Trial to Assess Chelation Therapy in Critical Limb Ischemia

Inclusion Criteria:

• Age ≥ 50 years

• History of diabetes, defined as medical record evidence or patient report ofcurrently using insulin or oral hypoglycemic agents, or with a history of fastingblood glucose measurement of 126 mg/dL or higher, or a history of HbA1c of 6.5% orhigher.

• Significant stenosis (≥ 75%) of two or more infra-popliteal arteries in the affectedlimb as verified by at least one imaging technique (angiography, magnetic resonanceangiogram, coronary computed tomography angiogram, or doppler examination) within 6months prior to enrollment;

• History of CLI defined as moderate or high-risk infra-popliteal chronic criticallimb ischemia (Rutherford Clinical Severity Score 4 or 5) defined as:

• The presence of rest pain or non-healing ulceration or gangrene for at least 2weeks plus documentation of severely compromised tissue perfusion:

• If there is tissue loss, a resting ankle systolic pressure of ≤ 60 mmHg in theaffected limb; or a resting toe systolic pressure of ≤ 40 mmHg or a tissueperfusion pressure (TPP) <40 mmHg.

• If there is no tissue loss, a resting ankle pressure of ≤ 50 mmHg or restingtoe systolic pressure of ≤ 30 mmHg or a tissue perfusion pressure (TPP) < 30mmHg.

• Not a candidate or a failed candidate for surgical or transcatheterrevascularization;

• Able to give informed consent.

Exclusion Criteria:

• <7 days following lower extremity (infra-popliteal), carotid, or coronaryrevascularization.

• Arterial insufficiency in the lower extremity as the result of a non-atheroscleroticdisorder.

• Subjects with evidence of active infection (e.g., cellulitis, osteomyelitis) or deepulceration exposing bone or tendon or extensive heel ulceration

• Subjects with extensive gangrene extending above the MT joint

• Subjects in whom there is severe pain at rest uncontrollable with pain medications

• Prior intravenous chelation therapy consisting of > 1 infusion within 5 years; ifonly 1 infusion took place, patient cannot be enrolled for at least 12 months aftersaid infusion.

• Oral chelation with an FDA-approved chelating agent within 2 years

• Allergy to any components of the study drug

• Planned leg revascularization within 1 month of enrollment

• Symptomatic or clinically evident acute heart failure

• Heart failure hospitalization within 3 months

• Blood pressure >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 <100,000/mm3

• Cigarette smoking within the last 3 months

• Liver disease or Alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 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 orosteoporosis, 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 adhereto the protocol.