Assessing chelation therapy for critical limb ischemia in diabetic patients

Trial to Assess Chelation Therapy in Critical Limb Ischemia

This study is testing if a special treatment called chelation therapy can help diabetic patients with critical limb ischemia avoid serious heart problems and amputations.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Mt. Sinai Medical Center, Miami (other)
• Locations: 1 site (Miami Beach, Florida)
• Trial ID: NCT03982693 on ClinicalTrials.gov

What this trial studies

TACT3a is a double blind, placebo-controlled, randomized trial designed to evaluate the effectiveness of edetate disodium-based chelation therapy in reducing cardiovascular events, including major amputations, in high-risk diabetic patients suffering from critical limb ischemia. The study will enroll 50 participants who will be randomly assigned to receive either the active chelation treatment or a placebo, with a treatment regimen consisting of 40 infusions over 30 weeks. Patients will be monitored for major cardiovascular endpoints over an average follow-up period of 1.25 years, with urine samples collected to assess metal levels before and after treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 50 and older with a history of diabetes and significant stenosis in the arteries of the affected limb.

Not a fit: Patients who do not have critical limb ischemia or those with less severe arterial blockages may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly reduce the risk of major cardiovascular events and amputations in diabetic patients with critical limb ischemia.

How similar studies have performed: Previous studies on chelation therapy have shown promising results, suggesting potential efficacy in similar patient populations.

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.

Where this trial is running

Miami Beach, Florida

• Mount Sinai Medical Center — Miami Beach, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Gervasio Lamas, MD — Icahn School of Medicine at Mount Sinai
• Study coordinator: Francisco Ujueta, MD

Conditions: Critical Limb Ischemia, Diabetes, Chelation