Clinical Studies
As part of our research activities on systemic inflammation, several clinical trials are currently being conducted by KFO342 and its project managers. The goal of these studies is to gain a better understanding of the pathogenesis of diseases associated with systemic inflammation and, based on this, to develop potential therapeutic approaches.
Current clinical trials
Title of the Study : A Prospective Angiotensin II versus Noradrenaline trial for Hypotension management to reduce cardiac surgery-associated Acute Kidney Injury (PAN-AKI)
Synopsis: Acute kidney injury is a common complication following heart surgery and affects approximately 30% of all cardiac surgery patients. The causes are varied, and low blood pressure is a contributing factor. Hypotension requiring intervention occurs very frequently during anesthesia and while the patient is on the heart-lung machine. Vasopressors are used as standard treatment for this condition. This project is now investigating another vasopressor called angiotensin II, which is already approved for the treatment of hypotension in patients with septic shock. The aim is to determine whether this investigational drug can also be used to treat cardiac surgery patients and whether it might offer advantages over standard therapy. The study aims to close another gap in the prevention of postoperative acute kidney injury in high-risk patients.
Publications:
No publications to date; project is still ongoing
Study Start and End:
Start: 2025-03-31; projected end: 2027
Contact Persons: Univ.-Prof. Dr. med. Alexander Zarbock, Dr. med. Ludwig Maximilian Schöne
Registry ID: 2024-517771-21-00
Title of the Study : Effect of Remote Ischemic Preconditioning in Septic Patients on Cell Cycle Arrest Biomarkers – the RIPC-ICU Randomized Clinical Trial
Synopsis: Acute kidney injury is a well-recognized complication in critically ill patients. Up to date there is no clinically established method to reduce the incidence or the severity of acute kidney injury.
Remote ischemic preconditioning (RIPC) will be induced by three cycles of upper limb ischemia.
The aim of the study is to reduce the incidence of AKI by implementing remote ischemic preconditioning (identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7(IGFBP7)
Publications:
Contact Person: Univ.-Prof. Dr. med. Alexander Zarbock (Hauptprüfer), Univ.-Prof. Dr. med. Melanie Meersch-Dini
Registry ID: NCT05830669
Title of the Study : BigpAK-2 Trial
Synopsis: The BigpAK-2 trial investigated whether a biomarker-guided preventive care strategy based on KDIGO recommendations can reduce the incidence of moderate or severe acute kidney injury (AKI) in high-risk patients undergoing major surgery. AKI is a frequent postoperative complication associated with increased morbidity, mortality, prolonged hospitalization, and higher healthcare costs. The study enrolled adult surgical patients identified as being at elevated risk for AKI through clinical risk factors and elevated urinary stress biomarkers ([TIMP-2]*[IGFBP7]). Participants were randomized to receive either a structured nephroprotective care strategy or standard care. The primary endpoint was the occurrence of moderate or severe AKI within 72 hours after surgery. The results provide important evidence regarding the effectiveness of targeted postoperative kidney-protection strategies and may influence future perioperative management guidelines for high-risk surgical patients.
Publications:
Zarbock A, Ostermann M, Forni L, Bode C, Wild L, Putensen C, Roux DP, Martín EE, Arndt C, Rahmel T, de Rosa S, Monard C, Schneider AG, Glass A, Jung-König M, Romagnoli S, Gossage J, Lumlertgul N, Haaker JG, Ripollés-Melchor J, Spadaro S, Siniscalchi A, Futier E, Aupetitgendre L, Bhathal IR, Álvarez RG, Bernard A, Rosenberger P, Wempe C, Sadjadi M, Meersch M, Fischhuber K, Bellomo R, Kellum JA, von Groote T; BigpAK-2 Study Group. A preventive care strategy to reduce moderate or severe acute kidney injury after major surgery (BigpAK-2): a multinational, randomised clinical trial. Lancet. 2025 Dec 13;406(10521):2782–2791. doi: 10.1016/S0140-6736(25)01717-9.
von Groote T, Meersch M, Romagnoli S, Ostermann M, Ripollés-Melchor J, Schneider AG, Vandenberghe W, Monard C, De Rosa S, Cattin L, Rahmel T, Adamzik M, Parise D, Candela-Toha A, Haaker JG, Göbel U, Bernard A, Lumlertgul N, Fernández-Valdes-Bango P, Romero Bhathal I, Suarez-de-la-Rica A, Larmann J, Villa G, Spadaro S, Wulf H, Arndt C, Putensen C, García-Álvarez R, Brandenburger T, Siniscalchi A, Ellerkmann R, Espeter F, Porschen C, Sadjadi M, Saadat-Gilani K, Weiss R, Gerss J, Kellum J, Zarbock A; BigpAK-2 Investigators. Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial. BMJ Open. 2023 Mar 27;13(3):e070240. doi: 10.1136/bmjopen-2022-070240.
von Groote T, Danzer MF, Meersch M, Zarbock A, Gerß J; BigpAK-2 Study Group. Statistical analysis plan for the biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2) study: An international randomised controlled multicentre trial. Crit Care Resusc. 2024 Jun 21;26(2):80–86. doi: 10.1016/j.ccrj.2024.03.001. Erratum in: Crit Care Resusc. 2024 Sep 12;26(3):223. doi: 10.1016/j.ccrj.2024.09.001.
Study Start and End:
Enrollment period: January 2022 to September 2024
Follow-up completed in 2024
Primary results published in 2025
Contact Persons: Univ.-Prof. Dr. med. Alexander Zarbock (Hauptprüfer), Dr. med. Thilo von Groote
Registry ID: NCT04600128
Title of the Study: Epidemiology of surgery associated acute kidney injury (EPIS-AKI)
Synopsis: EPIS-AKI is an international, prospective, multicenter observational cohort study involving 10,568 patients from 30 countries. The study focuses on acute kidney injury (AKI)—a serious complication with an increasing incidence that places a significant burden on healthcare systems worldwide. However, previous analyses of AKI incidence have been limited by inconsistent definitions and incomplete data, even though accurate knowledge of incidence and risk factors is essential for prevention, health policy, and further studies. The aim of the study is to determine the incidence of AKI within 72 hours after major surgical procedures using the current KDIGO consensus definition (serum creatinine and urine output) and to identify pre- and intraoperative risk factors. The study included all adult surgical patients whose surgery lasted more than two hours and who were subsequently admitted to a monitoring or intensive care unit. The results show that approximately one in five patients develops postoperative AKI (PO-AKI), with increasing severity associated with a higher incidence of adverse events. In addition, one in ten patients developed acute kidney disease (AKD) more than seven days after surgery—usually without prior postoperative acute kidney injury (PO-AKI). Nevertheless, PO-AKI within 72 hours proved to be an independent, strong predictor of subsequent AKD. With these data, EPIS-AKI provides multidisciplinary insights into the incidence of postoperative AKI and its risk factors. The results support preventive and health policy decisions, shed light on the transition from acute kidney injury to overt kidney disease, and form an important basis for planning further clinical trials.
Publications:
Zarbock A, Weiss R, Albert F, Rutledge K, Kellum JA, Bellomo R, Grigoryev E, Candela-Toha AM, Demir ZA, Legros V, Rosenberger P, Galán Menéndez P, Garcia Alvarez M, Peng K, Léger M, Khalel W, Orhan-Sungur M, Meersch M; EPIS-AKI Investigators. Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study. Intensive Care Med. 2023 Dec;49(12):1441-1455. doi: 10.1007/s00134-023-07169-7. Epub 2023 Jul 28. PMID: 37505258; PMCID: PMC10709241.
Meersch M, Weiss R, Strauß C, Albert F, Booke H, Forni L, Pittet JF, Kellum JA, Rosner M, Mehta R, Bellomo R, Rosenberger P, Zarbock A; EPIS-AKI Investigators. Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial. Intensive Care Med. 2024 Feb;50(2):247-257. doi: 10.1007/s00134-023-07314-2. Epub 2024 Jan 29. PMID: 38285051; PMCID: PMC10907445.
Weiss R, Saadat-Gilani K, Kerschke L, Wempe C, Meersch M, Zarbock A; EPIS-AKI Investigators. EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): study protocol for a multicentre, observational trial. BMJ Open. 2021 Dec 30;11(12):e055705. doi: 10.1136/bmjopen-2021-055705. PMID: 35588372; PMCID: PMC8718477.
Study Start and End:
06/2020 – 03/2022
Contact Persons: Univ.-Prof. Dr. med. Alexander Zarbock (Hauptprüfer), Priv.-Doz. Dr. med. Raphael Weiss
Registry ID: NCT04165369
Title of the Study: Biomarker-Guided Implementation of Angiotensin II to reduce the Occurrence of Kidney Damage after Cardiac Surgery (Aided-Trial)
Synopsis: Vasoplegia is a form of distributive shock characterized by low arterial pressure and reduced systemic vascular resistance; it occurs in 5–25% of cardiac surgery patients. It is associated with an increased risk of organ failure, particularly the development of acute kidney injury (AKI). Previous observations have shown that cardiac surgery leads to dysregulation of the renin-angiotensin-aldosterone system (RAAS) and that elevated renin levels are associated with cardiovascular instability and an increased rate of AKI. These findings could therefore help identify high-risk patients who would benefit from intervention with angiotensin II (AT-II). Postoperative AKI is a serious complication with an increasing incidence, the prevention of which has so far been largely unsuccessful—mostly because interventions did not begin until after functional loss had already occurred. The AIDED study takes a new approach: through the use of biomarkers, renal stress can be detected early and treated on an individualized basis before permanent damage occurs. Although norepinephrine is currently considered the first-line treatment for vasoplegia, all catecholamines are associated with side effects such as myocardial ischemia and arrhythmias. AT-II could represent a gentler alternative in this context, although data on its benefits in patients at high risk for AKI are currently lacking. The study included patients at high risk for AKI following cardiac surgery with cardiopulmonary bypass (CPB), identified by hyperreninemia (Δ-renin ≥ 3.7 µU/ml 4 hours after the end of CPB), and randomly assigned in a double-blind manner to either the AT-II or placebo arm. The results of this pilot study show that the 12-hour administration of AT-II did not lead to increased renal stress. Patients in the AT-II group also required less fluid and lower doses of vasopressors; the shorter length of stay in the intensive care unit and the lower rate of adverse events further support the safety of this approach. Overall, the results support further research into AT-II as a vasopressor in a selected group of patients with hyperreninemia, with the aim of specifically reducing cellular stress on the kidneys.
Publications:
Study Start and End: 06/2020 – 03/2022
Contact Persons: Univ.-Prof. Dr. med. Alexander Zarbock
Registry ID: NCT05199493
Funded by the DFG (Grant No.: ZA 428/21-1, Project No.: 458888477)
Participation in the study
If you are interested in participating in a study or have any questions about the studies, please feel free to contact Prof. Alexander Zarbock.