Anakinra for Heart Failure

(AID-HEART Trial)

Overseen By Benjamin VanTassell

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Virginia Commonwealth University

Must be taking: Inotropes

Must not be taking: Immunosuppressives, Anti-inflammatories

Disqualifiers: Hypertension, Arrhythmias, Pulmonary disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Anakinra (also known as Kineret) for individuals with stage D heart failure. The goal is to determine if Anakinra can reduce the need for inotropes, which support the heart but may cause serious side effects. Suitable candidates for this trial have stage D heart failure, are on a stable dose of inotrope therapy (such as dobutamine or milrinone) for at least 28 days, have documented impaired heart function within the last year, and have maintained stable health over the past month without hospital visits. Participants must agree to follow the study's requirements, including self-administering the treatment and participating in an exercise plan. As a Phase 1 trial, the research focuses on understanding how Anakinra works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of inotrope therapy (like dobutamine or milrinone) for at least 28 days before joining. However, if you are taking immunosuppressive or anti-inflammatory drugs, you must stop them at least 14 days before starting the trial.

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

Research shows that anakinra, the treatment under study, is generally safe and well-tolerated. Studies have found that it can significantly lower levels of C-reactive protein (CRP), an indicator of inflammation in the body. In one study, patients who took anakinra experienced no major side effects over 4 to 12 weeks. Another study found that while anakinra was safe, it did not improve exercise ability in patients with heart failure after two weeks. Overall, these findings suggest that anakinra may be a safe option for patients with heart failure, but more research is needed to understand its effectiveness. ^{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, which typically include medications like beta-blockers, ACE inhibitors, and diuretics, Anakinra takes a novel approach by targeting inflammation. Anakinra is an interleukin-1 (IL-1) receptor antagonist, meaning it works by blocking the activity of a specific protein involved in the inflammatory process that can worsen heart failure. Researchers are excited about Anakinra because it offers a new mechanism of action that could complement existing therapies and potentially improve outcomes for patients who don't fully respond to current treatments.

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

Research shows that anakinra, which participants in this trial will receive, can help with heart failure. Studies indicate that anakinra significantly lowers levels of CRP, a protein that rises with inflammation and is often elevated in heart failure. Reducing CRP can improve heart health. Anakinra has also been linked to better heart function, with some patients experiencing improvements in how well their heart pumps. This suggests that anakinra might help manage symptoms and enhance heart function in people with severe heart failure. ^{1 2 3 6 7}

Who Is on the Research Team?

Azita Talasaz

Principal Investigator

Virginia Coomonwealth University

Are You a Good Fit for This Trial?

This trial is for adults over 21 with stage D heart failure who have been on a stable inotrope dose without hospitalization for the past month. They must be able to self-administer treatment and follow the protocol, with an ejection fraction <50% and C-reactive protein levels >2 mg/L. Excluded are those with chronic inflammation, pregnancy, neutropenia, significant comorbidities that affect study participation, recent or planned heart surgeries or devices, immunosuppressive drug use, active infections including certain viruses but not HCV with undetectable RNA, current malignancies except certain skin cancers or carcinoma in situ.

Inclusion Criteria

The patient is willing and able to comply with the protocol (i.e. self administration of the treatment, and exercise protocol)

Your blood test showed high C-reactive protein levels.

I am 21 or older and can sign a consent form.

Exclusion Criteria

I have advanced kidney disease or am on dialysis.

I do not have any serious health issues that could affect my participation in the study.

I do not have any active infections, including chronic diseases like HIV, but HCV is okay if undetectable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an IL-1 antagonist (anakinra) to evaluate its effects on inotrope sensitivity and exercise capacity

12 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anakinra

Trial Overview The AID-HEART trial tests Anakinra's effect on reducing the need for inotropes which increase cardiac output but carry risks like adverse cardiac remodeling and arrhythmias. The goal is to improve management of patients with end-stage heart failure by potentially lowering doses or duration of inotrope therapy.

How Is the Trial Designed?

Group I: Treatment arm Experimental Treatment 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+

Published Research Related to This Trial

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]

Anakinra, an interleukin 1 receptor antagonist, effectively reduces inflammation and is recommended as a third-line treatment for refractory recurrent pericarditis, according to the 2015 European Society of Cardiology guidelines.

Recent studies, including the AIRTRIP trial and the International Registry of Anakinra for Pericarditis, provide evidence supporting the safety and efficacy of anakinra in managing recurrent pericarditis, highlighting its clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anakinra in Recurrent Pericarditis: Current Evidence on Clinical Use, Effectiveness, and Safety. Correia, ETO., Dos Santos Barbetta, LM., de Almeida, JPCL., et al.[2021]

In a study of 13 patients with recurrent pericarditis resistant to standard treatments, all patients experienced significant symptom relief after receiving anakinra, with most achieving complete resolution within 2 to 5 days.

Anakinra allowed 84% of patients to discontinue other medications like glucocorticoids and nonsteroidal anti-inflammatory drugs, with only minor side effects reported, suggesting it could be a promising alternative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Anakinra for Management of Refractory Pericarditis. Jain, S., Thongprayoon, C., Espinosa, RE., et al.[2015]

The study successfully produced biologically active recombinant IL-1 receptor antagonist (rIL-1Ra) using a one-step purification method, which could lower production costs and time for this important therapeutic protein.

The rIL-1Ra demonstrated an 86% inhibition of IL-1β in treated cells, showing comparable efficacy to the standard drug Kineret®, which had a 96% inhibition rate, indicating that the new production method retains the therapeutic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Production and One-Step Purification of IL-1Ra in Escherichia coli and Evaluation of its IL-1 Antagonizing Efficacy. Adelnia, R., Shafiee, F.[2021]

Anakinra, an interleukin-1 receptor antagonist, shows promising efficacy for various dermatologic conditions, particularly hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome, based on a review of available studies and case reports.

With a relatively benign adverse effect profile, anakinra may be a valuable treatment option for patients with difficult-to-treat dermatologic diseases that do not respond to standard therapies, although more high-quality research is needed to better define its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-Label studies on anakinra in dermatology: a review. Tegtmeyer, K., Atassi, G., Zhao, J., et al.[2022]

In a study of 30 patients with acute decompensated heart failure (ADHF), treatment with anakinra significantly reduced inflammatory marker C-reactive protein (CRP) levels by 61% within 72 hours, compared to only a 6% reduction in the placebo group.

Anakinra was well tolerated by patients, suggesting it is a safe option for targeting inflammation in ADHF, but further research is needed to see if this reduction in inflammation leads to better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-1 Blockade in Acute Decompensated Heart Failure: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study. Van Tassell, BW., Abouzaki, NA., Oddi Erdle, C., et al.[2018]

In a study of 12 hospitalized patients with non-idiopathic or idiopathic pericarditis who were intolerant or refractory to conventional therapy, anakinra significantly improved symptom relief compared to conventional therapy alone, with 100% of patients reporting relief at discharge.

Patients receiving anakinra experienced a shorter time to symptom relief (approximately 3.75 days) and a lower recurrence rate during treatment (0% recurrence) compared to 40.9% recurrence in the conventional therapy group, highlighting its potential efficacy in managing pericarditis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of anakinra for idiopathic and non-idiopathic pericarditis refractory or intolerant to conventional therapy. Shaukat, MH., Singh, S., Davis, K., et al.[2022]

Anakinra significantly reduces C-reactive protein (CRP) levels in heart failure patients, suggesting it has anti-inflammatory effects, based on a meta-analysis of eight randomized controlled trials.

However, despite lowering CRP, anakinra did not improve exercise capacity or functional outcomes in heart failure patients, and treatment-related adverse events were minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anakinra in Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Mahfooz, K., Rana, A., Palagati, K., 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- ... The results demonstrate that anakinra significantly reduces the levels of CRP (C-reactive protein), with significant difference between anakinra ...

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

Results from the REcently Decompensated Heart failure ... The most robust finding of the current study is that anakinra reduces serum CRP levels in patients with decompensated HF. While this could be expected ...

3. academic.oup.com academic.oup.com/eurheartj/article/45/Supplement_1/ehae666.1077/7835353

Effects of anakinra on patients with heart failure below and ... We included 49 (67%) patients with age <60 years and 24 (33%) with age ≥60 years. The duration of treatment with anakinra was 4 [2-12] weeks.

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.031251

Differential Response to Interleukin‐1 Blockade With ... Of 32 patients, 15 (47%) had LVEF 50% to 59%, and 17 (53%) had LVEF ≥60%. The duration of anakinra treatment was 12 (2–12) weeks in both groups ...

5. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09581-w

Effectiveness of early Anakinra on cardiac function in children ... This systematic review finds that Anakinra may positively influence cardiac function, evidenced by significant improvements in LVEF and ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524170589

Comparison of Safety and Biological Efficacy of Anakinra ... Fewer cases of new-onset heart failure occurred in patients receiving anakinra in plastic or glass syringes compared with placebo. Anakinra stored in plastic ( ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01300650

NCT01300650 | Pilot Study of the Safety and Efficacy ... This is an open-label, non-randomized, pilot-study to evaluate the effect of Interleukin-1 blockade on exercise capacity in patients with heart failure.