The trial to assess chelation therapy 2 (TACT2): Rationale and design

Gervasio A Lamas¹, Kevin J Anstrom², Ana Navas-Acien³, Robin Boineau⁴, Hwasoon Kim⁵, Yves Rosenberg⁶, Mario Stylianou⁶, Teresa L Z Jones⁷, Bonnie R Joubert⁸, Regina M Santella³, Esteban Escolar⁹, Y Wady Aude¹⁰, Vivian Fonseca¹¹, Thomas Elliott¹², Eldrin F Lewis¹³, Michael E Farkouh¹⁴, David M Nathan¹⁵, Ana C Mon⁹, Leigh Gosnell⁵, Jonathan D Newman¹⁶, Daniel B Mark⁵; TACT2 Investigators

Affiliations

¹ Division of Cardiology, Mount Sinai Medical Center, Miami Beach, FL, USA. Electronic address: gervasio.lamas@msmc.com.
² Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
³ Columbia University Mailman School of Public Health, New York, NY, USA.
⁴ National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD, USA.
⁵ Duke Clinical Research Institute, Duke University, Durham, NC, USA.
⁶ National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁷ National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
⁸ National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, USA.
⁹ Division of Cardiology, Mount Sinai Medical Center, Miami Beach, FL, USA.
¹⁰ Heart and Vascular Specialists of South Texas, McAllen, TX, USA.
¹¹ Tulane University School of Medicine, New Orleans, LA, USA.
¹² BC Diabetes, Vancouver, BC, USA.
¹³ Stanford University School of Medicine, Palo Alto, CA, USA.
¹⁴ Peter Munk Cardiac Centre, University of Toronto, ON, Canada.
¹⁵ Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶ New York University School of Medicine, New York, NY, USA.

PMID: 35598636
PMCID: PMC9434822
DOI: 10.1016/j.ahj.2022.05.013

Randomized Controlled Trial

The trial to assess chelation therapy 2 (TACT2): Rationale and design

Gervasio A Lamas et al. Am Heart J. 2022 Oct.

. 2022 Oct:252:1-11.

doi: 10.1016/j.ahj.2022.05.013. Epub 2022 May 19.

Authors

Affiliations

¹ Division of Cardiology, Mount Sinai Medical Center, Miami Beach, FL, USA. Electronic address: gervasio.lamas@msmc.com.
² Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
³ Columbia University Mailman School of Public Health, New York, NY, USA.
⁴ National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD, USA.
⁵ Duke Clinical Research Institute, Duke University, Durham, NC, USA.
⁶ National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁷ National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
⁸ National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, USA.
⁹ Division of Cardiology, Mount Sinai Medical Center, Miami Beach, FL, USA.
¹⁰ Heart and Vascular Specialists of South Texas, McAllen, TX, USA.
¹¹ Tulane University School of Medicine, New Orleans, LA, USA.
¹² BC Diabetes, Vancouver, BC, USA.
¹³ Stanford University School of Medicine, Palo Alto, CA, USA.
¹⁴ Peter Munk Cardiac Centre, University of Toronto, ON, Canada.
¹⁵ Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶ New York University School of Medicine, New York, NY, USA.

PMID: 35598636
PMCID: PMC9434822
DOI: 10.1016/j.ahj.2022.05.013

Abstract

Background: Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design.

Methods: TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or Na₂EDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI). TACT2 completed enrollment of 1000 subjects in December 2020, and infusions in December 2021. Subjects are followed for 2.5 to 5 years. The primary endpoint is time to first occurrence of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The trial has >;85% power to detect a 30% relative reduction in the primary endpoint. TACT2 also includes a Trace Metals and Biorepository Core Lab, to test whether benefits of treatment, if present, are due to chelation of lead and cadmium from patients. Design features of TACT2 were chosen to replicate selected features of the first TACT, which demonstrated a significant reduction in cardiovascular outcomes in the EDTA chelation arm compared with placebo among patients with a prior MI, with the largest effect in patients with diabetes.

Results: Results are expected in 2024.

Conclusion: TACT2 may provide definitive evidence of the benefit of edetate disodiumbased chelation on cardiovascular outcomes, as well as the clinical importance of longitudinal changes in toxic metal levels of participants.

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Conflict of interest statement

Declarations of interest: None.

Comment in

Chelation trial in patients with cardiovascular disease.
Yen TH, Yen JS. Yen TH, et al. Am Heart J. 2023 Feb;256:1. doi: 10.1016/j.ahj.2022.10.084. Epub 2022 Nov 3. Am Heart J. 2023. PMID: 36336079 No abstract available.

References

1. Lamas GA, Goertz C, Boineau R,Mark DB, Rozema T,Nahin RL, Drisko JA, and Lee KL (2012). Design of the Trial to Assess Chelation Therapy (TACT). Am. Heart J 163, 7–12. doi: 10.1016/j.ahj.2011.10.002. - DOI - PMC - PubMed
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The trial to assess chelation therapy 2 (TACT2): Rationale and design

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The trial to assess chelation therapy 2 (TACT2): Rationale and design

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