Anakinra to Prevent Adverse Post-infarction Remodeling (2)

Heart Failure Clinical Trial

— VCU-ART2  

Official title:

Anakinra to Prevent Adverse Post-infarction Remodeling (2)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01175018
• Other study ID #: AHA 10SDG3030051
• Status: Completed
• Phase: Phase 2
• First received: July 30, 2010
• Last updated: July 6, 2013
• Start date: July 2010
• Est. completion date: December 2012

Study information

• Verified date: July 2013
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Acute myocardial infarction (AMI) remains a major cause of morbidity and mortality. Many patients die early during the course, and those who survive are at risk for dying late from adverse cardiac remodeling and heart failure.

The initial ischemic damage to the myocardium initiates an intense inflammatory response in promoting further cardiac dysfunction and heart failure. The investigators propose that an antiinflammatory strategy based on blockade of Interleukin-1 will quench the inflammatory response and lead to a more favorable cardiac remodeling process.

Description:

Acute myocardial infarction (AMI) remains a major cause of morbidity and mortality. Many patients die early during the course, and those who survive are at risk for dying late from adverse cardiac remodeling and heart failure.

The initial ischemic damage to the myocardium initiates an intense inflammatory response in promoting further cardiac dysfunction and heart failure. Interleukin-1 (IL-1) is the prototypical inflammatory cytokine involved in the tissue response to injury. In the experimental model of large anterior wall AMI in the mouse, IL-1 blockade using anakinra, a recombinant human IL-1 receptor antagonist ameliorates cardiac remodeling and improves survival following AMI. Although the mouse AMI model is helpful in understanding the events leading to adverse post-infarction cardiac remodeling and heart failure, the exact role of IL-1 in patients with AMI has not been completely characterized. The investigators propose to address this question by studying patients presenting with ST-segment elevation AMI (STEMI). Such patients are at high risk for in-hospital and long-term mortality and display several markers of inflammation. The investigators hypothesize that IL-1 blockade in patients STEMI with will limit the acute inflammatory response and prevent adverse cardiac remodeling, heart failure, and related morbidity.

The investigators hypothesize that treatment with anakinra will lead to more favorable cardiac remodeling. Left ventricular end-systolic volume index (LVESVi) is the preferred clinical marker of adverse cardiac remodeling and a strong predictor of heart failure-related mortality in patients with STEMI, and will be used as primary endpoint of the study. The investigators propose that anakinra will reduce the change in LVESVi from baseline to 10-14 weeks after STEMI, and will prevent, at least in part, other changes in cardiac function and exercise tolerance associated with adverse cardiac remodeling and heart failure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with STEMI will be asked to enroll according to the following inclusion criteria:

• age > 18 years,

• acute (<12 h) onset of chest pain associated with ST segment elevation (>2 mm) in 2 or more anatomically contiguous leads at ECG,

• and successful primary percutaneous coronary intervention.

Exclusion criteria:

• inability to give informed consent,

• late presentation (>12 h),

• unsuccessful revascularization procedure,

• hemodynamic instability including hypotension,

• prior Q-wave AMI,

• end-stage congestive heart failure (AHA/ACC class C-D, New York Heart Association IV), severe left ventricular dysfunction (EF<20%),

• severe valvular heart disease,

• pregnancy, dye allergy or contraindications to cardiac angiography and/or magnetic resonance imaging, coagulopathy (INR>1.5 or platelet count<50000/mm3),

• recent (<14 days) use of anti-inflammatory drugs (not including NSAIDs),

• chronic inflammatory disease (including but not limited to rheumatoid arthritis, systemic lupus erythematosus), and malignancy or any comorbidity limiting survival or conditions predicting inability to complete the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Heart Failure
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Anakinra
Anakinra 100 mg s.c. daily for 14 days
• Placebo
0.67 ml of NaCl 0.9% solution given subcutaneously daily for 14 days

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	American Heart Association

Country where clinical trial is conducted

United States, 

References & Publications (2)

Abbate A, Kontos MC, Grizzard JD, Biondi-Zoccai GG, Van Tassell BW, Robati R, Roach LM, Arena RA, Roberts CS, Varma A, Gelwix CC, Salloum FN, Hastillo A, Dinarello CA, Vetrovec GW; VCU-ART Investigators. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol. 2010 May 15;105(10):1371-1377.e1. doi: 10.1016/j.amjcard.2009.12.059. Epub 2010 Apr 2. — View Citation

Abbate A, Van Tassell BW, Biondi-Zoccai G, Kontos MC, Grizzard JD, Spillman DW, Oddi C, Roberts CS, Melchior RD, Mueller GH, Abouzaki NA, Rengel LR, Varma A, Gambill ML, Falcao RA, Voelkel NF, Dinarello CA, Vetrovec GW. Effects of interleukin-1 blockade w — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference between the anakinra arm and the placebo arm in change in left ventricular end-systolic volume indices from baseline to follow up exam at cardiac magnetic resonance imaging		10-14 weeks	Yes
Secondary	Difference between the anakinra arm and the placebo arm in change in left ventricular end-diastolic volume indices and ejection fraction values from baseline to follow up exam at cardiac magnetic resonance imaging		10-14 weeks	No
Secondary	Difference between the 2 arms in percentage of patients with: a) reverse remodeling [reduction in LVESVi or LVEDVi >5% or >10%]; b) adverse remodeling [increase >5% or >10%]; c) left ventricular ejection fraction change >5% or >10%		10-14 weeks	No
Secondary	Difference between the 2 arms in the peak VO2 or VE/VCo2 slope at 14 days, 10-14 weeks or the interval change in such measures		10-14 weeks	No
Secondary	Difference between the anakinra arm and the placebo arm in percentage of patients with a new diagnosis or admission to the hospital for heart failure		1 year	No
Secondary	Difference between the 2 arms in the number of adverse events including (a) all events; (b) events requiring unblinding; (c) events requiring termination; (d) death		1 year	Yes
Secondary	Difference between the 2 arm in the interval change in right ventricular dimensions and function	Right ventricular dimensions (RVEDVi and RVESVi measured at cardiac MR) and systolic function (RVEF measured at cardiac MR, TAPSE and tissue DOppler systolic velocity at echocardiogram)	12 weeks	No

External Links

•   VCU Pauley Heart Center