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

Trial Summary

What is the purpose of this trial?

End-stage heart failure (HF) is a progressive illness with a mortality rate similar to most advanced cancers.Roughly 5% of patients with HF have end-stage disease that is refractory to medical therapy (stage D heart failure). When patients reach this point in their disease, the only treatments known to prolong life are cardiac transplantation or left ventricular assist devices. In patients who do not qualify for these options, or elect a palliative approach, inotropes are frequently used to improve hemodynamics through an increase in cardiac output and reduction in filling pressures. While inotropes provide profound symptomatic relief, these benefits are accompanied by significant risks of progressive adverse cardiac remodeling, arrhythmias, and sudden death. There is, therefore, an urgent need to develop strategies to reduce the dose or duration of inotrope use in the management of patients with stage D of HF.

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.

What data supports the effectiveness of the drug Anakinra for heart failure?

Anakinra has been shown to reduce inflammation in heart failure patients by lowering levels of C-reactive protein (CRP), a marker of inflammation. However, it did not improve exercise capacity or heart function in these patients. ^{1 2 3 4 5}

How is the drug Anakinra unique for treating heart failure?

Anakinra is unique for treating heart failure because it targets inflammation by blocking interleukin-1, a protein involved in the inflammatory response, which is not a common approach in standard heart failure treatments. It is administered through daily subcutaneous injections, which is different from many heart failure medications that are typically taken orally. ^{1 4 6 7 8}

Research Team

Azita Talasaz

Principal Investigator

Virginia Coomonwealth University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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 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, 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations. [2022]

2. Iran 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. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Anakinra in Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2023]

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

Interleukin-1 Blockade in Acute Decompensated Heart Failure: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study. [2018]

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

Effectiveness and Safety of Anakinra for Management of Refractory Pericarditis. [2015]

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

Anakinra in Recurrent Pericarditis: Current Evidence on Clinical Use, Effectiveness, and Safety. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy of anakinra for idiopathic and non-idiopathic pericarditis refractory or intolerant to conventional therapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Off-Label studies on anakinra in dermatology: a review. [2022]