Trial to Assess Chelation Therapy in Critical Limb Ischemia

NCT03982693 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 19-05-H-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Critical Limb Ischemia; Diabetes

Keywords

Chelation; Critical Limb Ischemia; Diabetes

Outcome Measures

Primary Outcomes (1)

• Prevention of major cardiovascular endpoints

  Major cardiovascular endpoints include: coronary revascularization, stroke, MI, death (all-cause), or major amputation

  3 years (average follow-up 1.25 years)

Secondary Outcomes (9)

• Amputations

  3 years (average follow-up 1.25 years)

• Heart failure

  3 years (average follow-up 1.25 years)

• Changes in Pain severity

  3 years (average follow-up 1.25 years)

• Urine Metals

  1 year

• Changes in Quality of Life

  3 years (average follow-up 1.25 years)

Study Arms (2)

Active

ACTIVE COMPARATOR

edetate disodium (EDTA)dff active infusion

Drug: Edetate Disodium

Placebo

PLACEBO COMPARATOR

Placebo infusion

Other: Placebo

Interventions

Edetate Disodium DRUG

The solution contains up to 3 g of edetate disodium adjusted based on creatinine clearance, 2 g of magnesium chloride, 100 mg of procaine hydrochloride, 2500 U of heparin, 7 g of ascorbate, 2 milliequivalent (mEq) potassium chloride (KCl), 840 mg sodium bicarbonate, 250 mg pantothenic acid, 100 mg of thiamine, 100 mg of pyridoxine, and sterile water to complete 500 mL.

Also known as: TACT EDTA infusion

Active

Placebo OTHER

Placebo infusions consist of 500 ml normal saline.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \<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

Sponsors & Collaborators

• Mt. Sinai Medical Center, Miami: lead

Study Sites (1)

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

RECRUITING

Related Publications (5)

• Arenas IA, Navas-Acien A, Ergui I, Lamas GA. Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion. Environ Res. 2017 Oct;158:443-449. doi: 10.1016/j.envres.2017.06.039. Epub 2017 Jul 6.

  PMID: 28689036 BACKGROUND

• Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL, Drisko JA, Lee KL. Design of the Trial to Assess Chelation Therapy (TACT). Am Heart J. 2012 Jan;163(1):7-12. doi: 10.1016/j.ahj.2011.10.002.

  PMID: 22172430 BACKGROUND

• Escolar E, Lamas GA, Mark DB, Boineau R, Goertz C, Rosenberg Y, Nahin RL, Ouyang P, Rozema T, Magaziner A, Nahas R, Lewis EF, Lindblad L, Lee KL. The effect of an EDTA-based chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the Trial to Assess Chelation Therapy (TACT). Circ Cardiovasc Qual Outcomes. 2014 Jan;7(1):15-24. doi: 10.1161/CIRCOUTCOMES.113.000663. Epub 2013 Nov 19.

  PMID: 24254885 BACKGROUND

• Ujueta F, Arenas IA, Diaz D, Yates T, Beasley R, Navas-Acien A, Lamas GA. Cadmium level and severity of peripheral artery disease in patients with coronary artery disease. Eur J Prev Cardiol. 2019 Sep;26(13):1456-1458. doi: 10.1177/2047487318796585. Epub 2018 Aug 28. No abstract available.

  PMID: 30152247 BACKGROUND

• Ujueta F, Arenas IA, Escolar E, Diaz D, Boineau R, Mark DB, Golden P, Lindblad L, Kim H, Lee KL, Lamas GA. The effect of EDTA-based chelation on patients with diabetes and peripheral artery disease in the Trial to Assess Chelation Therapy (TACT). J Diabetes Complications. 2019 Jul;33(7):490-494. doi: 10.1016/j.jdiacomp.2019.04.005. Epub 2019 Apr 14.

  PMID: 31101487 BACKGROUND

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Diabetes Mellitus

Interventions

Pentetic Acid

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids

Study Officials

• Gervasio Lamas, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francisco Ujueta, MD

CONTACT

305-674-2162; Francisco.Ujueta@msmc.com

Beatriz Acevedo

CONTACT

305-674-2162; Beatriz.Acevedo@msmc.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: June 11, 2019
• Study Start: March 19, 2019
• Primary Completion: December 1, 2024
• Study Completion: July 1, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08

Locations

US (1)