A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS)
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 kidne...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Trials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13063-025-08895-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849341598968578048 |
|---|---|
| author | Marlies Ostermann David C. Corteville Kent Doi Jay L. Koyner Andre Lamy Gerry Li Christine M. Solinsky Pamela D. Winterberg William T. Smith Ravindra L. Mehta Patrick T. Murray Andrew D. Shaw Alexander Zarbock Daniel T. Engelman |
| author_facet | Marlies Ostermann David C. Corteville Kent Doi Jay L. Koyner Andre Lamy Gerry Li Christine M. Solinsky Pamela D. Winterberg William T. Smith Ravindra L. Mehta Patrick T. Murray Andrew D. Shaw Alexander Zarbock Daniel T. Engelman |
| author_sort | Marlies Ostermann |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-40f1ea284a1949638cdb2e708a4a3bc7 |
| institution | Kabale University |
| issn | 1745-6215 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj-art-40f1ea284a1949638cdb2e708a4a3bc72025-08-20T03:43:36ZengBMCTrials1745-62152025-05-0126111110.1186/s13063-025-08895-7A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS)Marlies Ostermann0David C. Corteville1Kent Doi2Jay L. Koyner3Andre Lamy4Gerry Li5Christine M. Solinsky6Pamela D. Winterberg7William T. Smith8Ravindra L. Mehta9Patrick T. Murray10Andrew D. Shaw11Alexander Zarbock12Daniel T. Engelman13Critical Care and Nephrology, NHS Foundation TrustDepartment of Cardiology, Rochester Regional HealthEmergency and Critical Care Medicine, The University of Tokyo HospitalSection of Nephrology, The University of ChicagoDivision of Cardiac Surgery and Population Health Research Institute, McMaster UniversityAlexion, AstraZeneca Rare DiseaseAlexion, AstraZeneca Rare DiseaseAlexion, AstraZeneca Rare DiseaseAlexion, AstraZeneca Rare DiseaseDepartment of Medicine, San Diego School of Medicine, University of CaliforniaUniversity College Dublin Clinical Research Centre, UCD School of MedicineDepartment of Intensive Care and Resuscitation, Cleveland ClinicDepartment of Anesthesiology, Intensive Care and Pain Medicine, University of MünsterHeart & Vascular Program Baystate Health, University of Massachusetts Chan Medical School-BaystateAbstract 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.https://doi.org/10.1186/s13063-025-08895-7Cardiac surgery-associated acute kidney injuryCardiopulmonary bypassChronic kidney diseaseComplement activationInterventional studyIschemia–reperfusion injury |
| spellingShingle | Marlies Ostermann David C. Corteville Kent Doi Jay L. Koyner Andre Lamy Gerry Li Christine M. Solinsky Pamela D. Winterberg William T. Smith Ravindra L. Mehta Patrick T. Murray Andrew D. Shaw Alexander Zarbock Daniel T. Engelman A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS) Trials Cardiac surgery-associated acute kidney injury Cardiopulmonary bypass Chronic kidney disease Complement activation Interventional study Ischemia–reperfusion injury |
| title | A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS) |
| title_full | A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS) |
| title_fullStr | A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS) |
| title_full_unstemmed | A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS) |
| title_short | A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS) |
| title_sort | phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery associated acute kidney injury and major adverse kidney events artemis |
| topic | Cardiac surgery-associated acute kidney injury Cardiopulmonary bypass Chronic kidney disease Complement activation Interventional study Ischemia–reperfusion injury |
| url | https://doi.org/10.1186/s13063-025-08895-7 |
| work_keys_str_mv | AT marliesostermann aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT davidccorteville aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT kentdoi aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT jaylkoyner aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT andrelamy aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT gerryli aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT christinemsolinsky aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT pameladwinterberg aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT williamtsmith aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT ravindralmehta aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT patricktmurray aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT andrewdshaw aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT alexanderzarbock aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT danieltengelman aphase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT marliesostermann phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT davidccorteville phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT kentdoi phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT jaylkoyner phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT andrelamy phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT gerryli phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT christinemsolinsky phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT pameladwinterberg phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT williamtsmith phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT ravindralmehta phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT patricktmurray phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT andrewdshaw phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT alexanderzarbock phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis AT danieltengelman phase3studyofravulizumabtoprotectpatientswithchronickidneydiseasefromcardiacsurgeryassociatedacutekidneyinjuryandmajoradversekidneyeventsartemis |