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

Abstract

Introduction: 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).

Methods and analysis: 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.

Ethics and dissemination: 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.

Trial registration number: NCT02669589.

Keywords: acute renal failure; anticoagulation.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Trial workflow. The research coordinators will screen patients in all participating ICUs for eligibility on a daily basis. Prior to enrolment, it is assured that fluid status is optimised if necessary. Patients not yet fulfilling the inclusion criteria will be rescreened each day. Patients fulfilling one of the exclusion criteria will be excluded and not rescreened. Before initiating RRT, blood and urine samples will be collected and different variables will be documented. CRRT will be started as soon as possible in patients with a clinical indication for RRT or within 24 hours after diagnosing severe AKI (KDIGO stage 3). Patients in the ‘regional citrate group’ receive regional citrate with a posthaemofilter ionised Ca++ level of 0.25–0.35 mmol/L as anticoagulant for CRRT. Patients in the ‘systemic heparin group’ receive systemic heparin with a target aPTT of 45–60 s as anticoagulant for CRRT. Laboratory tests will be analysed and variables relevant for the assessment of illness severity will be recorded during ICU stay on days 1–14, day 21, day 28. Follow-up will be performed after days 60, 90 and 1 year. AKI, acute kidney injury; aPTT, activated Partial Thromplastin Time; CKD, chronic kidney disease; CRRT, continuous renal replacement therapy; FiO2, fractional inspired oxygen; HIT, heparin-induced thrombocytopaenia; HUS, haemolytic uraemic syndrome; ICU, intensive care unit; INR, International Normalized Ratio; KDIGO, Kidney Disease: Improving Global Outcomes; KKS, Koordinierungszentrum für Klinische Studien (coordination center for clinical trials); PaO2, arterial oxygen tension; RRT, renal replacement therapy; TTP, thrombotic thrombocytopaenic purpura.