Critical Limb IschemiaPhase 3TACT3aNCT03982693
Trial to Assess Chelation Therapy in Critical Limb Ischemia
A Phase 3 study testing Edetate Disodium in people with Critical Limb Ischemia and Diabetes, run by Mt. Sinai Medical Center, Miami at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Critical Limb Ischemia, Diabetes
- What is being tested?
- Edetate Disodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Mar 2019to Jul 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- <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.
Show all 23Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mount Sinai Medical Center
Miami Beach, Florida, 33140
About this study
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.
Read the detailed description
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.
The study plans to enroll 50 patients with diabetes and critical limb ischemia (CLI) to prevent the major cardiovascular endpoints of major amputation, coronary revascularization, stroke, Myocardial Infarction (MI), or death (all-cause) during an average 1.25 years of follow-up. Patients will be randomly assigned to chelation or placebo with a 3:2 (30 active, 20 placebo) allocation ratio. Treatment will consist of 40 active or placebo infusions over 30 weeks. Active therapy will be the same edetate disodium-based infusion used safely and successfully in a previous published study, Trial to Assess Chelation Therapy (TACT). Baseline and post infusion urine metals will be collected. Following the final infusion, patients will be contacted quarterly until the end of the study.
- Conditions
- Critical Limb Ischemia, Diabetes
- Being tested
- Edetate Disodium, Placebo
- Keywords
- Chelation, Critical Limb Ischemia, Diabetes
- Medical subject headings
- Chronic Limb-Threatening Ischemia, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Edetate DisodiumDrug
Also called TACT EDTA infusion
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.
PlaceboOther
Placebo infusions consist of 500 ml normal saline.
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | edetate disodium (EDTA)dff active infusion Receives: Drug: Edetate Disodium |
| Placebo | Placebo comparator | Placebo infusion Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevention of major cardiovascular endpoints
Major cardiovascular endpoints include: coronary revascularization, stroke, MI, death (all-cause), or major amputation
Measured: 3 years (average follow-up 1.25 years)
Secondary outcomes (9)
Amputations
- Major amputations due to vascular disease. Major amputations are defined as any procedure that results in amputation at the level above the ankle. 49, 50
- Total amputations due to vascular disease
Measured: 3 years (average follow-up 1.25 years)
Heart failure
- Heart failure hospitalizations or prolonged (>12 hours) ER stay for heart failure
Measured: 3 years (average follow-up 1.25 years)
Changes in Pain severity
- Any changes in pain will be recorded at baseline, infusions 10, 20, 40 (or final), and end of study recorded using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference- Short Form 8a. The scale range is 1 to 5, with 1 being the best outcome (no pain interference) and 5 the worse (very much interference)
Measured: 3 years (average follow-up 1.25 years)
Urine Metals
- Changes in urine metal levels measured at the Metals Core Lab and measured at baseline and infusion 40 (or final).
Measured: 1 year
Changes in Quality of Life
- Health-related quality of life (QOL) changes recorded at baseline, 10, 20, 40 (or final), and end of study using the 36-Item Short Form Health Survey (SF-36 v2). The 36 questions assess eight health-related concepts: physical functioning, role limitations due to physical health problems (role physical), bodily pain, general health, energy levels/fatigue (vitality), social functioning, role limitations due to emotional problems (role emotional), and psychological distress (mental health). The scales vary depending on the question asked.The survey will be used to detect change (better or worse) in participants' health state over the course of the study.
Measured: 3 years (average follow-up 1.25 years)
Wound Severity
Wound severity (quantified and imaged with HIPAA-compliant photography) photographed at baseline 10, 20, 40 (or final), and end of study
Measured: 3 years (average follow-up 1.25 years)
Changes in skin perfusion pressure in the ankle
- Changes in skin perfusion pressure will be measured at 10, 20, 40 (or final), and end of study, using the ankle-brachial index (mmHg)
Measured: 3 years (average follow-up 1.25 years)
Changes in skin perfusion pressure in the toe
- Changes in skin perfusion pressure will be measured at 10, 20, 40 (or final), and end of study, using the toe-brachial index (mmHg).
Measured: 3 years (average follow-up 1.25 years)
Changes in PAD Quality of Life
- PAD related quality of life (QOL) changes recorded at baseline, 10, 20, 40 (or final), and end of study using the Peripheral Artery Questionnaire (PAQ), which is a 20-item questionnaire measuring physical limitations, symptoms, symptom stability, treatment satisfaction, quality of life, and social function. The scales vary depending on the question asked. The survey will be used to detect change (better or worse) in participants responses over the course of the study.
Measured: 3 years (average follow-up 1.25 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2019
- Study start19 Mar 2019
- Primary completionDec 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Critical Limb IschemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mt. Sinai Medical Center, Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gervasio Lamas, MD, Mt. Sinai Medical Center, Miami
- Investigators
- Gervasio Lamas, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03982693
- Sponsor's protocol ID
- 19-05-H-01
- Acronym
- TACT3a
- Status last verified
- Jun 2026
- First submitted
- 27 May 2019
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 28689036Lamas 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.
PubMed 22172430Escolar 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.
PubMed 24254885Ujueta 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.
PubMed 30152247Ujueta 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.
PubMed 31101487
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial to Assess Chelation Therapy in Critical Limb Ischemia
- ClinicalTrials.gov ID
- NCT03982693
- Acronym / sponsor ID
- TACT3a / 19-05-H-01
- Conditions
- Critical Limb Ischemia, Diabetes
- Keywords
- Chelation, Critical Limb Ischemia, Diabetes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Mt. Sinai Medical Center, MiamiUniversity, hospital or other
- Study start
- 19 Mar 2019 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 11 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
The study plans to enroll 50 patients with diabetes and critical limb ischemia (CLI) to prevent the major cardiovascular endpoints of major amputation, coronary revascularization, stroke, Myocardial Infarction (MI), or death (all-cause) during an average 1.25 years of follow-up. Patients will be randomly assigned to chelation or placebo with a 3:2 (30 active, 20 placebo) allocation ratio. Treatment will consist of 40 active or placebo infusions over 30 weeks. Active therapy will be the same edetate disodium-based infusion used safely and successfully in a previous published study, Trial to Assess Chelation Therapy (TACT). Baseline and post infusion urine metals will be collected. Following the final infusion, patients will be contacted quarterly until the end of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Drug: Edetate Disodiumedetate disodium (EDTA)dff active infusion |
| Placebo | Placebo comparator | Other: PlaceboPlacebo infusion |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- Not a candidate or a failed candidate for surgical or transcatheter revascularization;
Key exclusion criteria (23 listed)
- <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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Edetate DisodiumAlso: TACT EDTA infusionThe 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. | Drug | Active |
| PlaceboPlacebo infusions consist of 500 ml normal saline. | Other | Placebo |
Primary outcome
Prevention of major cardiovascular endpoints
Time frame: 3 years (average follow-up 1.25 years)
Major cardiovascular endpoints include: coronary revascularization, stroke, MI, death (all-cause), or major amputation
9 secondary outcomes
Amputations
Time frame: 3 years (average follow-up 1.25 years)
Heart failure
Time frame: 3 years (average follow-up 1.25 years)
Changes in Pain severity
Time frame: 3 years (average follow-up 1.25 years)
Urine Metals
Time frame: 1 year
Changes in Quality of Life
Time frame: 3 years (average follow-up 1.25 years)
Wound Severity
Time frame: 3 years (average follow-up 1.25 years)
Changes in skin perfusion pressure in the ankle
Time frame: 3 years (average follow-up 1.25 years)
Changes in skin perfusion pressure in the toe
Time frame: 3 years (average follow-up 1.25 years)
Changes in PAD Quality of Life
Time frame: 3 years (average follow-up 1.25 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Background: PubMed 28689036Arenas 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.
- Background: PubMed 22172430Lamas 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.
- Background: PubMed 24254885Escolar 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.
- Background: PubMed 30152247Ujueta 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.
- Background: PubMed 31101487Ujueta 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.
Related trials for Critical Limb Ischemia
RecruitingObservational study
miRNAs in Critical Limb Ischemia (miRNACLI)
Critical Limb Ischemia
Active, not recruitingObservational study
Laser Atherectomy and Sirolimus-eluting Balloon Angioplasty for CLTI
Chronic Limb Threatening Ischemia
Recruiting
Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease
Peripheral Artery Disease, Diabetes Mellitus
RecruitingObservational study
Vessel Recoil in Specific CLTI Populations
Chronic Limb Threatening Ischemia
Not yet recruiting
DCB Outcomes After Non-Compliant Balloon Vessel Preparation With or Without Scoring in Patients With Femoropopliteal Arterial Disease
Femoropopliteal Disease, Drug Coated Balloon
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gervasio Lamas, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Edetate Disodium in people with Critical Limb Ischemia and Diabetes, run by Mt. Sinai Medical Center, Miami at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevention of major cardiovascular endpoints (time frame: 3 years (average follow-up 1.25 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03982693, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.