Trial to Assess Chelation Therapy 2

NCT02733185 | Completed Phase 3 Results DMC FDA Drug

• 5 other identifiers: AT009149-01UH3AT009149UH3AT009150R01AT009273U24AT009150
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

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).

Conditions

Diabetes; Myocardial Infarction

Keywords

chelation

Outcome Measures

Primary Outcomes (1)

• Primary Composite Outcome

  Time to first event: myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or death from any cause

  48 month follow-up (median)

Secondary Outcomes (2)

• Secondary Composite Outcome

  48 month follow-up (median)

• Secondary Outcome

  All-Cause Mortality was assessed through study completion, up to 48 months (median)

Study Arms (4)

Active/Active

ACTIVE COMPARATOR

Active disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)

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

Active/Placebo

ACTIVE COMPARATOR

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

Drug: disodium EDTA

Placebo/ Active

ACTIVE COMPARATOR

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

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

Placebo/Placebo

PLACEBO COMPARATOR

Placebo disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)

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

Interventions

disodium EDTA DRUG

IV Disodium Ethylene diamine tetra acetic acid in 500 cc

Also known as: EDTA

Active/Active; Active/Placebo

Oral Multi Vitamins/Minerals (OMVM) DIETARY_SUPPLEMENT

6 tablets of Multi-vitamin/Multimineral daily

Active/Active; Placebo/ Active

Placebo disodium EDTA DRUG

IV Placebo comparator- 500 normal saline

Placebo/ Active; Placebo/Placebo

Placebo Oral Multi Vitamins/Minerals (OMVM) DIETARY_SUPPLEMENT

6 tablets of a placebo Multi-vitamin/Multimineral daily

Placebo/Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mt. Sinai Medical Center, Miami: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Duke Clinical Research Institute: collaborator

Study Sites (1)

Mount Sinai Medical Center

Miami Beach, Florida, 33132, United States

Location

Related Publications (8)

• 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.

  PMID: 23532240 BACKGROUND

• 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.

  PMID: 24254885 BACKGROUND

• 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.

  PMID: 24952858 BACKGROUND

• 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.

  PMID: 22172430 BACKGROUND

• Lamas GA, Anstrom KJ, Navas-Acien A, Boineau R, Kim H, Rosenberg Y, Stylianou M, Jones TLZ, Joubert BR, Santella RM, Escolar E, Aude YW, Fonseca V, Elliott T, Lewis EF, Farkouh ME, Nathan DM, Mon AC, Gosnell L, Newman JD, Mark DB; TACT2 Investigators. The trial to assess chelation therapy 2 (TACT2): Rationale and design. Am Heart J. 2022 Oct;252:1-11. doi: 10.1016/j.ahj.2022.05.013. Epub 2022 May 19.

  PMID: 35598636 BACKGROUND

• Navas-Acien A, Santella RM, Joubert BR, Huang Z, Lokhnygina Y, Ujueta F, Gurvich I, LoIacono NJ, Ravalli F, Ward CD, Jarrett JM, Salazar AL, Boineau R, Jones TLZ, Mark DB, Newman JD, Nathan DM, Anstrom KJ, Lamas GA. Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2). Am Heart J. 2024 Jul;273:72-82. doi: 10.1016/j.ahj.2024.04.005. Epub 2024 Apr 15.

  PMID: 38621575 BACKGROUND

• Ujueta F, Lamas GA, Anstrom KJ, Navas-Acien A, Boineau R, Rosenberg Y, Stylianou M, Jones TLZ, Joubert BR, Yu Q, Wen J, Nemeth H, Huang Z, Fonseca V, Nathan DM, Uwaifo G, Arenas IA, Luo L, Baker J, Visentin D, Paixao A, Schmedtje JF Jr, Mark DB; TACT2 Investigators. Multivitamins After Myocardial Infarction in Patients With Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2025 May 1;185(5):540-548. doi: 10.1001/jamainternmed.2024.8408.

  PMID: 40029647 DERIVED

• Lamas GA, Anstrom KJ, Navas-Acien A, Boineau R, Nemeth H, Huang Z, Wen J, Rosenberg Y, Stylianou M, Jones TLZ, Joubert BR, Yu Q, Santella RM, Mon AC, Ujueta F, Escolar E, Nathan DM, Fonseca VA, Aude YW, Ehrman JK, Elliott T, Prashad R, Lewis EF, Lopes RD, Farkouh ME, Elliott AM, Newman JD, Mark DB; TACT2 Investigators. Edetate Disodium-Based Chelation for Patients With a Previous Myocardial Infarction and Diabetes: TACT2 Randomized Clinical Trial. JAMA. 2024 Sep 10;332(10):794-803. doi: 10.1001/jama.2024.11463.

  PMID: 39141382 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Myocardial Infarction

Interventions

Edetic Acid; Minerals

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Inorganic Chemicals

Limitations and Caveats

Primary analyses were restricted to a modified intention-to-treat. Treatment adherence was imperfect. 12% of participants were lost to follow-up or withdrew consent.

Results Point of Contact

• Title: Dr. Gervasio Lamas
• Organization: Mount Sinai Medical Center of Florida

Gervasio.Lamas@msmc.com

305-674-2162

Study Officials

• Gervasio A Lamas, MD

  Mount Sinai Medical Center of Florida

  STUDY CHAIR

• Kevin J Anstrom, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Daniel B Mark, MD

  Duke University (Duke Clinical Research Institute)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: TACT2 Study Chair

Study Record Dates

• First Submitted: April 5, 2016
• First Posted: April 11, 2016
• Study Start: October 1, 2016
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: March 30, 2025
• Results First Posted: October 1, 2024

Record last verified: 2025-03

Locations

US (1)