Trial to Assess Chelation Therapy 2 (TACT2)

• ClinicalTrials.gov Identifier: NCT02733185
• Recruitment Status: Active, not recruiting
• First Posted: April 11, 2016
• Last Update Posted: March 15, 2023
• Sponsor: Mt. Sinai Medical Center, Miami
• Collaborators: National Center for Complementary and Integrative Health (NCCIH); National Heart, Lung, and Blood Institute (NHLBI); Duke Clinical Research Institute
• Information provided by (Responsible Party): Gervasio Lamas, MD, Mt. Sinai Medical Center, Miami

Tracking Information

• First Submitted Date: April 5, 2016
• First Posted Date: April 11, 2016
• Last Update Posted Date: March 15, 2023
• Actual Study Start Date: October 2016
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 5, 2016): A composite of all-cause mortality, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina [ Time Frame: 5 years ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial to Assess Chelation Therapy 2
• Official Title: Trial to Assess Chelation Therapy 2
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention

Condition

• Diabetes
• Myocardial Infarction

Intervention

• Drug: disodium EDTA
  Other Name: EDTA
• Dietary Supplement: Oral Multi Vitamins/Minerals (OMVM)
• Drug: Placebo disodium EDTA
• Dietary Supplement: Placebo Oral Multi Vitamins/Minerals (OMVM)

Study Arms

• Active Comparator: Active/Active
  Active disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)
  Interventions:

  • Drug: disodium EDTA
  • Dietary Supplement: Oral Multi Vitamins/Minerals (OMVM)
• Active Comparator: Active/Placebo
  Active disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)
  Intervention: Drug: disodium EDTA
• Active Comparator: Placebo/ Active
  Placebo disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)
  Interventions:

  • 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)
  Interventions:

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

Publications *

• 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.
• 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, 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 8, 2021): 1000
• Original Estimated Enrollment (submitted: April 5, 2016): 1200
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02733185
• 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 )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Gervasio Lamas, MD, Mt. Sinai Medical Center, Miami
• Original Responsible Party: Same as current
• Current Study Sponsor: Mt. Sinai Medical Center, Miami
• Original Study Sponsor: Same as current

Collaborators

• National Center for Complementary and Integrative Health (NCCIH)
• National Heart, Lung, and Blood Institute (NHLBI)
• 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)

• PRS Account: Mt. Sinai Medical Center, Miami
• Verification Date: March 2023