Anakinra to Prevent Post-infarction Remodeling (VCU-ART)
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.
|ST Segment Elevation Acute Myocardial Infarction||Drug: Anakinra Drug: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, 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)|
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Difference Between the 2 Arms in the Incidence of Significant Cardiac Arrhythmias in the Acute Phase [ Time Frame: 48 hours ]
- 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 ]
|Study Start Date:||November 2008|
|Study Completion Date:||August 2009|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
Anakinra 100 mg given daily by subcutaneous injection for 14 days
100 mg daily subcutaneous injection for 14 days
Other Name: Kineret (TM)
Placebo Comparator: Placebo
0.67 ml of NaCl 0.9% solution
0.67 ml of NaCl 0.9% subcutaneously daily for 14 days
Please refer to this study by its ClinicalTrials.gov identifier: NCT00789724
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Antonio Abbate, MD||Virginia Commonwealth University|