Clinical trial NCT02733185: Trial to Assess Chelation Therapy 2
Official title: Trial to Assess Chelation Therapy 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Myocardial Infarction
Keywords: chelation
Lead sponsor: Mt. Sinai Medical Center, Miami
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Duke Clinical Research Institute
First posted: 2016-04-11
Enrollment: 1000
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Primary Composite Outcome
timeFrame: 48 month follow-up (median)
Secondary outcomes:
measure: Secondary Composite Outcome
timeFrame: 48 month follow-up (median)
measure: Secondary Outcome
timeFrame: All-Cause Mortality was assessed through study completion, up to 48 months (median)
Other outcomes:
Locations:
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
Study officials:
affiliation: Mount Sinai Medical Center of Florida
name: Gervasio A Lamas, MD
role: STUDY_CHAIR
affiliation: University of North Carolina, Chapel Hill
name: Kevin J Anstrom, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University (Duke Clinical Research Institute)
name: Daniel B Mark, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.