Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2)

Background: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes.

Methods: TACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2's participants.

Results: At baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m², 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) µg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) µg/L and 0.30 (0.18, 0.51) µg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset.

Conclusions: TACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population.

Clinical trials registration: ClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185.