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:

1. Age: ≥ 50 years

2. 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.

3. History of myocardial infarction based on the Universal Definition of MI. 36

1. When information about the MI hospitalization is available, all MI types except
Type 2 qualify for study entry.

2. 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:

1. Baseline serum creatinine >2.0 mg/dL.

2. HbA1C >11%.

3. Myocardial infarction within 6 weeks of randomization.

4. History of allergic reactions to EDTA or any other components of the chelation
solution, including heparin.

5. Coronary or peripheral arterial revascularization procedure performed within the last
6 months.

6. Planned revascularization procedure in the 6 months following enrollment.

7. 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.

8. Poor or no venous access in the upper extremities.

9. Prior intravenous chelation therapy within 5 years or oral chelation within 2 years of
the time of proposed randomization.

10. Prior participation in TACT1.

11. Baseline platelet count <100,000.

12. History of cigarette smoking within the last 3 months.

13. ALT or AST > 2.0 times the upper limit of normal.

14. Wilson's disease, hemochromatosis, or parathyroid disease.

15. 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.

16. Any factor that suggests that the potential participant will not be able to adhere to
the protocol.

17. Women of child-bearing potential including those with plans for post-menopausal in
vitro fertilization or other reproductive technology.