Trial to Assess Chelation Therapy in Critical Limb Ischemia

Launched by MT. SINAI MEDICAL CENTER, MIAMI · Jun 9, 2019

Keywords

ClinConnect Summary

The TACT3a trial is a research study that aims to test a new treatment using chelation therapy, which is designed to remove harmful metals from the body. This study specifically looks at how effective this therapy is in reducing serious health issues, such as heart problems or amputations, in patients with critical limb ischemia (CLI) related to diabetes. CLI is a condition where blood flow to the legs is severely restricted, often causing pain, ulcers, or even gangrene. The trial is currently recruiting participants who are at least 50 years old, have a history of diabetes, and have significant narrowing of the arteries in their legs.

To participate, individuals must meet certain criteria, including having severe pain or non-healing wounds in their legs due to CLI, and they should not be candidates for certain surgical procedures. If someone joins the trial, they will receive either the chelation therapy or a placebo (a non-active treatment) without knowing which one they are receiving. Participants will be closely monitored throughout the study to see how well the treatment works and if it helps improve their condition. This trial is an important step in finding new ways to help patients with critical limb ischemia and diabetes.

Gender

ALL

Eligibility 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:
• • \<7 days following lower extremity (infra-popliteal), carotid, or coronary revascularization.
• • 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 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
• • 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 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.