Skip to main content
OpenTrials
Completed

NCT Number: NCT05021835

ZEUS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Cardiovascular Disease, Chronic Kidney Disease and Inflammation

This study is conducted to see if ziltivekimab reduces the risk of having cardiovascular events (for example heart attack and stroke) in people with cardiovascular disease, chronic kidney disease and inflammation.

Participants will either get ziltivekimab (active medicine) or placebo (a dummy medicine which has no effect on the body). This is known as the study medicine. Which treatment participants get is decided by chance. Participants chance of getting ziltivekimab or placebo is the same.

Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine doctors cannot prescribe.

Participants will get the study medicine in a pre filled syringe. Participants will need to use the pre filled syringe to inject the study medicine into a skinfold once-monthly.

The study is expected to last for up to 4 years. Participants will have up to 20 clinic visits. Participants will have blood and urine samples taken at most of the clinic visits.

Participants will have their heart examined using sound waves (echocardiography) and electrodes (electrocardiogram).

Women cannot take part if pregnant, breast-feeding or planning to get pregnant during the study period.

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CEMEDIC, CABA, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Chronic kidney disease defined by one of the below:
  • Estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 15 and below 60 mL/min/1.73 m^2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation)
  • Urinary albumin-to-creatinine ratio (UACR) >= 200 milligrams per gram (mg/g) and eGFR >= 60 mL/min/1.73 m2 (using the CKD-EPI creatinine equation)
  • Serum high-sensitivity C-reactive protein (hs-CRP) greater than or equal to 2 milligram per liter (mg/L)
  • Evidence of atherosclerotic cardiovascular disease (ASCVD) by one or more of the following:

a) Coronary heart disease defined as at least one of the following: i. Documented history of MI ii. Prior coronary revascularisation procedure iii. greater than or equal to 50% stenosis in major epicardial coronary artery documented by cardiac catheterisation or CT coronary angiography b) Cerebrovascular disease defined as at least one of the following: i. Prior stroke of atherosclerotic origin ii. Prior carotid artery revascularisation procedure iii. greater than or equal to 50% stenosis in carotid artery documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound.

c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an ankle-brachial index (ABI) below or equal to 0.90 at rest ii. Intermittent claudication with a greater than or equal to 50% stenosis in peripheral artery (excluding carotid) documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound iii. Prior peripheral artery (excluding carotid) revascularisation procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or osteomyelitis).

Exclusion criteria

  • Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
  • Myocardial infarction, stroke, hospitalisation for unstable angina pectoris, or transient ischaemic attack within 60 days prior to randomisation (visit 2).
  • Planned coronary, carotid or peripheral artery revascularisation known on the day of randomisation (visit 2).
  • Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2).

Treatment and study plan

Ziltivekimab B

Drug

Administered subcutaneously (s.c., under skin) once-monthly added to standard of care.

Ziltivekimab C

Drug

Administered subcutaneously (s.c., under skin) once-monthly added to standard of care.

Placebo (Ziltivekimab B)

Drug

Administered subcutaneously (s.c., under skin) once-monthly added to standard of care.

Placebo (Ziltivekimab C)

Drug

Administered subcutaneously (s.c., under skin) once-monthly added to standard of care.

Primary outcomes

  1. Time to first occurrence of 3-point Major Adverse Cardiovascular Event (MACE), a composite endpoint consisting of: Cardiovascular (CV) death, non-fatal Myocardial Infarction (MI) and non-fatal stroke

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months)

    Months

Secondary outcomes

  1. Time to first occurrence of expanded MACE, a composite endpoint consisting of: CV death, non-fatal MI, non-fatal stroke and hospitalisation for unstable angina pectoris requiring urgent coronary revascularisation

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months)

    Months

  2. Number of heart failure hospitalisations or urgent heart failure visits or CV deaths

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months)

    Count

  3. Time to first occurrence of a composite kidney endpoint consisting of: CV death, onset of persistent atleast 40 percent (%) reduction in eGFR (CKD-epidemiology collaboration [CKD-EPI]) compared with baseline, kidney failure

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months)

    Months

  4. Time to occurrence of all-cause mortality

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months)

    Months

  5. Time to first occurrence of each of the individual components of the expanded MACE endpoint and the kidney composite endpoint.

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    Months

  6. Time to first occurrence of MI (fatal and non-fatal).

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    Months

  7. Time to first occurrence of stroke (fatal and non-fatal).

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    Months

  8. Time to first occurrence of a composite MACE endpoint consisting of: all-cause mortality, non-fatal MI and non-fatal stroke

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    Months

  9. Time to first occurrence of a 4-component kidney endpoint consisting of: onset of persistent at least 40% reduction in eGFR (CKD-EPI) compared with baseline, kidney failure

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    Months

  10. Time to first occurrence of coronary revascularisation

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    Months

  11. Change in Urinary Abumin-to-Ceatinine ratio (UACR).

    Time frame: From randomisation (month 0) to 2 years (24 months).

    Percentage

  12. Change in eGFR (CKD-EPI))

    Time frame: From randomisation (month 0) to 2 years (24 months)

    mL/min/1.73 m^2

  13. Annual rate of change in eGFR (CKD-EPI) (total eGFR slope)

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    mL/min/1.73 m^2/ year

  14. Change in high-sensitivity C-reactive protein (hs-CRP)

    Time frame: From randomisation (month 0) to 2 years (24 months

    Percentage

  15. Change in N-terminal-pro-brain natriuretic peptide ( NT-pro-BNP)

    Time frame: From randomisation (month 0) to 2 years (24 months)

    Percentage

  16. Change in left ventricular ejection fraction (LVEF)

    Time frame: From randomisation (month 0) to 2 years (24 months)

    Percentage

  17. Number of events of atrial fibrillation

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    Count

  18. Change in haemoglobin

    Time frame: From randomisation (month 0) to 2 years (24 months)

    Grams per deciliter (g/dL)

  19. Number of hospitalisations with infection as primary cause or death due to infection.

    Time frame: From randomisation (month 0) to end-of-study (up to 48 months).

    Count

  20. Change in Short Form 36 (SF-36) Physical Component Score (PCS)

    Time frame: From randomisation (month 0) to 2 years (24 months)

    Score on scale

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

ZEUS - Effects of Ziltivekimab Versus Placebo on Cardiovascular Outcomes in Participants With Established Atherosclerotic Cardiovascular Disease, Chronic Kidney Disease and Systemic Inflammation

Acronym: ZEUS

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Aug 26, 2021
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.