Trial to Assess Chelation Therapy in Critical Limb Ischemia

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mt. Sinai Medical Center, Miami
• Treatments: Edetic Acid; Pentetic Acid

Criteria

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) <40 mmHg.

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

• Not a candidate or a failed candidate for surgical or transcatheter revascularization;

• Able to give informed consent.

Exclusion Criteria:

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

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

• Subjects with extensive gangrene extending above the Metatarsophalangeal (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; if only 1 infusion took place, patient cannot be enrolled for at least 12 months after said infusion.

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

• Allergy to any components of the study drug

• Coronary or carotid revascularization within 3 months

• 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

• Estimated glomerular filtration ratee (GFR) < 30 mL/min per 1.73 m2 or lower (CKD stages 1-3) calculated with the Modification of Diet in Renal Disease Study (MDRD) equation

• Known or suspected acute kidney injury using prevalent Kidney Disease: Improving Global Outcomes (KDIGO) criteria

• 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 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.