Trial to Assess Chelation Therapy 2

The primary objective of TACT2, therefore, is to determine if the chelation-based strategy increases the time to the first occurrence of any of the components of the TACT2 primary endpoint: all-cause mortality, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina compared to the placebo chelation strategy.

TACT2 is a 2x2 factorial trial testing 40-weekly edetate disodium-based chelation infusions and twice daily high-dose oral multivitamins and multiminerals (OMVM) in a placebo-controlled design.

TACT2 is being carried out to replicate the findings of TACT1, which found a striking reduction of recurrent cardiovascular events in post-MI diabetic patients receiving edetate disodium-based chelation therapy.

Inclusion criteria

• Age: ≥ 50 years
• History of diabetes, defined as medical record evidence or patient report of currently using insulin or oral hypoglycemic agents, or with a history of fasting blood glucose measurement of 126 mg/dL or higher, or a history of HbA1c of 6.5% or higher.
• History of myocardial infarction based on the Universal Definition of MI.

• When information about the MI hospitalization is available, all MI types except Type 2 qualify for study entry.
• When information about the MI hospitalization is not available, a wall motion abnormality on imaging or a perfusion defect on scan that corresponds to a coronary distribution, whether or not accompanied by pathological Q waves in the appropriate distribution, will qualify the patient for study entry. This criterion requires a call to the CCC for case review.

Exclusion criteria

• Baseline serum creatinine >2.0 mg/dL.
• HbA1C >11%.
• Myocardial infarction within 6 weeks of randomization.
• History of allergic reactions to EDTA or any other components of the chelation solution, including heparin. Site personnel are to call the CCC to discuss heparin allergy.
• Coronary or peripheral arterial revascularization procedure performed within the last 6 months.
• Planned revascularization procedure in the 6 months following enrollment.
• Heart failure hospitalization within 6 months prior to enrollment or in clinical heart failure at the time of proposed enrollment (such as NYHA Class 3 dyspnea + rales >basilar, and additional signs of fluid overload). Such patients may be treated with diuretics and enrolled when stable.
• Poor or no venous access in the upper extremities.
• a. Prior intravenous chelation therapy consisting of > 1 infusion within 5 years; if only 1 infusion took place, patient cannot be enrolled for at least 12 months after said infusion.

b. Oral chelation therapy with an approved oral chelating agent within 2 years.

• Prior participation in TACT.
• Baseline platelet count <100,000.
• History of cigarette smoking within the last 3 months.
• ALT or AST > 2.0 times the upper limit of normal.
• Wilson's disease, hemochromatosis, or parathyroid disease.
• Any medical condition including a current diagnosis of cancer (except non-melanoma skin cancer) that will limit patient survival over the duration of the trial.
• Any factor that suggests that the potential participant will not be able to adhere to the protocol.
• Women of child-bearing potential including those with plans for post-menopausal in vitro fertilization or other reproductive technology.