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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease; CKD; Cardiopulmonary Bypass; Cardiac Disease
• Intervention / Treatment: Drug: Placebo; Drug: Ravulizumab

• Study Type: Interventional
• Enrollment (Estimated): 736
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alexion Pharmaceuticals, Inc. (Sponsor); Phone Number: 1-855-752-2356; Email: clinicaltrials@alexion.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1110 AAF
    • Withdrawn
    • Research Site
  • Caba, Argentina, C1428DCO
    • Recruiting
    • Research Site
  • Ciudad Autónoma de Bs. As., Argentina, C1199ABB
    • Recruiting
    • Research Site
  • Cordoba, Argentina, X5016
    • Withdrawn
    • Research Site
  • Cordoba, Argentina, X5000 FAL
    • Withdrawn
    • Research Site
  • Corrientes, Argentina, W3400AMZ
    • Recruiting
    • Research Site
  • Córdoba, Argentina, X5016LIG
    • Not yet recruiting
    • Research Site
  • San Luis, Argentina, 5700
    • Recruiting
    • Research Site
  • Santa Fé, Argentina, S3000EOM
    • Recruiting
    • Research Site
• Australia
  • Brisbane, Australia, 4102
    • Recruiting
    • Research Site
  • Canberra, Australia, 2605
    • Recruiting
    • Research Site
  • Heidelberg, Australia, 3081
    • Withdrawn
    • Research Site
  • Monash, Australia
    • Recruiting
    • Research Site
  • Murdoch, Australia, 6150
    • Recruiting
    • Research Site
  • Southport, Australia, 4215
    • Recruiting
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• Brazil
  • Belo Horizonte, Brazil, 30150-221
    • Recruiting
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  • Campinas, Brazil, 13060-080
    • Recruiting
    • Research Site
  • Fortaleza, Brazil, 60430-375
    • Recruiting
    • Research Site
  • Porto Alegre, Brazil, 90620-001
    • Recruiting
    • Research Site
  • Ribeirão Preto, Brazil, 14051-140
    • Recruiting
    • Research Site
  • S.J. Do Rio Preto, Brazil, 15090-000
    • Recruiting
    • Research Site
  • Salvador, Brazil, 40301-155
    • Recruiting
    • Research Site
  • Sao Paulo, Brazil, 05403-000
    • Recruiting
    • Research Site
  • Sao Paulo, Brazil, 01321-001
    • Recruiting
    • Research Site
  • Sao Paulo, Brazil, 1323001
    • Recruiting
    • Research Site
  • São Paulo, Brazil, 04012-180
    • Recruiting
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Recruiting
      • Research Site
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L4
      • Recruiting
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  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Research Site
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Research Site
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
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  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Research Site
    • Montreal, Quebec, Canada, H2X 0C1
      • Recruiting
      • Research Site
    • Montréal, Quebec, Canada, H1T 1C8
      • Recruiting
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• China
  • Fuzhou, China, 350001
    • Not yet recruiting
    • Research Site
  • Gaozhou, China, 525232
    • Not yet recruiting
    • Research Site
  • Guangzhou, China, 510120
    • Recruiting
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  • Hangzhou, China, 310014
    • Not yet recruiting
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  • Hangzhou, China, 310030
    • Recruiting
    • Research Site
  • Ningbo, China, 315100
    • Recruiting
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  • Shanghai, China, 200032
    • Recruiting
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  • Shenzhen, China, 518036
    • Recruiting
    • Research Site
  • Shenzhen, China, 518053
    • Recruiting
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  • Tianjin, China, 300052
    • Recruiting
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  • Wuhan, China, 430071
    • Withdrawn
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  • Zhengzhou, China
    • Recruiting
    • Research Site
  • Zhengzhou, China, 450007
    • Recruiting
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• Germany
  • Dresden, Germany, 01307
    • Withdrawn
    • Research Site
  • Essen, Germany, 45147
    • Recruiting
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  • Frankfurt am Main, Germany, 60590
    • Recruiting
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  • Giessen, Germany, 35392
    • Recruiting
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  • Halle (Saale), Germany, 06120
    • Recruiting
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  • Heidelberg, Germany, 69120
    • Recruiting
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  • Jena, Germany, 07747
    • Recruiting
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  • Muenster, Germany, 48149
    • Withdrawn
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  • München, Germany, 81377
    • Recruiting
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  • Trier, Germany, 54292
    • Recruiting
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• Hong Kong
  • Hong Kong, Hong Kong
    • Not yet recruiting
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• India
  • Bangalore, India, 560092
    • Not yet recruiting
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  • Bangalore, India, 560069
    • Not yet recruiting
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  • Delhi, India, 110060
    • Not yet recruiting
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  • Gurgaon, India, 122001
    • Not yet recruiting
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  • Hyderabad, India, 500032
    • Not yet recruiting
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  • Mysuru, India, 570004
    • Not yet recruiting
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  • Secunderabad, India, 500003
    • Not yet recruiting
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• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Research Site
  • Haifa, Israel, 34362
    • Recruiting
    • Research Site
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Research Site
  • Ramat Gan, Israel, 52621
    • Withdrawn
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Recruiting
    • Research Site
  • Milan, Italy, 20138
    • Recruiting
    • Research Site
  • Milano, Italy, 20121
    • Withdrawn
    • Research Site
  • Napoli, Italy, 80131
    • Recruiting
    • Research Site
• Japan
  • Bunkyo-ku, Japan, 113-8431
    • Recruiting
    • Research Site
  • Chuo-ku, Japan, 104-8560
    • Recruiting
    • Research Site
  • Kamakura-shi, Japan, 247-8533
    • Recruiting
    • Research Site
  • Kawasaki-shi, Japan, 216-8511
    • Recruiting
    • Research Site
  • Minato-ku, Japan, 105-8470
    • Recruiting
    • Research Site
  • Okayama-shi, Japan, 700-0804
    • Recruiting
    • Research Site
  • Sagamihara-shi, Japan, 252-0375
    • Recruiting
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  • Suginami, Japan, 168-0065
    • Recruiting
    • Research Site
  • Urayasu, Japan, 279-0001
    • Recruiting
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• Korea, Republic of
  • Anyang-si, Korea, Republic of, 14068
    • Recruiting
    • Research Site
  • Busan, Korea, Republic of, 49241
    • Recruiting
    • Research Site
  • Daegu, Korea, Republic of, 42601
    • Recruiting
    • Research Site
  • Daegu, Korea, Republic of, 42472
    • Recruiting
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 02841
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 120-752
    • Recruiting
    • Research Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Research Site
  • Maastricht, Netherlands, 6229 HX
    • Not yet recruiting
    • Research Site
  • Rotterdam, Netherlands, 3015 GD
    • Not yet recruiting
    • Research Site
• Poland
  • Bielsko-Biała, Poland, 43-316
    • Recruiting
    • Research Site
  • Chrzanów, Poland, 32-500
    • Recruiting
    • Research Site
  • Grudziądz, Poland, 86-300
    • Not yet recruiting
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  • Katowice, Poland, 40-635
    • Not yet recruiting
    • Research Site
  • Kraków, Poland, 31-202
    • Not yet recruiting
    • Research Site
  • Lodz, Poland, 91-347
    • Recruiting
    • Research Site
  • Poznań, Poland, 60-355
    • Recruiting
    • Research Site
  • Szczecin, Poland, 70-111
    • Recruiting
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  • Tychy, Poland, 43-100
    • Recruiting
    • Research Site
  • Warszawa, Poland, 02-972
    • Not yet recruiting
    • Research Site
  • Łódź, Poland, 92-213
    • Recruiting
    • Research Site
• Spain
  • A Coruna, Spain, 15006
    • Recruiting
    • Research Site
  • Barcelona, Spain, 08036
    • Recruiting
    • Research Site
  • Barcelona, Spain, 8035
    • Recruiting
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  • Córdoba, Spain, 14004
    • Recruiting
    • Research Site
  • Madrid, Spain, 28040
    • Recruiting
    • Research Site
  • Madrid, Spain, 28041
    • Recruiting
    • Research Site
  • Majadahonda, Spain, 28250
    • Recruiting
    • Research Site
  • Navarra, Spain, 31190
    • Recruiting
    • Research Site
  • Santander, Spain, 39008
    • Withdrawn
    • Research Site
  • Sevilla, Spain, 41071
    • Recruiting
    • Research Site
  • Valencia, Spain, 46010
    • Recruiting
    • Research Site
  • Valladolid, Spain, 47003
    • Recruiting
    • Research Site
• Taiwan
  • Hualien City, Taiwan, 970473
    • Recruiting
    • Research Site
  • New Taipei, Taiwan, 220
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 40447
    • Recruiting
    • Research Site
  • Tainan City, Taiwan, 70403
    • Recruiting
    • Research Site
  • Taipei City, Taiwan, 11696
    • Recruiting
    • Research Site
• Turkey
  • Ankara, Turkey, 06800
    • Recruiting
    • Research Site
  • Istanbul, Turkey, 34093
    • Recruiting
    • Research Site
  • Istanbul, Turkey, 34303
    • Recruiting
    • Research Site
  • Istanbul, Turkey, 34846
    • Recruiting
    • Research Site
  • Istanbul, Turkey, 34668
    • Recruiting
    • Research Site
  • Istanbul, Turkey, 34349
    • Recruiting
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0AY
    • Recruiting
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  • Clydebank, United Kingdom, G81 4DY
    • Recruiting
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  • Edinburgh, United Kingdom, EH16 4SA
    • Recruiting
    • Research Site
  • London, United Kingdom, SW17 0QT
    • Recruiting
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  • London, United Kingdom, W12 0HS
    • Recruiting
    • Research Site
  • London, United Kingdom, SE1 9RT
    • Not yet recruiting
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  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Not yet recruiting
      • Research Site
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
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    • San Francisco, California, United States, 94121
      • Not yet recruiting
      • Research Site
    • Stanford, California, United States, 94305
      • Recruiting
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  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
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  • District of Columbia
    • Washington, District of Columbia, United States, 20037-2342
      • Withdrawn
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  • Florida
    • Gainesville, Florida, United States, 32610
      • Withdrawn
      • Research Site
    • Orlando, Florida, United States, 32804
      • Suspended
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • Research Site
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Withdrawn
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Withdrawn
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Research Site
    • Springfield, Massachusetts, United States, 01107
      • Not yet recruiting
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  • Michigan
    • Detroit, Michigan, United States, 48201
      • Not yet recruiting
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    • Detroit, Michigan, United States, 48202
      • Not yet recruiting
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  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Not yet recruiting
      • Research Site
    • Saint Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Withdrawn
      • Research Site
  • New Jersey
    • Haddon Heights, New Jersey, United States, 08035
      • Withdrawn
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  • New York
    • Rochester, New York, United States, 14621
      • Not yet recruiting
      • Research Site
    • Valhalla, New York, United States, 10595
      • Recruiting
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  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Withdrawn
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  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Recruiting
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  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Withdrawn
      • Research Site
    • Cleveland, Ohio, United States, 44126
      • Not yet recruiting
      • Research Site
    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
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  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Recruiting
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    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19141
      • Not yet recruiting
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  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
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  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
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    • Houston, Texas, United States, 77030
      • Recruiting
      • Research Site
    • Plano, Texas, United States, 75093
      • Withdrawn
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  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Not yet recruiting
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
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    • Richmond, Virginia, United States, 23298
      • Not yet recruiting
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  • Washington
    • Seattle, Washington, United States, 98195
      • Not yet recruiting
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    • Tacoma, Washington, United States, 98405
      • Recruiting
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  • Wisconsin
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2023
• Primary Completion (Estimated): May 17, 2026
• Study Completion (Estimated): May 17, 2026

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: February 16, 2023
• First Posted (Actual): February 27, 2023

Study Record Updates

• Last Update Posted (Estimated): May 15, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; CKD; cardiopulmonary bypass; Cardiac Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Ravulizumab
• Other Study ID Numbers: D928DC00001; ALXN1210-CSA-AKI-318 (Other Identifier: Alexion Pharmaceuticals, Inc.); 2022-501802-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No