ST Segment Elevation Acute Myocardial Infarction Clinical Trial
— VCU-ARTOfficial title:
Recombinant Human Interleukin-1 Receptor Antagonist, Anakinra, to Prevent Post-infarction Remodeling: the Virginia Commonwealth University Anakinra Remodeling Trial (VCU-ART)
| Verified date | October 2017 |
| Source | Virginia Commonwealth University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 10 |
| Est. completion date | August 2009 |
| Est. primary completion date | August 2009 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Virginia Commonwealth University | Richmond | Virginia |
| Lead Sponsor | Collaborator |
|---|---|
| Virginia Commonwealth University |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | 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 | ||
| Other | Difference Between the 2 Arms in Change in the Number of Circulating Endothelial Progenitor Cells From Baseline to Follow up Exam | 10-14 weeks | ||
| Other | 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 | ||
| Other | Difference Between the 2 Arms in the Incidence of Significant Cardiac Arrhythmias in the Acute Phase | 48 hours | ||
| Other | 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 | 10-14 weeks | ||
| Other | Difference Between the 2 Arms in Change in Oxygen Uptake Kinetics From Baseline to Follow up Exam at Submaximal Cardiopulmonary Exercise Test | 10-14 weeks | ||
| Other | 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 | 10-14 weeks | ||
| Other | 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 | 10-14 weeks | ||
| Primary | 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 |