Trial to Assess Chelation Therapy 2 (TACT2)

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).

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Diabetes
• Intervention / Treatment: Drug: disodium EDTA; Dietary supplement: Oral Multi Vitamins/Minerals (OMVM); Drug: Placebo disodium EDTA; Dietary supplement: Placebo Oral Multi Vitamins/Minerals (OMVM)

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.

• Study Type: Interventional
• Enrollment (Actual): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami Beach, Florida, United States, 33132
      • Mount Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

   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. Site personnel are to call the CCC to discuss heparin allergy.
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. 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.

10. Prior participation in TACT.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active/Active; Active disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)	Drug: disodium EDTA; Other Names: EDTA; Dietary supplement: Oral Multi Vitamins/Minerals (OMVM)
Active Comparator: Active/Placebo; Active disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)	Drug: disodium EDTA; Other Names: EDTA
Active Comparator: Placebo/ Active; Placebo disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)	Dietary supplement: Oral Multi Vitamins/Minerals (OMVM); Drug: Placebo disodium EDTA
Placebo Comparator: Placebo/Placebo; Placebo disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)	Drug: Placebo disodium EDTA; Dietary supplement: Placebo Oral Multi Vitamins/Minerals (OMVM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
A composite of all-cause mortality, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina	5 years

Collaborators and Investigators

• Sponsor: Mt. Sinai Medical Center, Miami
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Center for Complementary and Integrative Health (NCCIH); Duke Clinical Research Institute
• Investigators: Study Chair: Gervasio A Lamas, MD, Mount Sinai Medical Center of Florida; Principal Investigator: Kevin J Anstrom, PhD, University of North Carolina, Chapel Hill; Principal Investigator: Daniel B Mark, MD, Duke University (Duke Clinical Research Institute)

Publications and helpful links

General Publications

• Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL, Drisko JA, Lee KL. Design of the Trial to Assess Chelation Therapy (TACT). Am Heart J. 2012 Jan;163(1):7-12. doi: 10.1016/j.ahj.2011.10.002.
• Escolar E, Lamas GA, Mark DB, Boineau R, Goertz C, Rosenberg Y, Nahin RL, Ouyang P, Rozema T, Magaziner A, Nahas R, Lewis EF, Lindblad L, Lee KL. The effect of an EDTA-based chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the Trial to Assess Chelation Therapy (TACT). Circ Cardiovasc Qual Outcomes. 2014 Jan;7(1):15-24. doi: 10.1161/CIRCOUTCOMES.113.000663. Epub 2013 Nov 19.
• Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL, Lindblad L, Lewis EF, Drisko J, Lee KL; TACT Investigators. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA. 2013 Mar 27;309(12):1241-50. doi: 10.1001/jama.2013.2107.
• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, Rozema T, Nahin RL, Terry Chappell L, Lindblad L, Lewis EF, Drisko J, Lee KL. EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy. Am Heart J. 2014 Jul;168(1):37-44.e5. doi: 10.1016/j.ahj.2014.02.012. Epub 2014 Apr 2.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: April 5, 2016
• First Submitted That Met QC Criteria: April 5, 2016
• First Posted (Estimated): April 11, 2016

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: chelation
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Anticoagulants; Antidotes; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Calcium Chelating Agents; Vitamins; Edetic Acid; Pentetic Acid
• Other Study ID Numbers: AT009149-01; UH3AT009149 (U.S. NIH Grant/Contract); UH3AT009150 (U.S. NIH Grant/Contract); R01AT009273 (U.S. NIH Grant/Contract); U24AT009150 (U.S. NIH Grant/Contract)