Anakinra to Prevent Post-infarction Remodeling

NCT ID: NCT00789724

Last Updated: 2017-11-30

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2009-08-31

Brief Summary

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Thousands of patients die daily from early and late complications of a heart attack (acute myocardial infarction, AMI). Patients surviving AMI remain at high risk of death from adverse cardiac remodeling (dysfunction and enlargement of the heart) leading to heart failure (weakening of the heart).

Current interventions proven to reduce adverse remodeling and progression to heart failure include early reperfusion (restoring blood flow to the heart muscle) and long-term use of medicines that block the effects of hormones (such as angiotensin II, norepinephrine and aldosterone) involved in adverse remodeling. Despite these treatments, however, many patients continue to develop heart failure within 1 year of AMI. These patients are at very high risk of death.

Numerous changes occur in the hearts of patients after AMI that lead to adverse remodeling. Ischemia (lack of oxygen) and infarction (cell damage) lead to increased interleukin-1 (IL-1) production in the heart. IL-1 plays a critical role in adverse cardiac remodeling by coordinating the inflammatory pathway (leading to wound healing) and apoptotic pathway (leading to cell death).

In opposition to IL-1 activity, the human body produces a natural IL-1 receptor antagonist that blocks the effects of IL-1. The drug form of this IL-1 receptor antagonist (anakinra) is currently FDA approved for the treatment of rheumatoid arthritis, an inflammatory disease characterized by excessive IL-1 activity. Experimental studies show that anakinra is able to prevent cardiac remodeling and improve survival in mice after AMI.

We hypothesize that anakinra will show similar benefits in human patients by preventing adverse remodeling and heart failure after AMI.

Detailed Description

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Conditions

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ST Segment Elevation Acute Myocardial Infarction

Keywords

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acute myocardial infarction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Anakinra

Anakinra 100 mg given daily by subcutaneous injection for 14 days

Group Type EXPERIMENTAL

Anakinra

Intervention Type DRUG

100 mg daily subcutaneous injection for 14 days

Placebo

0.67 ml of NaCl 0.9% solution

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

0.67 ml of NaCl 0.9% subcutaneously daily for 14 days

Interventions

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Anakinra

100 mg daily subcutaneous injection for 14 days

Intervention Type DRUG

Placebo

0.67 ml of NaCl 0.9% subcutaneously daily for 14 days

Intervention Type DRUG

Other Intervention Names

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Kineret (TM)

Eligibility Criteria

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Inclusion Criteria

* Age \>18 years
* Acute (\<24 hours) onset of chest pain
* New or presumably new ST elevation on ECG
* Planned coronary angiography for percutaneous revascularization

Exclusion Criteria

* Inability to give informed consent
* Late presentation (\>24 hours)
* Unsuccessful revascularization or urgent coronary bypass surgery
* Hemodynamic instability
* End-stage congestive heart failure (AHA/ACC stage C/D, NYHA class IV)
* Preexisting severe LV dysfunction (LVEF\<20%) or severe valvular disease
* Severe asthma
* Pregnancy ( pre-enrollment pregnancy test)
* Contraindications to cardiac MRI or cardiac angiography
* Severe coagulopathy (INR\>2.0, Platelet count\<50,000/mm3)
* Severe renal insufficiency (creatinine clearance \<30 ml/min/m2)
* Recent (\<14 days) use of anti-inflammatory drugs (NSAIDS excluded)
* Chronic inflammatory disease
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Virginia Commonwealth University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Antonio Abbate, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

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Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Denicolai M, Morello M, Golino M, Corna G, Del Buono MG, Agatiello CR, Van Tassell BW, Abbate A. Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity. J Cardiovasc Pharmacol. 2025 Mar 1;85(3):200-210. doi: 10.1097/FJC.0000000000001652.

Reference Type DERIVED
PMID: 39531530 (View on PubMed)

Del Buono MG, Damonte JI, Chiabrando JG, Markley R, Turlington J, Trankle CR, Kang L, Biondi-Zoccai G, Van Tassell BW, Abbate A. Effect of IL-1 Blockade With Anakinra on Heart Failure Outcomes in Patients With Anterior Versus Nonanterior ST Elevation Myocardial Infarction. J Cardiovasc Pharmacol. 2022 Jun 1;79(6):774-780. doi: 10.1097/FJC.0000000000001240.

Reference Type DERIVED
PMID: 35170493 (View on PubMed)

Abbate A, Kontos MC, Abouzaki NA, Melchior RD, Thomas C, Van Tassell BW, Oddi C, Carbone S, Trankle CR, Roberts CS, Mueller GH, Gambill ML, Christopher S, Markley R, Vetrovec GW, Dinarello CA, Biondi-Zoccai G. 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). Am J Cardiol. 2015 Feb 1;115(3):288-92. doi: 10.1016/j.amjcard.2014.11.003. Epub 2014 Nov 13.

Reference Type DERIVED
PMID: 25482680 (View on PubMed)

Other Identifiers

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VCU-ART

Identifier Type: -

Identifier Source: org_study_id