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BMJ Open. 2019 Jan 21;9(1):e024411. doi: 10.1136/bmjopen-2018-024411.

Regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH) trial: study protocol for a multicentre, randomised controlled trial.

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Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
Department of Anesthesiology and Critical Care Medicine, Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany.
Department of Intensive Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Nephrology, Charité University of Berlin, Berlin, Germany.
Department Intensive Care Medicine, University of Aachen, Aachen, Germany.
Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
Contributed equally



Acute kidney injury (AKI) is a well-recognised complication of critical illness which is of crucial importance for morbidity, mortality and health resource utilisation. Renal replacement therapy (RRT) inevitably entails an escalation of treatment complexity and increases costs for those patients with severe AKI. However, it is still not clear whether regional citrate anticoagulation or systemic heparin anticoagulation for continuous RRT (CRRT) is most appropriate. We hypothesise that, in contrast to systemic heparin anticoagulation, regional citrate anticoagulation for CRRT prolongs filter life span and improves overall survival in a 90-day follow-up period (coprimary endpoints).


We will conduct a prospective, randomised, multicentre, clinical trial including up to 1450 critically ill patients with AKI requiring CRRT. We suggest to investigate the effect of regional citrate anticoagulation for CRRT as compared with systemic heparin anticoagulation. The two coprimary outcomes are filter life span and overall survival in a 90-day follow-up period. Secondary outcomes are length of stay in the intensive care unit; length of hospitalisation; duration of CRRT; recovery of renal function at days 28, 60, 90 and 1 year; requirement for RRT after days 28, 60, 90 and 1 year; 28 days, 60 days, 90 days and 1-year all-cause mortality; major adverse kidney events at days 28, 60, 90 and 1 year; bleeding complications; transfusion requirements; infection rate and costs of RRT. Additionally, in an add-on study involving several of the participating centres, blood samples from recruited patients will be collected at different time points to analyse whether the anticoagulation strategy has an impact on immune response as evidenced by leucocyte recruitment and function.


The RICH trial has been approved by the Federal Institute for Drugs and Medical Devices, the leading Ethics Committee of the University of Münster and the corresponding Ethics Committee at each participating site.




acute renal failure; anticoagulation

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