarker-gesteuerter Einsatz von Angiotensin II zur Verringerung des Auftretens einer akuten Nierenschädigung (AKI) nach Herzoperationen, Biomarker-gesteuerter Einsatz von Angiotensin II zur Verringerung des Auftretens einer akuten Nierenschädigung (AKI) nach Herzoperationen |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- 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: a. hemoglobin < 130g/l = 2 b. creatinine > 1.1 mg/dl = 2 c. age > 70 years =1.5 d. NYHA 4 =1.5 e. BMI > 30 =1.5
- Adult ≥ 18 years
- Written informed consent
Exclusion criteria 11
- 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)
- 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 of angiotensin II and norepinephrine (e.g. sodium metabisulfite, sulfite, chlorobutanol hemihydrate and sodium chloride and water)
- 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Rate of AKI KDIGO stage 2 or 3 or death within 72 hours after cardiac surgery
Secondary endpoints 2
- MAKE90 (consisting of mortality, any dialysis within 90 days, persistent renal dysfunction (defined as > 25% eGFR reduction to baseline value at day 90)
- Development or progression of chronic kidney disease based on albuminuria and on two serum creatinine measurements between day 90 and 120
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Giapreza 2.5 mg/ml concentrate for solution for infusion
PRD9007224 · Product
- Active substance
- Angiotensin Ii
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 64.8 µg/Kg microgram(s)/kilogram
- Max total dose
- 180 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- C01CX09 — -
- Marketing authorisation
- EU/1/19/1384/003
- MA holder
- PAION PHARMA GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
SCP14402750 · ATC
- Active substance
- Noradrenaline Tartrate
- Substance synonyms
- NOREPINEPHRINE BITARTRATE, LEVARTERENOL ACID TARTRATE, ARTERENOL ACID TARTRATE, NOREPINEPHRINE HYDROGEN TARTRATE
- Route of administration
- INTRAVENOUS PERFUSION USE
- Max daily dose
- 4.3 mg/kg milligram(s)/kilogram
- Max total dose
- 13 mg/kg milligram(s)/kilogram
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- C01CA03 — NOREPINEPHRINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitaet Muenster
- Sponsor organisation
- Universitaet Muenster
- Address
- Schlossplatz 2, Schlossbezirk Schlossbezirk
- City
- Muenster
- Postcode
- 48149
- Country
- Germany
Scientific contact point
- Organisation
- Universitaet Muenster
- Contact name
- Principal Coordinating Investigator
Public contact point
- Organisation
- Universitaet Muenster
- Contact name
- Principal Coordinating Investigator
Locations
1 EU/EEA country · 15 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruiting | 1,022 | 15 |
| Rest of world | — | 0 | — |
Investigational sites
Universitaetsklinikum Augsburg
Department of Anesthesiology and Intensive Care Medicine, Stenglinstrasse 2, Kriegshaber, Augsburg
Friedrich-Schiller-Universitaet Jena
Department of Anesthesiology and Intensive Care Medicine, Am Klinikum 1, Lobeda, Jena
Universitaet Muenster
Department of Anesthesiology, Intensive Care and Pain Medicine, Albert-Schweitzer-Campus 1, Sentrup, Muenster
Universitaetsmedizin Goettingen
Department of Anesthesiology, Robert-Koch-Strasse 40, Weende, Goettingen
Justus-Liebig-Universitaet Giessen
Klinik für Herz-, Kinderherz- und Gefäßchirurgie, Rudolf-Buchheim-Strasse 7, 35392, Giessen
Charite Universitaetsmedizin Berlin KöR
Deutsches Herzzentrum der Charité - Klinik für Kardioanästhesiologie und Intensivmedizin, Augustenburger Platz 1, Wedding, Berlin
Universitaetsklinikum Tuebingen AöR
Department of Anesthesiology and Intensive Care Medicine, Hoppe-Seyler-Strasse 3, Nordstadt, Tuebingen
Herzzentrum Dresden GmbH Universitaetsklinik
Herzzentrum Dresden, TU Dresden, Fetscherstrasse 76, Johannstadt-Nord, Dresden
Deutsches Herzzentrum Muenchen Klinikum Der Technischen Universitaet Muenchen
Klinik für Herz- und Gefäßchirurgie, Lazarettstrasse 36, Neuhausen-Nymphenburg, Munich
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department of Anesthesiology, Langenbeckstrasse 1, Oberstadt, Mainz
Universitaetsklinikum Bonn AöR
University Hospital Bonn; Klinik für Anästhesiologie und Operative Intensivmedizin, Venusberg-Campus 1, Venusberg, Bonn
Universitaetsklinikum Essen AöR
Klinik für Thorax- und Kardiovaskuläre Chirurgie, Westdeutsches Herz- und Gefässzentrum Essen, Hufelandstrasse 55, Holsterhausen, Essen
Klinikgruppe Dr. Guth GmbH & Co. KG
Intensive Care Medicine; Heart- and Diabetes Center, Greifswalder Strasse 11, 17495, Karlsburg
University Medical Center Hamburg-Eppendorf
Klinik und Poliklinik für Anästhesiologie Zentrum für Anästhesiologie und Intensivmedizin, Martinistrasse 52, Eppendorf, Hamburg
Universitaetsklinikum Wuerzburg AöR
Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Oberduerrbacher Strasse 6, Grombuehl, Wuerzburg
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2025-03-31 | 2025-03-31 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-517771-21-00 | 2.1 |
| Recruitment arrangements (for publication) | K1_Recruitment_arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 1.3 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Giapreza | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC_Arterenol 1 ml_25 ml | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis EN 2024-517771-21-00 | 2.1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-12-03 | Germany | Acceptable 2025-02-03
|
2025-02-06 |
| 2 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-02-24 | Germany | Acceptable 2025-03-18
|
2025-03-20 |
| 3 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-06-17 | Germany | Acceptable 2025-07-07
|
2025-07-09 |