What side effects are associated with this type of intervention?

Common treatments for cardiovascular risk that target inflammation, such as anti-inflammatory agents and biologics like those targeting the IL-6 pathway, can have several side effects. These may include increased risk of infections due to immune suppression, injection site reactions (e.g., erythema, pain, or bruising), and potential hypersensitivity reactions such as rash, pruritus, and urticaria. Serious adverse events, although less common, can include severe infections, cardiovascular events like myocardial infarction, and neurocognitive symptoms. It is important for patients to discuss these potential risks with their healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments targeting the interleukin-6 (IL-6) pathway for various inflammatory conditions, which may have implications for cardiovascular risk. One notable example is tocilizumab, an IL-6 receptor antagonist, approved for conditions like rheumatoid arthritis and giant cell arteritis. While not specifically approved for cardiovascular risk reduction, its anti-inflammatory properties are relevant. Other anti-inflammatory agents, such as TNF-alpha inhibitors (e.g., adalimumab, etanercept), have shown benefits in reducing cardiovascular events in patients with inflammatory diseases like psoriasis and rheumatoid arthritis. These treatments highlight the potential of targeting inflammatory pathways to manage cardiovascular risk.

What other types of research exist?

Promising novel alternatives to Ziltivekimab for cardiovascular risk patients include Canakinumab (an IL-1β inhibitor) and Colchicine (an anti-inflammatory agent). Both have shown potential in reducing cardiovascular events by targeting inflammation. Additionally, ongoing research into other IL-6 inhibitors and novel anti-inflammatory agents may provide further options.

← Back to Search

Monoclonal Antibodies

Ziltivekimab for Cardiovascular Disease (ZEUS Trial)

Phase 3

Recruiting

Research Sponsored by Novo Nordisk A/S

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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)

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.

Must not have

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 within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomisation (month 0) to 2 years (24 months

Awards & highlights

Pivotal Trial

Summary

This trial is testing whether ziltivekimab can lower the risk of heart attacks and strokes in people with heart disease, kidney disease, and inflammation. Participants will inject the medicine regularly. The study aims to see if reducing inflammation can help prevent serious heart problems.

Who is the study for?

This trial is for people with both cardiovascular disease and chronic kidney disease, who also have inflammation. They must have a certain level of kidney function or protein in their urine, signs of heart-related artery issues, or peripheral artery disease. Pregnant women or those planning pregnancy are excluded.

What is being tested?

The study tests if ziltivekimab can prevent heart attacks and strokes better than a placebo in patients with heart and kidney diseases plus inflammation. Participants will inject either the drug or placebo monthly for up to 4 years, with regular clinic visits and cardiovascular assessments.

What are the potential side effects?

As ziltivekimab is new and not yet approved, potential side effects aren't fully known but may include reactions at the injection site, allergic responses, or other unforeseen complications related to immune system changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My kidney tests show a high protein level in my urine but my kidneys are still functioning well.

Select...

You have a history of heart disease, such as a heart attack or blocked arteries, or a history of stroke or blocked arteries in the neck.

Select...

I have heart or blood vessel disease.

Select...

I have symptoms of poor blood flow in my legs due to narrowed or blocked arteries.

Select...

I have chronic kidney disease with specific test results.

Select...

I have heart, brain, or leg artery disease proven by tests or procedures.

Select...

My kidney function is reduced but not extremely low.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am scheduled for a procedure to improve blood flow to my heart or other areas.

Select...

I haven't had major surgery in the last 60 days and don't plan any soon.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomisation (month 0) to 2 years (24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomisation (month 0) to 2 years (24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomisation (month 0) to 2 years (24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

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

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

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

+17 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: ZiltivekimabExperimental Treatment2 Interventions

Participants will receive Ziltivekimab B or Ziltivekimab C subcutaneously once monthly for up to 4 years.

Group II: PlaceboPlacebo Group2 Interventions

Participants will receive either placebo (Ziltivekimab B) or placebo (Ziltivekimab C) subcutaneously once monthly for up to 4 years.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ziltivekimab B

2023

Completed Phase 1

~270

Ziltivekimab C

2023

Completed Phase 1

~270

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for cardiovascular risk often target inflammation, a key factor in the development of cardiovascular diseases. Anti-inflammatory agents like ziltivekimab, which target the interleukin-6 (IL-6) pathway, work by reducing inflammation and lowering levels of C-reactive protein (CRP), a marker associated with cardiovascular events. Statins, another common treatment, lower cholesterol levels and also have anti-inflammatory effects. By reducing inflammation and cholesterol, these treatments help prevent the progression of atherosclerosis and reduce the risk of heart attacks and strokes. This is crucial for cardiovascular risk patients as it directly addresses the underlying mechanisms that contribute to cardiovascular events, thereby improving outcomes and survival rates.

Rationale and design for the Asymptomatic Carotid Artery Plaque Study (ACAPS). The ACAPS Group.Associations Between Drug Treatments and the Risk of Aneurysmal Subarachnoid Hemorrhage: a Systematic Review and Meta-analysis.Intensive statin therapy in coronary artery disease: is lower cholesterol better and safe?