Abstract
Background
Cardiac procedures, particularly those requiring cardiopulmonary bypass (CPB), are associated with the development of cardiac surgery-associated acute kidney injury (CSA-AKI). Development of CSA-AKI occurs as a result of inflammation, uncontrolled complement activation, and kidney cell damage. In patients with preoperative renal impairment, such as those with chronic kidney disease (CKD), there is an increased risk of both CSA-AKI and poorer clinical outcomes. Currently, there are limited effective, targeted pharmacological interventions for the prevention or treatment of CSA-AKI, although emerging therapies are being investigated, particularly in patients with existing CKD. The ARTEMIS (RAvulizumab to PRotect PaTients with Chronic Kidney DisEase froM CSA-AKI and Subsequent Major Adverse Kidney Events) trial will assess the efficacy and safety of ravulizumab (a complement C5 inhibitor) in reducing the risk of major adverse kidney events (MAKE) in patients with preoperative CKD undergoing non-emergent cardiac surgery with CPB.
Methods
This trial is currently recruiting patients with CKD who have planned cardiac surgery requiring CPB including coronary artery bypass grafting, valve replacement or repair, or combined procedures. This is a phase 3, randomized, double-blind, placebo-controlled, global study assessing the efficacy and safety of a single preoperative dose of ravulizumab. These outcomes will be assessed using the occurrence of MAKE and its components, as well as the occurrence and severity of CSA-AKI throughout the study period.
Discussion
Complement activation is known to occur during and after cardiac procedures as a result of CPB and ischemia–reperfusion injury, leading to a cycle of cell damage and death. Therefore, it is hypothesized that preoperative administration of ravulizumab will provide immediate and complete complement inhibition, which will be sustained throughout the surgical period, preventing the uncontrolled complement activation associated with the development of CSA-AKI, thus minimizing poor outcomes for patients.
Trial registration
ClinicalTrials.gov NCT05746559. Registered on February 27, 2023.
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Details
1 NHS Foundation Trust, Critical Care and Nephrology, London, UK
2 Rochester Regional Health, Department of Cardiology, Rochester, USA (GRID:grid.417055.2) (ISNI:0000 0004 0382 5614)
3 The University of Tokyo Hospital, Emergency and Critical Care Medicine, Tokyo, Japan (GRID:grid.412708.8) (ISNI:0000 0004 1764 7572)
4 The University of Chicago, Section of Nephrology, Chicago, USA (GRID:grid.170205.1) (ISNI:0000 0004 1936 7822)
5 McMaster University, Division of Cardiac Surgery and Population Health Research Institute, Hamilton, Canada (GRID:grid.25073.33) (ISNI:0000 0004 1936 8227)
6 Alexion, AstraZeneca Rare Disease, Boston, USA (GRID:grid.25073.33)
7 Alexion, AstraZeneca Rare Disease, Boston, USA (GRID:grid.25073.33); Present Address: Vera Therapeutics, Brisbane, USA (GRID:grid.25073.33)
8 Alexion, AstraZeneca Rare Disease, Boston, USA (GRID:grid.25073.33); Present Address: Novartis, East Hanover, USA (GRID:grid.25073.33)
9 University of California, Department of Medicine, San Diego School of Medicine, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
10 UCD School of Medicine, University College Dublin Clinical Research Centre, Dublin, Ireland (GRID:grid.7886.1) (ISNI:0000 0001 0768 2743)
11 Cleveland Clinic, Department of Intensive Care and Resuscitation, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725); Present Address: Critical Care and ECMO Division of ABIOMED, J&J MedTech, Cleveland, USA (GRID:grid.239578.2)
12 University of Münster, Department of Anesthesiology, Intensive Care and Pain Medicine, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288)
13 University of Massachusetts Chan Medical School-Baystate, Heart & Vascular Program Baystate Health, Springfield, USA (GRID:grid.266683.f) (ISNI:0000 0001 2166 5835)