1 / 52

TACT T rial to A ssess C helation T herapy

TACT T rial to A ssess C helation T herapy. Principal Investigator Gervasio A. Lamas, MD Mt. Sinai Hospital; Miami Beach, FL. TACT Sponsors and Institutional Participants. NIH—National Institutes of Health NCCAM—National Center for Complementary and Alternative Medicine

jonathanhall
Download Presentation

TACT T rial to A ssess C helation T herapy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. TACTTrial to Assess Chelation Therapy Principal Investigator Gervasio A. Lamas, MD Mt. Sinai Hospital; Miami Beach, FL

  2. TACT Sponsors and Institutional Participants • NIH—National Institutes of Health • NCCAM—National Center for Complementary and Alternative Medicine • NHLBI—National Heart, Lung and Blood Institute • Other Participating Institutions • Duke Clinical Research Institute (Data Coordinating Center and QOL Data • Brigham and Women’s Hospital (Boston) Clinical Events Committee • Others

  3. Basic Features of TACT Study • 30 Million Dollar Study • Study to be conducted at approximately 100 Sites • Study to be conducted over a 5-year period • It is a randomized, double-blind, placebo controlled study • Will test the value of chelation therapy and high dose oral vitamins and minerals for coronary artery disease

  4. TACT Rockland County Site Schachter Center for Complementary Medicine 2 Executive Boulevard; Suite 202 Suffern, NY 10901 Phone 845-368-4700; FAX 845-368-4727 Website: www.schachtercenter.com E-Mail: office@mbschachter.com

  5. TACT at the Schachter Center • Primary Investigator • Michael B Schachter MD, CNS, FACAM • Clinical Coordinator • Sally Minniefield RN, PAC • Assistant Clinical Coordinator • Dolores Tritico RN

  6. Specific Aims • To determine whether chelation or high-dose supplements in patients with CHD will reduce the incidence of clinical cardiovascular events; • To determine whether chelation and high-dose supplements have acceptable safety profiles.

  7. Why is TACT Being Done? • Raging controversy over the value of chelation therapy for treating coronary artery disease • More than a thousand physicians have used chelation therapy to treat coronary artery disease • It has been used for more than 40 years • Most of these physicians and the patients receiving the treatment think that it is effective • However, mainstream medicine regards it as unproven and discourages patients from receiving the treatment

  8. NIH Wishes to Settle the Controversy • If chelation therapy safe and effective, • then, many more should receive the treatment • and insurance should cover the treatment • If chelation therapy worthless, • then, people with coronary artery disease should stop wasting their time and money • and insurance companies should continue to refuse to pay • Therefore, a well designed clinical study is necessary

  9. What is Coronary Artery Disease? • Most common form of heart disease • Arteries that carry oxygen and nutrients to the heart get blocked with plaque (fatty substances and calcium salts) • Less oxygen and nutrients reach heart muscle, leading to: • Angina Pectoris-Pain in the chest • Heart Attack or Myocardial Infarction

  10. How Important is Coronary Artery Disease (CAD)? • Most frequent cause of death and morbidity in the United States • 7 million Americans suffer from CAD • More than 500,000 Americans die from CAD each year

  11. What are Risk Factors for Coronary Artery Disease? • High blood pressure • High cholesterol levels-Especially high LDL and low HDL • Smoking • Obesity • Physical inactivity • Diabetes • Family history of CAD • Gender-Increased in men compared to premenopausal women of comparable age • Age-Risk increases with age

  12. How is Coronary Artery Disease (CAD) Diagnosed? • Symptoms-e.g chest pain on exertion, shortness of breath • Blood tests that help to determine if a heart attack has occurred • Electrocardiogram (may do with stress test) • Echocardiogram • Imaging studies (e.g thallium scans and angiograms)

  13. How is Coronary Artery Disease Treated in the United States? • Conventional treatment includes: • Lifestyle modification (dietary changes and exercise) • Medication (ASA, Beta Blockers, ACE Inhibitors, etc) • Invasive interventions (Bypass, Balloon angioplasty, Stents • Despite these “proven” treatments, a national survey reveals that 1/3 of patients seek alternative therapies, including EDTA chelation therapy

  14. What is Chelation? • Greek word chelos meaning claw • Refers to an organic molecule binding a mineral tightly • Examples: chlorophyll is a chelate of magnesium and hemoglobin is a chelate of iron • EDTA is a synthetic amino acid capable of binding to lead, cadmium and other toxic metals, as well as calcium

  15. Chelating Agents and Chelation Therapy • Many chelating agents • EDTA is a chelating agent approved by the FDA to remove lead from the body • Chelation therapy involves administering a chelating agent for the purpose of removing a toxic mineral from the body • Removal of toxic minerals may help coronary artery disease because there is evidence that toxic minerals may play a role in coronary artery disease

  16. Brief History of EDTA Chelation Therapy • 1950’s-EDTA found to be useful to treat lead poisoning • Dr. Clark in the 1950’s reasoned that since EDTA is also capable of binding calcium and calcium is found in the clogged arteries in the plaque, perhaps EDTA could be used to treat coronary artery disease • Initial clinical observations were very promising and several papers were published supporting its use • Three small randomized placebo controlled studies in recent years failed to show benefits • Controversy rages over whether or not it is beneficial

  17. Technique for EDTA Chelation Therapy for CAD • Disodium EDTA is a synthetic amino acid • Chelates or binds heavy metals and calcium • Intravenous infusion given for 3 hours • Administered in MD’s office once a week, usually for 30 to 50 treatments • Magnesium, potassium, vitamins B6, C, heparin and other components added to infusion

  18. EDTA Chelation Therapy for CAD is Part of Full Program • Part of a total program that involves diet, supplements, exercise, stress management and medication • Depletes trace minerals, so these must be replaced with good diet, oral & IV minerals • Side effects minimal when the ACAM protocol is followed

  19. Proposed Mechanisms for How Chelation Therapy Works • Reduces free radicals • Removes toxic minerals, such as lead and cadmium, which may contribute to CAD • Removes soft tissue calcium • Others

  20. Possible Side Effects of Properly Given EDTA Chelation Therapy • Generally side effects are few and not serious • Most common is irritation at the site of infusion • Rare side effects can include: • Fever • Low blood pressure • Low serum • Headache • Nausea and vomiting • Injury to the kidneys • Others, but extremely

  21. Examples of Published Studies Claiming Benefits • Danish study • Brazilian study • Meta-analysis • Review article by Dr. Schachter

  22. Reducing CV Surgical Intervention With Mg-EDTA • Retrospective Danish study involving 470 CV patients involving many parameters • 80—91% improved from baseline depending on parameter used • Waiting list for CABG or amputation • 58/65 did not need CABG after chelation • 24/27 did not need amputation after chelation Hancke C & Flytlie K. Journal of Advancement in Medicine, Vol. 6, Number 3, Fall 1993, 161-171.

  23. EDTA For Heart, Peripheral and Brain Circulation • Brazilian retrospective study involving 2,870 patients with CV and other diseases • Objective criteria used • 98% peripheral CV showed marked or good • 93% coronary CV showed marked or good • 60% cerebro CV showed marked or good Olszewer, E & Carter JP. Medical Hypothesis, 27, 1988, 41-49.

  24. Meta-analysis Of EDTA Chelation For CV Disease • Review of 19/40 articles involving 22,765 patients that met criteria to measure effects of EDTA on CV disease • Correlation coefficient of 0.88 suggesting a high positive relationship between EDTA therapy and improved CV function • 87% of patients improved Chappell LT & Stahl JP. Journal of Advancement in Medicine, Vol.6, No.3, Fall 1993, 139-159.

  25. Review Article on EDTA Chelation Therapy • “Overview, historical background and current status of EDTA chelation therapy for atherosclerosis” • Reviews of scientific studies, clinical reports • Analysis of controversies Schachter MB, Journal of Advancement in Medicine, Vol.9, No.3, Fall 1996, 159-177.

  26. Criticism of Positive Articles on Chelation Therapy • Published in journal of organization that promotes EDTA chelation therapy and teaches it to physicians • All authors are strong proponents of chelation therapy and may be biased • Studies not randomized, double-blind or placebo controlled • For these and other reasons, most conventional clinicians are skeptical and think the treatment is at best unproven

  27. NCCAM View of EDTA Chelation Therapy Evidence for CAD-1 • Bulk of the evidence supporting EDTA chelation therapy is in the form of case reports and case series. • Approximately 12 published descriptive studies and 5 randomized controlled clinical trials regarding the use of EDTA chelation for CAD. • Although each descriptive study did report a reduction in angina, they were uncontrolled clinical observations or retrospective data, typically with a small number of participants.

  28. NCCAM View of EDTA Chelation Therapy Evidence for CAD-2 • Of the five clinical trials in which patients were randomly selected to receive chelation therapy or a placebo (a dummy solution), the most rigorous way of assessing a new treatment, three trials involved so few people that only a dramatic improvement could have been detected. Studies need larger number of participants to detect more mild benefits of a treatment. • The fourth study was never published in final form, so its conclusions are uncertain. • Finally, the fifth study reported that EDTA chelation was associated with an improvement in ability to exercise, but it had only 10 participants.

  29. TACT’s Attempt to Settle the Question • Multicenter study involving as many as 100 sites or more • Some sites are run by chelation proponents and others by conventional cardiologists or other conventional MDs, who are skeptical • Study is randomized, double-blind and placebo controlled

  30. TACT Design • 5-year randomized, double-blind, placebo-controlled; • 2X2 factorial trial; • Testing the standard chelation solution versus placebo; • Testing the effects of a high-dose antioxidant vitamin and mineral supplementation, versus placebo.

  31. Specific Aims • To determine whether chelation or high-dose supplements in patients with CHD will reduce the incidence of clinical cardiovascular events; • To determine whether chelation and high-dose supplements have acceptable safety profiles.

  32. Details of TACT Trial: Factorial Design—Two Trials in One • Total number of patients 2,372 • Half (1,186) get chelation and half get placebo • Half of each group above (593) will get oral high dose vitamin and mineral supplements (6 pills) and half of each group will get oral placebo that looks like high dose vitamin and mineral • All participants will receive a single vitamin- mineral pill containing: B6, Zinc, Manganese, Copper and Chromium

  33. Primary Endpoint • Composite clinical endpoint including: • all cause mortality • myocardial infarction • stroke • coronary revascularization • hospitalization for angina

  34. Secondary Endpoints • Composite serious irreversible vascular events including: cardiovascular death, or non-fatal MI or non-fatal stroke.

  35. Substudy Specific Aims Two substudies will be conducted whose specific aims are as follows: • To determine whether chelation or high-dose supplements improve quality of life; • To conduct an economic analysis of chelation therapy and high dose supplements.

  36. Quality of Life Endpoints Baseline Questionnaire on every randomized patient administered by the Site Coordinator Follow-up Questionnaire on 1000 randomized subset by DCRI telephone at 6, 12 and 24 months • Cardiac physical functioning: Duke Activity Status Index • Psychological well-being: SF-36 MHI5 • Angina symptoms from Seattle Angina Questionnaire • Patient utilities: EuroQoL • Analysis by intention to treat

  37. Timeline • First patient enrolled September 2003. • Enroll for 3 years. • Follow patients until August 2007. • Trial ends in November 2007.

  38. Inclusion Criteria • Men or women age 50 and older • MI >6 weeks prior to randomization T A C T

  39. Definition of MI • Biomarkers + (symptoms or ECG changes) OR • Imaging evidence of myocardial scar + evidence of coronary disease on angiography. This requires PI involvement, especially the decision that the CAD corresponds to an imaged scar. Remember that the CCC is always happy to help.

  40. Major Exclusion Criteria-1 • Chelation within 5 years • Known allergy to any components of solutions or vitamins (heparin may be omitted from the infusion) • Carotid or coronary revascularization within 6 months, or planned revascularization • Symptomatic HF, or HF hospitalization within 6 months

  41. Major Exclusion Criteria-2 • Uncontrolled hypertension (BP>160/100) • No venous access • Creatinine >2.0mg/dL • Baseline platelets <100,000 • Cigarette smoking within 3 months

  42. Study Interventions • ACAM protocol EDTA chelation vs placebo • High dose antioxidant vitamins and minerals vs placebo

  43. Chelation Solution Chelation placebo solution is 500 ml 500cc of 0.9N NaCl, and 1.2% dextrose

  44. Pharmacy – Delivery of Study Drugs • Infusion Kits – UPS delivery the morning before scheduled visit • 500 ml bag IV solution • 2 - 20ml syringes • Vitamins – Initial supply shipped with first kit • Subsequent shipments every two months • Subsequent shipments contain 2-month supply (360 tablets in a bottle; 60 gel-caps in blister packs) • After the completion of the 40th infusion, shipments will be done on a quarterly basis.

  45. Pharmacy – Simple Mixing Instructions • Prepare infusion just prior to administration • Inject 2 syringes of solution into IV bag using 21 g needles • Allow solution to reach room temp prior to infusing (30 minutes) • Administer within 24 hrs of mixing

  46. Drug Shipment

  47. Blinding the Therapy

  48. Non-Study Interventions • Up to date guidelines for medical management of post-MI patients including statins, aspirin, beta-blockers, and ACE inhibitors. 

  49. Study Overview • Screening and Randomization • Perform initial screening • Obtain informed consent • Submit lab samples • Complete screening worksheet • Administer EQOL Baseline Questionnaire • Review lab results for eligibility • Randomize via TrialMaster

  50. Study Overview • Infusion Visits • Initial - Weekly X 30 wks • Maintenance - Every 2 – 8 weeks • Enter data into TM during or immediately post visit

More Related