Anakinra for Heart Attack Prevention of Heart Failure (VA-ART4 Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Virginia Commonwealth University
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.
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop 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 idea that Anakinra for Heart Attack Prevention of Heart Failure is an effective drug?The available research shows that Anakinra, when used for heart attack patients, can help prevent heart failure. In one study, patients who received Anakinra had fewer cases of heart failure compared to those who received a placebo. Another study found that Anakinra reduced inflammation, which is linked to heart failure, and helped prevent heart failure events after a heart attack. These findings suggest that Anakinra is effective in reducing the risk of heart failure in heart attack patients.3891011
Is the drug Anakinra (Kineret) promising for preventing heart failure after a heart attack?Yes, Anakinra (Kineret) is promising for preventing heart failure after a heart attack. It helps reduce inflammation and lowers the risk of developing heart failure in the long term.2381011
What safety data exists for Anakinra in preventing heart failure after a heart attack?The provided research does not contain safety data for Anakinra or its related names (Kineret, Placebo, Control, Dummy Treatment) in the context of heart attack prevention of heart failure. The studies focus on cardiovascular safety of other drugs like liraglutide and DPP-4 inhibitors.14567
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
I have undergone or am planned to undergo a procedure to restore blood flow to my heart.
I am older than 21 years.
I had severe chest pain indicating a heart attack within the last 12 hours.
Exclusion Criteria
My heart procedure to improve blood flow didn't work.
I am not allergic to Kineret® or products made from E. coli.
I have had a severe heart attack or my heart pumps poorly.
I need or am planning to have urgent heart surgery.
I have advanced kidney disease or am on dialysis.
Treatment Details
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: anakinraExperimental Treatment1 Intervention
Group II: placeboPlacebo Group1 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 nearbySelect from list below to view details:
University of VirginiaCharlottesville, VA
Virginia Commonwealth UniversityRichmond, VA
Loading ...
Who is running the clinical trial?
Virginia Commonwealth UniversityLead Sponsor
National Institute on Aging (NIA)Collaborator
University of VirginiaCollaborator
References
Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies. [2022]We assessed the cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist, using existing clinical data. Patient-level results from all completed phase 2 and 3 studies from the liraglutide clinical development programme were pooled to determine rates of major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, stroke. MACE were identified by querying the study database using Medical Dictionary for Regulatory Activities (MedDRA) terms combined with serious adverse events recorded by study investigators. Broad, narrow, and custom groups of MedDRA queries were used. Candidate events from each query were independently adjudicated post hoc. In 15 studies (6638 patients; 4257 liraglutide treated), there were 114 patients with MACE identified using the broad MedDRA query. Of these, 44 were classified as serious adverse events and 39 were adjudicated as MACE. The incidence ratio for adjudicated broad/serious MACE associated with liraglutide was 0.73 (95% CI 0.38-1.41) versus all comparator drugs (metformin, glimepiride, rosiglitazone, insulin glargine, placebo), within cardiovascular safety limits defined by the United States Food & Drug Administration for diabetes therapies under current investigation.
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.
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.
Dipeptidyl peptidase-4 inhibitors and heart failure: Analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System. [2017]We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS).
Cardiovascular safety signals with dipeptidyl peptidase-4 inhibitors: A disproportionality analysis among high-risk patients. [2021]In 2008, the US Food and Drug Administration (FDA) issued Draft Guidance on investigating cardiovascular risk with oral diabetic drugs, including dipeptidyl peptidase-4 inhibitors (DPP-4i). In 2014, underpowered, post hoc analyses of clinical trials suggested an increased risk of heart failure with the use of these products. As such, we assessed disproportionate reporting of major adverse cardiac events (MACE) among reports for DPP-4i submitted to the FDA Adverse Event Reporting System (FAERS) from 2006 to 2015.
Signal Detection for Cardiovascular Adverse Events of DPP-4 Inhibitors Using the Korea Adverse Event Reporting System Database, 2008-2016. [2020]Cardiovascular adverse events (AEs) after use of dipeptidyl peptidase-4 (DPP4) inhibitors have been reported and suspected since the launch of DPP-4 inhibitors in 2006. However, few studies have investigated the association between cardiovascular AEs and DPP-4 inhibitors. The objective of this study is to detect the signals of cardiovascular AEs after use of DPP-4 inhibitors by analyzing the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD).
Dipeptidyl peptidase-4 inhibitors and cardiovascular events in patients with type 2 diabetes, without cardiovascular or renal disease. [2020]Cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) in patients without cardiovascular or renal disease, a majority of newly diagnosed patients with type 2 diabetes often excluded from clinical trials on this association, is poorly understood. Thus, we investigate the risk of major adverse cardiovascular events (MACE) associated with DPP-4i in low-risk patients with diabetes.
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.
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.
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.
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.