Anakinra for Heart Attack Prevention of Heart Failure

(VA-ART4 Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Benjamin Van Tassell, PharmD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Virginia Commonwealth University

Must not be taking: Immunosuppressives, Corticosteroids

Disqualifiers: Pregnancy, Prior STEMI, Heart failure, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Patients who have a heart attack are at high risk for future development of heart failure ('weakening of the heart'). 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. The current study will test the ability of an anti-inflammatory medicine (anakinra) to block the inflammation in the body during and after a heart attack.

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.

What data supports the effectiveness of the drug Anakinra for preventing heart failure after a heart attack?

Research shows that Anakinra, a drug that blocks a protein called interleukin-1, can reduce inflammation and prevent heart failure in patients who have had a heart attack. Studies found that patients treated with Anakinra had fewer heart failure events compared to those who received a placebo. ^{1 2 3 4 5}

How is the drug anakinra unique in preventing heart failure after a heart attack?

Anakinra is unique because it works by blocking interleukin-1 (IL-1), a protein that causes inflammation, which helps reduce inflammation and prevent heart failure after a heart attack. Unlike other treatments, it is administered through daily injections and specifically targets the inflammatory response, which is a novel approach for heart attack patients. ^{1 2 3 4 6}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Anakinra (Interleukin-1 Blocker)
• Placebo (Other)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Virginia Charlottesville, VA

Virginia Commonwealth University Richmond, VA

Who Is Running the Clinical Trial?

Virginia Commonwealth University Lead Sponsor

National Institute on Aging (NIA) Collaborator

University of Virginia Collaborator

References

1. United States 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). [2022] Two pilot studies of interleukin-1 (IL-1) blockade in ST-segment elevation myocardial infarction (STEMI) showed blunted acute inflammatory response and overall favorable outcomes at 3 months follow-up. We hereby present a patient-level pooled analysis with extended follow-up of 40 patients with clinically stable STEMI randomized to anakinra, a recombinant IL-1 receptor antagonist, 100 mg/day for 14 days or placebo in a double-blinded fashion. End points included death, cardiac death, recurrent acute myocardial infarction (AMI), stroke, unstable angina, and symptomatic heart failure. Median follow-up was 28 (interquartile range 3 to 38) months. Sixteen patients (40%) had a total of 22 adverse cardiovascular events: 1 cardiac death, 4 recurrent AMI, 5 episodes of unstable angina pectoris requiring hospitalization and/or urgent revascularization, and 11 new diagnoses of heart failure. Treatment with anakinra was associated with a hazard ratio of 1.08 (95% confidence interval 0.31 to 3.74, p = 0.90) for the combined end point of death, recurrent AMI, unstable angina pectoris, or stroke and a hazard ratio of 0.16 (95% confidence interval 0.03 to 0.76, p = 0.008) for death or heart failure. In conclusion, IL-1 blockade with anakinra for 2 weeks appears, therefore, to have a neutral effect on recurrent ischemic events, whereas it may prevent new-onset heart failure long term after STEMI.

2. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of C-reactive protein levels and role of anakinra in patients with ST-elevation myocardial infarction. [2023] Interleukin-1 blockade with anakinra reduces C-reactive protein (CRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). The effectiveness of anakinra according to the degree of systemic inflammation in STEMI has not been addressed.

3. England 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. [2023] Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF.

4. Italy pubmed.ncbi.nlm.nih.gov

Response to interleukin-1 blockade with anakinra in women and men with ST-segment elevation myocardial infarction. [2023] Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra.

5. United States pubmed.ncbi.nlm.nih.gov

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction. [2023] Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups base6d on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 (182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 minutes (222.6 [103.9-325.2] vs. 78.4 [44.3-131.2], P < 0.001) and those with time from PCI to treatment ≥271 minute (235.2 [131.4-603.4] vs. 75.5 [38.9-171.9], P < 0.001) (P > 0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 minutes (5 [11%] vs. 9n[36%], log-rank χ 2 5.985, P = 0.014) as well as in patients with time from PCI to drug ≥271 minutes (2n[5%] vs. 7 [23%], log-rank χ 2 3.995, P = 0.046) (P > 0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. SIGNIFICANCE STATEMENT: In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, interleukin-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of interleukin-1 activity, and prevents heart failure events independent of time-to-treatment.

6. Germany pubmed.ncbi.nlm.nih.gov

Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations. [2022] Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret is self-administered by daily subcutaneous injections in patients with active RA. The mechanism of action of anakinra is to competitively inhibit the local inflammatory effects of IL-1. Kineret is generally safe and well tolerated and the only major treatment-related side effects that appear are skin reactions at the injection site. Due to the relatively short half-life of anakinra, daily injection of the drug is required. This, in combination with the comparably high rates of injection-site reactions (ISRs) associated with the drug, can become a problem for the patient. The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause. The objective is also to present some clinical experiences of how the ISRs can be managed.