Diabetes, Myocardial Infarction
Conditions
Keywords
chelation
Brief summary
Trial to Assess Chelation Therapy 2 (TACT2) is a randomized, double blind controlled factorial clinical trial of edetate disodium-based chelation and high-dose oral vitamins and minerals to prevent recurrent cardiac events in diabetic patients with a prior myocardial infarction (MI).
Detailed description
The primary objective of TACT2, therefore, is to determine if the chelation-based strategy increases the time to the first occurrence of any of the components of the TACT2 primary endpoint: all-cause mortality, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina compared to the placebo chelation strategy. TACT2 is a 2x2 factorial trial testing 40-weekly edetate disodium-based chelation infusions and twice daily high-dose oral multivitamins and multiminerals (OMVM) in a placebo-controlled design. TACT2 is being carried out to replicate the findings of TACT1, which found a striking reduction of recurrent cardiovascular events in post-MI diabetic patients receiving edetate disodium-based chelation therapy.
Interventions
DRUGdisodium EDTA
IV Disodium Ethylene diamine tetra acetic acid in 500 cc
DIETARY_SUPPLEMENTOral Multi Vitamins/Minerals (OMVM)
6 tablets of Multi-vitamin/Multimineral daily
DRUGPlacebo disodium EDTA
IV Placebo comparator- 500 normal saline
DIETARY_SUPPLEMENTPlacebo Oral Multi Vitamins/Minerals (OMVM)
6 tablets of a placebo Multi-vitamin/Multimineral daily
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
National Heart, Lung, and Blood Institute (NHLBI)
Duke Clinical Research Institute
Mt. Sinai Medical Center, Miami
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age: ≥ 50 years 2. 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. 3. History of myocardial infarction based on the Universal Definition of MI. 1. When information about the MI hospitalization is available, all MI types except Type 2 qualify for study entry. 2. When information about the MI hospitalization is not available, a wall motion abnormality on imaging or a perfusion defect on scan that corresponds to a coronary distribution, whether or not accompanied by pathological Q waves in the appropriate distribution, will qualify the patient for study entry. This criterion requires a call to the CCC for case review.
Exclusion criteria
1. Baseline serum creatinine \>2.0 mg/dL. 2. HbA1C \>11%. 3. Myocardial infarction within 6 weeks of randomization. 4. History of allergic reactions to EDTA or any other components of the chelation solution, including heparin. Site personnel are to call the CCC to discuss heparin allergy. 5. Coronary or peripheral arterial revascularization procedure performed within the last 6 months. 6. Planned revascularization procedure in the 6 months following enrollment. 7. Heart failure hospitalization within 6 months prior to enrollment or in clinical heart failure at the time of proposed enrollment (such as NYHA Class 3 dyspnea + rales \>basilar, and additional signs of fluid overload). Such patients may be treated with diuretics and enrolled when stable. 8. Poor or no venous access in the upper extremities. 9. a. 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. b. Oral chelation therapy with an approved oral chelating agent within 2 years. 10. Prior participation in TACT. 11. Baseline platelet count \<100,000. 12. History of cigarette smoking within the last 3 months. 13. ALT or AST \> 2.0 times the upper limit of normal. 14. Wilson's disease, hemochromatosis, or parathyroid disease. 15. Any medical condition including a current diagnosis of cancer (except non-melanoma skin cancer) that will limit patient survival over the duration of the trial. 16. Any factor that suggests that the potential participant will not be able to adhere to the protocol. 17. Women of child-bearing potential including those with plans for post-menopausal in vitro fertilization or other reproductive technology.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Composite Outcome | 48 month follow-up (median) | Time to first event: myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Composite Outcome | 48 month follow-up (median) | Time to first event: myocardial infarction, stroke, or death from cardiovascular causes |
| Secondary Outcome | All-Cause Mortality was assessed through study completion, up to 48 months (median) | Time to All-Cause mortality |
Countries
United States
Participant flow
Recruitment details
A total of 1,000 patients were enrolled at 88 clinical centers from United States (83) and Canada (5). The first patient was enrolled on October 18, 2017 and the last patient on December 31, 2020. Each patient was randomly assigned to 1 of the 4 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Active/Active Active disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)
disodium EDTA
Oral Multi Vitamins/Minerals (OMVM) | 250 |
| Active/Placebo Active disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)
disodium EDTA | 249 |
| Placebo/ Active Placebo disodium EDTA (chelation) + Active Oral Multi Vitamins/Minerals (OMVM)
Oral Multi Vitamins/Minerals (OMVM)
Placebo disodium EDTA | 250 |
| Placebo/Placebo Placebo disodium EDTA (chelation) + Placebo Oral Multi Vitamins/Minerals (OMVM)
Placebo disodium EDTA
Placebo Oral Multi Vitamins/Minerals (OMVM) | 251 |
| Total | 1,000 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 46 | 34 | 35 | 43 |
| Overall Study | Lost to Follow-up | 17 | 18 | 16 | 11 |
| Overall Study | Withdrawal by Subject | 12 | 10 | 17 | 21 |
Baseline characteristics
| Characteristic | Active/Active | Active/Placebo | Total | Placebo/Placebo | Placebo/ Active |
|---|---|---|---|---|---|
| Age, Continuous | 66 years | 67 years | 67 years | 67 years | 67 years |
| Anterior MI location | 71 Participants | 73 Participants | 310 Participants | 86 Participants | 80 Participants |
| Aspirin, warfarin, or P2Y12 inhibitor | 223 Participants | 224 Participants | 897 Participants | 225 Participants | 225 Participants |
| Cadmium (urine) | 0.27 mcg/g | 0.33 mcg/g | 0.30 mcg/g | 0.28 mcg/g | 0.30 mcg/g |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants | 53 Participants | 198 Participants | 46 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 200 Participants | 191 Participants | 789 Participants | 201 Participants | 197 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 13 Participants | 4 Participants | 0 Participants |
| HDL | 41.0 mg/dL | 41.0 mg/dL | 41 mg/dL | 40.0 mg/dL | 42.0 mg/dL |
| Hemoglobin A1c | 7.3 % | 7.1 % | 7.2 % | 7.3 % | 7.3 % |
| LDL | 75.0 mg/dL | 72.0 mg/dL | 73 mg/dL | 73.0 mg/dL | 69.0 mg/dL |
| Lead (blood) | 9.80 mcg/L | 8.40 mcg/L | 9.2 mcg/L | 9.20 mcg/L | 9.50 mcg/L |
| Prior coronary revascularization | 209 Participants | 198 Participants | 813 Participants | 207 Participants | 199 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 11 Participants | 54 Participants | 16 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 22 Participants | 101 Participants | 26 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 6 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 3 Participants | 18 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 15 Participants | 38 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) White | 186 Participants | 194 Participants | 778 Participants | 194 Participants | 204 Participants |
| Region of Enrollment North America | 250 participants | 249 participants | 1000 participants | 251 participants | 250 participants |
| Sex: Female, Male Female | 61 Participants | 79 Participants | 270 Participants | 55 Participants | 75 Participants |
| Sex: Female, Male Male | 189 Participants | 170 Participants | 730 Participants | 196 Participants | 175 Participants |
| Statin | 210 Participants | 220 Participants | 852 Participants | 221 Participants | 201 Participants |
| Time from diabetes diagnosis to randomization | 13 years | 15 years | 14 years | 14 years | 15 years |
| Time from qualifying MI to randomization | 5 years | 5 years | 5 years | 5 years | 5 years |
| Triglycerides | 150.0 mg/dL | 134.0 mg/dL | 144.0 mg/dL | 149.0 mg/dL | 139.0 mg/dL |
| Type II Diabetes | 239 Participants | 242 Participants | 960 Participants | 244 Participants | 235 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 50 / 250 | 36 / 249 | 40 / 250 | 49 / 251 |
| other Total, other adverse events | 0 / 250 | 0 / 249 | 0 / 250 | 0 / 251 |
| serious Total, serious adverse events | 41 / 250 | 40 / 249 | 40 / 250 | 40 / 251 |
Outcome results
Primary
Primary Composite Outcome
Time to first event: myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or death from any cause
Time frame: 48 month follow-up (median)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active/Active | Primary Composite Outcome | 85 Participants |
| Active/Placebo | Primary Composite Outcome | 89 Participants |
| Placebo/ Active | Primary Composite Outcome | 90 Participants |
| Placebo/Placebo | Primary Composite Outcome | 86 Participants |
Secondary
Secondary Composite Outcome
Time to first event: myocardial infarction, stroke, or death from cardiovascular causes
Time frame: 48 month follow-up (median)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active/Active | Secondary Composite Outcome | 50 Participants |
| Active/Placebo | Secondary Composite Outcome | 40 Participants |
| Placebo/ Active | Secondary Composite Outcome | 55 Participants |
| Placebo/Placebo | Secondary Composite Outcome | 41 Participants |
Secondary
Secondary Outcome
Time to All-Cause mortality
Time frame: All-Cause Mortality was assessed through study completion, up to 48 months (median)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active/Active | Secondary Outcome | 50 Participants |
| Active/Placebo | Secondary Outcome | 36 Participants |
| Placebo/ Active | Secondary Outcome | 40 Participants |
| Placebo/Placebo | Secondary Outcome | 49 Participants |