NCT00789724

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 2008

Shorter than P25 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2008

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

November 11, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 13, 2008

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2009

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

August 24, 2010

Completed
Last Updated

November 30, 2017

Status Verified

October 1, 2017

Enrollment Period

9 months

First QC Date

November 11, 2008

Results QC Date

July 30, 2010

Last Update Submit

October 24, 2017

Conditions

ST Segment Elevation Acute Myocardial Infarction

Keywords

acute myocardial infarction

Outcome Measures

Primary Outcomes (1)

  • Difference Between the Anakinra Arm and Placebo Arm in Change in End-systolic Volume Indices From Baseline to Follow up Exam 10-14 Weeks Later at Cardiac Magnetic Resonance Imaging.

    10-14 weeks

Other Outcomes (8)

  • Difference Between the 2 Arms in the Percentage of Patients With Any of the Following : a) End-systolic or End-diastolic Volume Index Increase >10%; b) Ejection Fraction Decrease >10%; c) E/E'>15 at Follow up

    10-14 weeks

  • Difference Between the 2 Arms in Change in the Number of Circulating Endothelial Progenitor Cells From Baseline to Follow up Exam

    10-14 weeks

  • Difference Between the 2 Arms in Change in Serum BNP Levels, C-reactive Protein, and Hemoglobin A1c% From Baseline to Follow up

    10-14 weeks

  • +5 more other outcomes

Study Arms (2)

Anakinra

EXPERIMENTAL

Anakinra 100 mg given daily by subcutaneous injection for 14 days

Drug: Anakinra

Placebo

PLACEBO COMPARATOR

0.67 ml of NaCl 0.9% solution

Drug: Placebo

Interventions

AnakinraDRUG

100 mg daily subcutaneous injection for 14 days

Also known as: Kineret (TM)
Anakinra
PlaceboDRUG

0.67 ml of NaCl 0.9% subcutaneously daily for 14 days

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (3)

  • 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.

    PMID: 39531530DERIVED

  • 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.

    PMID: 35170493DERIVED

  • 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.

    PMID: 25482680DERIVED

MeSH Terms

Interventions

Interleukin 1 Receptor Antagonist Protein

Intervention Hierarchy (Ancestors)

CytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Results Point of Contact

Title
Antonio Abbate, MD, PhD
Organization
VCU Pauley Heart Center
aabbate@mcvh-vcu.edu
8048280513

Study Officials

  • Antonio Abbate, MD

    Virginia Commonwealth University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 11, 2008

First Posted

November 13, 2008

Study Start

November 1, 2008

Primary Completion

August 1, 2009

Study Completion

August 1, 2009

Last Updated

November 30, 2017

Results First Posted

August 24, 2010

Record last verified: 2017-10

Locations

US(1)