ARTEMIS: Ravulizumab to Protect Patients With CKD From CSA-AKI and MAKE

Study Overview
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Brief Summary
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The primary objective of this study is to assess the efficacy of a single dose of ravulizumab IV compared with placebo in reducing the risk of the clinical consequences of AKI (MAKE) at 90 days in adult participants with CKD who undergo non-emergent cardiac surgery with CPB.

Official Title
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ARTEMIS: RAvulizumab to PRotect PaTients With Chronic Kidney DisEase (CKD) froM Cardiac Surgery Associated Acute Kidney Injury (CSA-AKI) and Subsequent Major Adverse Kidney Events (MAKE): A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study

Conditions
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Chronic Kidney Disease, CKD, Cardiac Disease, Cardiopulmonary Bypass

Intervention / Treatment
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* Drug: Placebo
* Drug: Ravulizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant weighs ≥ 30 kg Planned non-emergent sternotomy with CPB procedure for the following surgeries: Multi-vessel CABG Valve replacement or repair; ascending aorta surgery permitted if combined with aortic valve replacement/repair Combined CABG and valve surgery; inclusion of single-vessel CABG when combined with valve replacement/repair is permitted Known CKD for at least 90 days (CKD Stage 3A, 3B, or 4) Exclusion Criteria: Emergency or salvage cardiac surgery is expected at screening or randomization, as assessed by the Investigator. Single-vessel CABG without valve surgery is planned. Off-pump surgery is planned (eg, surgery without CPB). Recipient of a solid organ or bone marrow transplantation. Cardiogenic shock, hemodynamic instability, use of intra-aortic balloon pump, extracorporeal membrane oxygenation, or left ventricular assist device within 72 hours of randomization. Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization. History of unexplained, recurrent infection. Any use of KRT or presence of AKI within 30 days of randomization Use of any complement inhibitors, or plasmapheresis or plasma exchange within the year prior to Screening, or planned use during the course of the study. Participant is not willing to be vaccinated against N meningitidis or is unwilling to receive prophylactic treatment with appropriate antibiotics, if needed History of or unresolved N meningitidis infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive a single weight-based dose of placebo via intravenous infusion, 1 to 7 days prior to surgery. | Drug: Placebo<br>* Participants will receive a single weight-based dose of placebo via intravenous infusion.<br>|
| Experimental: Ravulizumab<br>Participants will receive a single weight-based dose of ravulizumab, via intravenous infusion, 1 to 7 days prior to surgery. | Drug: Ravulizumab<br>* Participants will receive a single weight-based dose of ravulizumab via intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Major Adverse Kidney Events (MAKE) (Based on serum Cystatin C [sCysC]) at Day 90 Post Cardiopulmonary Bypass (CPB) |  | Day 90 post-CPB | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Free From Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) at Day 90 Post CPB |  | Day 90 post-CPB | 
| Number of Participants Free From Severe CSA-AKI (Kidney Disease: Improving Global Outcomes [KDIGO] Stage 2 or 3) Based on Highest Observed Serum Creatinine (sCr) Within 7 Days Post CPB |  | Baseline through Day 7 post-CPB | 
| Number of Participants Free From Any Severe Acute Kidney Injury (AKI) (Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease [RIFLE] Injury or Failure Criteria) Based on Highest Observed sCr Within Day 30 Post CPB |  | Baseline through Day 30 post-CPB | 
| Number of Participants Free From Any Severe AKI (KDIGO Stage 2 or 3) Based on Highest Observed sCr Within Day 30 Post CPB |  | Baseline through Day 30 post-CPB | 
| Number of Participants Free From Any RIFLE Failure Criteria Based on Highest Observed sCr Within Day 30 Post CPB |  | Baseline through Day 30 post-CPB | 
| Number of Participants Who Experienced MAKE at Days 30, 60, and 90 (Excluding MAKE90 Based on sCysC) Post CPB |  | Days 30, 60, and 90 post-CPB | 
| Number of Participants Who Died or had Kidney Replacement Therapy (KRT) at Days 30, 60, and 90 Post CPB |  | Days 30, 60, and 90 post-CPB | 
| Number of Participants with the Highest CSA-AKI Stage Within 3 and 7 Days Post CPB |  | Baseline through Day 3 and Day 7 post-CPB | 
| Number of Participants Free From CSA-AKI at Days 15, 30, and 60 Post CPB |  | Days 15, 30, and 60 post-CPB | 
| Number of Participants Free From Any AKI at Days 3, 7, 15, 30, 60, and 90 Post CPB |  | Days 3, 7, 15, 30, 60, and 90 post-CPB | 
| Number of Participants with AKI Progression on Days 15, 30, 60, and 90 Post CPB for Those Experiencing CSA-AKI Within 7 Days Post CPB |  | Days 15, 30, 60, and 90 post-CPB | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease, CKD, Cardiac Disease, cardiopulmonary bypass