What is the mechanism of action of this treatment?

Complement inhibition, particularly targeting the C5 protein as seen with Ravulizumab IV, is a therapeutic strategy for cardiovascular disease that aims to reduce inflammation and tissue damage by blocking the complement system's activation. This prevents the formation of the membrane attack complex (C5b-9), which can cause cell lysis and contribute to inflammation in atherosclerotic lesions. For cardiovascular disease patients, this is crucial as excessive complement activation can worsen vascular inflammation and plaque instability, leading to serious events like myocardial infarction and stroke. By inhibiting the complement pathway, such treatments may help stabilize atherosclerotic plaques and reduce the risk of adverse cardiovascular events.

What side effects are associated with this type of intervention?

Common treatments for cardiovascular disease that involve complement inhibition, such as those targeting the C5 protein (e.g., eculizumab), can have side effects including increased risk of infections due to immune suppression, infusion-related reactions, and potential development of drug-neutralizing antibodies. Other cardiovascular treatments, such as PCSK9 inhibitors (e.g., alirocumab, evolocumab), may cause injection site reactions, hypersensitivity reactions, and, rarely, neurocognitive symptoms. These treatments generally do not cause muscle toxicity or elevated liver enzymes.

What prior FDA approvals exist?

FDA-approved treatments for cardiovascular disease that involve complement inhibition via C5 protein targeting include eculizumab, which is an anti-C5 monoclonal antibody. Eculizumab has been used successfully to treat conditions like thrombotic microangiopathy, which can have cardiovascular implications. Broadly, other FDA-approved treatments for cardiovascular disease include statins for cholesterol management, beta-blockers for hypertension and heart failure, and anticoagulants like warfarin and newer agents such as rivaroxaban for preventing thromboembolic events.

What other types of research exist?

Promising novel alternatives to Ravulizumab IV for cardiovascular disease patients include other complement inhibitors such as Eculizumab, which also targets the C5 protein. Additionally, emerging therapies like C1 inhibitors (e.g., Berinert) and C3 inhibitors (e.g., Pegcetacoplan) are being explored for their potential benefits in cardiovascular conditions. Ongoing research into these and other complement-targeting therapies may provide new options for treatment in 2024.

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Monoclonal Antibodies

Ravulizumab for Kidney Damage from Heart Surgery (ARTEMIS Trial)

Phase 3

Recruiting

Research Sponsored by Alexion Pharmaceuticals, Inc.

Eligibility Criteria Checklist

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

Must have

Participant weighs ≥ 30 kg

Known CKD for at least 90 days (CKD Stage 3A, 3B, or 4)

Must not have

Single-vessel CABG without valve surgery is planned

Off-pump surgery is planned (eg, surgery without CPB)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing whether a single dose of ravulizumab, given through an IV, can help reduce kidney damage in adults with chronic kidney disease who are having planned heart surgery. The medication works by reducing inflammation and protecting the kidneys. The goal is to see if it can lower the risk of kidney problems in the months following surgery.

Who is the study for?

This trial is for adults with chronic kidney disease (CKD stages 3A, 3B, or 4) who weigh at least 30 kg and are scheduled for non-emergency heart surgery using cardiopulmonary bypass. Candidates should not have used certain kidney treatments or had infections recently and must be willing to get vaccinated against N meningitidis if needed.

What is being tested?

The ARTEMIS study is testing whether a single dose of ravulizumab given intravenously can reduce the risk of acute kidney injury after heart surgery compared to a placebo. The focus is on seeing if this treatment helps avoid major adverse kidney events within 90 days post-surgery.

What are the potential side effects?

While specific side effects are not listed here, ravulizumab may cause reactions related to the immune system such as increased infection risk. Participants will also need vaccinations against N meningitidis due to potential immunosuppression.

Eligibility Criteria

Inclusion Criteria

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

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I weigh at least 30 kilograms.

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I have been diagnosed with moderate to severe kidney disease for at least 3 months.

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I am scheduled for heart surgery that may include bypass or valve repair.

Exclusion Criteria

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

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I am scheduled for a single-vessel bypass surgery without any valve procedures.

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My surgery is planned without using a heart-lung machine.

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I have received a solid organ or bone marrow transplant.

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I have not had a serious infection in the last 14 days.

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I have not used heart support devices or had severe heart issues in the last 3 days.

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I often get infections without any known cause.

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I am willing to get vaccinated against N meningitidis and take antibiotics if needed.

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I am expected to need emergency heart surgery soon.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2022 Phase 4 trial • 18 Patients • NCT04320602

33%

Fatigue

17%

Abdominal pain

17%

COVID-19

17%

SARS-CoV-2 test positive

17%

Cough

11%

Back pain

11%

Nasopharyngitis

11%

Non-cardiac chest pain

11%

Dyspnoea

Pain

Pain in extremity

Chest discomfort

Body temperature abnormal

Rash

Herpes zoster

Upper respiratory tract congestion

Arthralgia

Peripheral swelling

Influenza like illness

Pneumonia

Asthenia

Retinal haemorrhage

Headache

Haemoglobinuria

Neurodermatitis

Pyrexia

Skin lesion

Nephrolithiasis

Upper respiratory tract infection

Urinary tract infection

Constipation

Extravascular haemolysis

Haemoglobin decreased

Oropharyngeal pain

Nail ridging

Chromaturia

100%

80%

60%

40%

20%

Study treatment Arm

Ravulizumab

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: RavulizumabExperimental Treatment1 Intervention

Participants will receive a single weight-based dose of ravulizumab, via intravenous infusion, 1 to 7 days prior to surgery.

Group II: PlaceboPlacebo Group1 Intervention

Participants will receive a single weight-based dose of placebo via intravenous infusion, 1 to 7 days prior to surgery.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ravulizumab

2016

Completed Phase 4

~1090

0 / 11Eligibility 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

Complement inhibition, particularly targeting the C5 protein as seen with Ravulizumab IV, is a therapeutic strategy for cardiovascular disease that aims to reduce inflammation and tissue damage by blocking the complement system's activation. This prevents the formation of the membrane attack complex (C5b-9), which can cause cell lysis and contribute to inflammation in atherosclerotic lesions. For cardiovascular disease patients, this is crucial as excessive complement activation can worsen vascular inflammation and plaque instability, leading to serious events like myocardial infarction and stroke. By inhibiting the complement pathway, such treatments may help stabilize atherosclerotic plaques and reduce the risk of adverse cardiovascular events.

Complement receptors and regulatory proteins in human atherosclerotic lesions.The Human Platelet as an Innate Immune Cell: Interactions Between Activated Platelets and the Complement System.Progress and Trends in Complement Therapeutics.