Anakinra for Heart Attack Prevention of Heart Failure

(VA-ART4 Trial)

Recruiting at 1 trial location

Overseen By Antonio Abbate, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Must not be taking: Immunosuppressives, Corticosteroids

Disqualifiers: Pregnancy, Prior STEMI, Heart failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether anakinra, an anti-inflammatory medicine, can prevent heart failure after a heart attack by reducing inflammation in the heart muscle. This is crucial because heart attacks can lead to heart failure, a condition where the heart cannot pump blood effectively. Participants will receive either anakinra or a placebo (a substance with no active treatment) to compare effects. Individuals who recently experienced a heart attack with chest pain and underwent a procedure to restore blood flow might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapies or high-dose oral corticosteroids, you may not be eligible to participate.

Is there any evidence suggesting that anakinra is likely to be safe for humans?

Research has shown that anakinra, the treatment under study, has been used for other heart conditions. Studies have found that it can lower the risk of heart failure, a condition where the heart can't pump blood effectively. This is crucial for individuals who have experienced a heart attack.

Previous patients have generally tolerated anakinra well, indicating that most people do okay with it. Some studies even suggest it might reduce the chance of worsening heart failure or dying from heart problems.

While no treatment is without risk, the research so far is promising regarding anakinra's safety in supporting the heart after a heart attack. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Unlike the standard treatments for heart failure prevention after a heart attack, which typically include medications like beta-blockers and ACE inhibitors, anakinra stands out by targeting inflammation. Anakinra is unique because it blocks the interleukin-1 (IL-1) pathway, a key player in the body's inflammatory response, which is thought to contribute to heart failure progression. Researchers are excited about anakinra because it offers a novel approach that could potentially reduce heart failure risk more effectively by addressing inflammation directly, providing hope for improved outcomes in patients.

What evidence suggests that anakinra might be an effective treatment for heart failure prevention?

Research has shown that anakinra, which participants in this trial may receive, might help prevent heart failure after a heart attack by reducing inflammation. This medication blocks a protein called interleukin-1, which causes inflammation. Early results suggest that anakinra can improve heart function by lowering this inflammation. Some studies have found that targeting interleukin-1 can help with heart problems related to inflammation. However, more research is needed to fully understand its effectiveness in preventing heart failure after a heart attack. ^{1 3 4 6 7}

Who Is on the Research Team?

Benjamin Van Tassell, PharmD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

This trial is for adults over 21 who've had a recent heart attack and are receiving treatment to restore blood flow. They must not be pregnant, have severe psychiatric issues, limited English proficiency that affects understanding of the study, prior significant heart attacks or heart failure, allergies to anakinra or E. coli products, certain infections like COVID-19 or chronic diseases like hepatitis B/C and HIV/AIDS.

Inclusion Criteria

Your ECG shows a specific type of heart abnormality called "ST segment elevation" in more than one area of your heart.

I have undergone or am planned to undergo a procedure to restore blood flow to my heart.

I am older than 21 years.

Exclusion Criteria

My chest pain lasted more than 12 hours before my heart artery procedure.

Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent from complying with study instructions

My heart procedure to improve blood flow didn't work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anakinra or placebo injections for 2 weeks

2 weeks

Daily injections, initially in-hospital, then at home

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Regular monitoring visits

Long-term follow-up

Participants are monitored for heart failure development over the course of 1 year

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Anakinra
• Placebo

Trial Overview The study is testing if Anakinra (an anti-inflammatory medicine) can reduce inflammation after a heart attack to prevent future heart weakening. Participants will either receive Anakinra or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: anakinra Experimental Treatment 1 Intervention

Group II: placebo Placebo Group 1 Intervention

Anakinra is already approved in European Union, United States for the following indications:

Approved in European Union as Kineret for:

• Rheumatoid arthritis
• Cryopyrin-associated periodic syndromes
• Deficiency of interleukin-1 receptor antagonist
• COVID-19

Approved in United States as Kineret for:

• Rheumatoid arthritis
• Deficiency of interleukin-1 receptor antagonist
• Neonatal-onset multisystem inflammatory disease (NOMID)
• COVID-19

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

In a pooled analysis of 40 patients with stable STEMI, treatment with anakinra, an IL-1 receptor antagonist, showed a neutral effect on recurrent ischemic events like death and heart attacks, with a hazard ratio of 1.08, indicating no significant benefit or harm.

However, anakinra was associated with a significant reduction in the risk of new-onset heart failure, with a hazard ratio of 0.16, suggesting it may help prevent heart failure in the long term after a heart attack.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies). Abbate, A., Kontos, MC., Abouzaki, NA., et al.[2022]

A phase II clinical trial is underway to evaluate the efficacy of anakinra, an IL-1 receptor antagonist, in improving peak oxygen consumption in 102 patients with acute decompensated heart failure and systemic inflammation over 24 weeks.

The trial aims to provide insights into how anakinra affects not only exercise capacity but also other heart function parameters and quality of life, potentially offering a novel treatment strategy for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study. Van Tassell, B., Mihalick, V., Thomas, G., et al.[2023]

Anakinra, an interleukin-1 blocker, significantly reduces systemic inflammation and the incidence of heart failure events in patients with STEMI, regardless of how quickly it is administered after reperfusion, as shown in a study of 139 patients.

The treatment was effective in both groups analyzed based on the timing of administration, demonstrating a reduction in C-reactive protein levels and a lower combined rate of death or new onset heart failure, indicating its efficacy in managing acute inflammatory responses in heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction. Del Buono, MG., Damonte, JI., Moroni, F., et al.[2023]

In a study of 139 patients with STEMI, elevated C-reactive protein (CRP) levels were strongly associated with higher rates of heart failure hospitalization or death, indicating that CRP can be a useful predictor of outcomes in these patients.

Treatment with anakinra significantly reduced CRP levels and was effective in preventing death or heart failure hospitalization, particularly in patients with high systemic inflammation, highlighting its potential as a therapeutic intervention in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of C-reactive protein levels and role of anakinra in patients with ST-elevation myocardial infarction. Moroni, F., Corna, G., Del Buono, MG., et al.[2023]

Anakinra (Kineret) is an effective treatment for rheumatoid arthritis that works by blocking the inflammatory effects of interleukin-1, but it requires daily self-injections due to its short half-life.

While Kineret is generally safe and well tolerated, it can cause injection-site reactions, which are common and may require management strategies to improve patient comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations. Kaiser, C., Knight, A., Nordström, D., et al.[2022]

In a study of 139 STEMI patients, women had higher baseline levels of hsCRP compared to men, indicating greater systemic inflammation, but both sexes showed similar responses to anakinra treatment.

Anakinra treatment resulted in lower hsCRP levels and a reduced incidence of new-onset heart failure or death compared to placebo in both men and women, suggesting its efficacy in managing inflammation after STEMI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to interleukin-1 blockade with anakinra in women and men with ST-segment elevation myocardial infarction. Corna, G., Golino, M., Talasaz, AH., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9844326/

Anakinra in Heart Failure: A Systematic Review and Meta- ... There is limited evidence on the efficacy of anakinra in improving outcomes of heart failure with reduced ejection fraction. Anakinra is an ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05177822

Study Details | NCT05177822 | Interleukin-1 Blockade in ... The researchers believe that the reaction of the heart muscle to injury (inflammation) during a heart attack may be contributing to the risk of heart failure.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5699505/

Results from the REcently Decompensated Heart failure ... Targeting Interleukin-1 in Heart Failure and Inflammatory Heart Disease. Curr Heart Fail Rep. 2015;12:33–41. doi: 10.1007/s11897-014-0231-7. [DOI] [PubMed] ...

4. jacc.org jacc.org/doi/10.1016/j.jchf.2024.07.018

Reply: Beyond Remodeling: Interleukin-1 Blockade as a ... Interleukin-1 blockade with anakinra and heart failure following ST-segment elevation myocardial infarction: results from a pooled analysis of the VCUART ...

5. withpower.com withpower.com/trial/phase-2-infarction-2022-1d3cc

Anakinra for Heart Attack Prevention of Heart Failure The researchers believe that the reaction of the heart muscle to injury (inflammation) during a heart attack may be contributing to the risk of heart failure.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9366639/

Interleukin-1 blockade with anakinra and heart failure ... ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure ( ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0021915025013413

Early Anti-inflammatory Therapy in Acute Myocardial ... Colchicine reduced MACE and ischemic events, while anakinra lowered the risk of heart failure. •. Clinical benefits were confined to treatments ...