Trial to Assess Chelation Therapy in Critical Limb Ischemia

TACT3a is a double blind, placebo-controlled, randomized trial to test a novel therapy, edetate disodium-based chelation of environmentally acquired toxic metals, to reduce cardiovascular events including amputation in high-risk diabetic patients.

Inclusion Criteria: * 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. * Significant stenosis (≥ 75%) of two or more infra-popliteal arteries in the affected limb as verified by at least one imaging technique (angiography, magnetic resonance angiogram, coronary computed tomography angiogram, or doppler examination) within 6 months prior to enrollment; * History of CLI defined as moderate or high-risk infra-popliteal chronic critical limb ischemia (Rutherford Clinical Severity Score 4 or 5) defined as: * The presence of rest pain or non-healing ulceration or gangrene for at least 2 weeks plus documentation of severely compromised tissue perfusion: * If there is tissue loss, a resting ankle systolic pressure of ≤ 60 mmHg in the affected limb; or a resting toe systolic pressure of ≤ 40 mmHg or a tissue perfusion pressure (TPP) \160/100 * No venous access * eGFR \< 30 mL/min per 1.73 m2 or lower (CKD stages 1-3) calculated with MDRD * Known or suspected acute kidney injury using prevalent KDIGO criteria45 * Platelet count \ 2.0 times the upper limit of normal (this will require clearance by the Study PI) * Diseases of copper, iron, or calcium metabolism (other than osteopenia or osteoporosis, or simple iron deficiency). These require evaluation by the Study PI * Inability to tolerate the study-required fluid load * Other medical condition likely to affect patient survival within 3 years * Women of child-bearing potential * Any factor that suggests that the potential participant will not be able to adhere to the protocol.