Trial to Assess Chelation Therapy 2

Phase 3

Completed

Conditions: Myocardial Infarction
Diabetes

Interventions: Drug: disodium EDTA
Dietary Supplement: Oral Multi Vitamins/Minerals (OMVM)
Drug: Placebo disodium EDTA
Dietary Supplement: Placebo Oral Multi Vitamins/Minerals (OMVM)

Registration Number: NCT02733185

Lead Sponsor: Mt. Sinai Medical Center, Miami

Brief Summary: Trial to Assess Chelation Therapy 2 (TACT2) is a randomized, double blind controlled factorial clinical trial of edetate disodium-based chelation and high-dose oral vitamins and minerals to prevent recurrent cardiac events in diabetic patients with a prior myocardial infarction (MI).

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1000

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.
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

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Active/Active	disodium EDTA	Active disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)
Active/Active	Oral Multi Vitamins/Minerals (OMVM)	Active disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)
Active/Placebo	disodium EDTA	Active disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)
Placebo/ Active	Oral Multi Vitamins/Minerals (OMVM)	Placebo disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)
Placebo/ Active	Placebo disodium EDTA	Placebo disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)
Placebo/Placebo	Placebo disodium EDTA	Placebo disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)
Placebo/Placebo	Placebo Oral Multi Vitamins/Minerals (OMVM)	Placebo disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)

Primary Outcome Measures

Name	Time	Method
Primary Composite Outcome	48 month follow-up (median)	Time to first event: myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or death from any cause

Secondary Outcome Measures

Name	Time	Method
Secondary Composite Outcome	48 month follow-up (median)	Time to first event: myocardial infarction, stroke, or death from cardiovascular causes
Secondary Outcome	All-Cause Mortality was assessed through study completion, up to 48 months (median)	Time to All-Cause mortality