Anakinra to Prevent Adverse Post-infarction Remodeling (2) (VCU-ART2)

This study has been completed.
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01175018
First received: July 30, 2010
Last updated: May 9, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Acute Myocardial Infarction
Heart Failure
Drug: Anakinra
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Anakinra to Prevent Adverse Post-infarction Remodeling (2)

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Difference Between the Anakinra Arm and the Placebo Arm in Change in Left Ventricular End-systolic Volume Indices [ Time Frame: 10-14 weeks minus baseline ] [ Designated as safety issue: Yes ]
    Change in n left ventricular end-systolic volume indices from baseline to follow up exam at cardiac magnetic resonance imaging comparing anakinra- and placebo-treated patients.


Secondary Outcome Measures:
  • Difference Between the Anakinra Arm and the Placebo Arm in Change in Left Ventricular End-diastolic Volume Indices From Baseline to Follow up Exam at Cardiac Magnetic Resonance Imaging [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients in Each Group With Reverse Remodeling (Reduction in LVESVi >5%) [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Median Difference Between the 2 Arms in the Peak Oxygen Consumption (VO2) at 10-14 Weeks [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Incidence of Heart Failure [ Time Frame: 10-14 weeks ] [ Designated as safety issue: Yes ]
    Difference between the anakinra arm and the placebo arm in number of patients with a new diagnosis or admission to the hospital for heart failure

  • Number of Adverse Events in Each Group [ Time Frame: 10-14 weeks ] [ Designated as safety issue: Yes ]
  • Difference Between the 2 Arm in the Interval Change in Right Ventricular Ejection Fraction (RVEF) [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Difference Between the Anakinra Arm and the Placebo Arm in Change in Left Ventricular Ejection Fraction Values From Baseline to Follow up Exam at Cardiac Magnetic Resonance Imaging [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Median Difference Between the 2 Arms in the Ratio of Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope) at 10-14 Weeks [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients in Each Group With Reverse Remodeling (Reduction in LVESVi >10%) [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients in Each Group With Adverse Remodeling (LVESVi Increase >5%) Based Upon Cardiac Magnetic Resonance Imaging [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients in Each Group With Adverse Remodeling (LVESVi Increase >10%) [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients in Each Group With Left Ventricular Ejection Fraction Change >5% [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients in Each Group With Left Ventricular Ejection Fraction Change >10% [ Time Frame: 10-14 weeks ] [ Designated as safety issue: No ]
  • Number of Deaths in Each Group [ Time Frame: 10-14 weeks ] [ Designated as safety issue: Yes ]
  • Number of Adverse Events Requiring Withdrawal in Each Group [ Time Frame: 10-14 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: July 2010
Study Completion Date: December 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anakinra
Anakinra 100 mg injectable subcutaneously daily
Drug: Anakinra
Anakinra 100 mg s.c. daily for 14 days
Other Name: Kineret
Placebo Comparator: Placebo
0.67 ml of sodium chloride (NaCl) 0.9% solution
Drug: Placebo
0.67 ml of NaCl 0.9% solution given subcutaneously daily for 14 days
Other Name: NaCl 0.9%

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 110 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (American Heart Association [AHA]/American College of Cardiology [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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01175018

Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
American Heart Association
Investigators
Principal Investigator: Antonio Abbate, M.D., Ph.D. Virginia Commonwealth University
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01175018     History of Changes
Other Study ID Numbers: AHA 10SDG3030051 
Study First Received: July 30, 2010
Results First Received: October 22, 2013
Last Updated: May 9, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Virginia Commonwealth University:
Acute myocardial infarction
Heart Failure
Cardiac Remodeling

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

ClinicalTrials.gov processed this record on August 24, 2016