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Anakinra to Prevent Post-infarction Remodeling (VCU-ART)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00789724
First received: November 11, 2008
Last updated: February 21, 2012
Last verified: September 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
ST Segment Elevation Acute Myocardial Infarction
 Drug: Anakinra
Drug: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Recombinant Human Interleukin-1 Receptor Antagonist, Anakinra, to Prevent Post-infarction Remodeling: the Virginia Commonwealth University Anakinra Remodeling Trial (VCU-ART)

Resource links provided by NLM:

Drug Information available for: Anakinra
U.S. FDA Resources

Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • 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. [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Difference Between the 2 Arms in Change in End-diastolic Volume Indices and Ejection Fraction Values From Baseline to Follow up Exam at Cardiac Magnetic Resonance Imaging [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Difference Between the 2 Arms in Change in E/E' Ratios and Myocardial Performance (Tei) Indices From Baseline to Follow up Exam at Transthoracic Echo-color-Doppler Cardiac Exam [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Difference Between the 2 Arms in Change in Oxygen Uptake Kinetics From Baseline to Follow up Exam at Submaximal Cardiopulmonary Exercise Test [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Difference Between the 2 Arms in Change in the Number of Circulating Endothelial Progenitor Cells From Baseline to Follow up Exam [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Difference Between the 2 Arms in Change in Serum BNP Levels, C-reactive Protein, and Hemoglobin A1c% From Baseline to Follow up [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Difference Between the 2 Arms in the Incidence of Significant Cardiac Arrhythmias in the Acute Phase [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
  • Difference Between the 2 Arms in the Number of Adverse Effects Including a) All Events; b) All Events Requiring Unblinding of the Treatment; c) All Events Requiring Early Termination of the Intervention [ Time Frame: 10-14 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 10
Study Start Date: November 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anakinra
Anakinra 100 mg given daily by subcutaneous injection for 14 days
 Drug: Anakinra
100 mg daily subcutaneous injection for 14 days
Other Name: Kineret (TM)
Placebo Comparator: Placebo
0.67 ml of NaCl 0.9% solution
 Drug: Placebo
0.67 ml of NaCl 0.9% subcutaneously daily for 14 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00789724

Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Principal Investigator: Antonio Abbate, MD Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00789724     History of Changes
Other Study ID Numbers: VCU-ART
Study First Received: November 11, 2008
Results First Received: July 30, 2010
Last Updated: February 21, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
acute myocardial infarction

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
 Cardiovascular Diseases
Vascular Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013