TACT Principal Investigator Reflects On A Long And Contentious Journey Reply

In a fascinating and important blog post, Gervasio Lamas offers a deeply personal perspective on the long and contentious journey of the Trial to Assess Chelation Therapy (TACT), for which he was the principal investigator.

gervasio-lamasHere are a few quotes from his post, but I can’t urge you strongly enough to read the entire post over on CardioExchange. (Click here for my brief summary of TACT.)

Changing minds is difficult. Unexpected results meet resistance. Out of the mainstream research is subject to heavy criticism. I guess I knew all these truisms when we embarked on the Trial to Assess Chelation Therapy (TACT). Still, I thought we were answering an important clinical question.

To say that this trial was controversial is an understatement. I had previously worked peacefully in other clinical trials, worrying about enrollment, about the DSMB, and about interpretation of data. Not so, here. In retrospect, I had always thought that the adversaries to this study would be the chelation practitioners. After all, they were using an unproven therapy. Why would they want us to show it did not work?

The opposite was true. The chelation practitioners and their main professional organization, the American College for Advancement in Medicine, helped us at every turn. They felt they were doing good, and that bringing chelation to the crucible of a clinical trial would lead to many more patients being helped.

In fact, the principal obstructionists were groups of self-appointed anti-chelation “experts”, who had never administered chelation, had never designed or run clinical trials, but who knew how to make noise and recruit media to their dubious cause – that scientific thought should not be brought to bear on the question of whether chelation was safe and effective.

The gist of the objections to the trial, once legitimate methodological concerns were addressed, was an outcry that, because cardiologists believed that EDTA was quackery, the study had to be negative. Therefore we had done something wrong. Just imagine if this had been stem cells or a new anti-platelet: Kudos all the way, right? Humble chelation got heckles and hecklers. I told my dean at Columbia that people were very upset because they did not like the results. He said “That’s why you do research.”

So now what? Do we recommend chelation? This is where the cautious scientist has to take control. We reported a subgroup, and we have been fooled by subgroups before, so more research has to take place before all of us can jump on this bandwagon.

 

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TACT Substudy Suggests Possible Strong Benefit for Chelation in Diabetics Reply

One year ago the results of the TACT trial were published in JAMA, sparking an enormous controversy over the propriety of publishing a trial suggesting that chelation therapy might be beneficial in people with cardiovascular disease. Chelation therapy has long been a staple of alternative medicine, but until the publication of TACT it had received no credit whatsoever in mainstream medicine. TACT was supported by the NIH as part of an initiaitve to test the scientific basis of alternative medical therapies.

The JAMA paper reported positive results for the prespecified subgroup of patients who had diabetes at the start of the trial. Now a new paper, presented at the American Heart Association Scientific Sessions and published online in Circulation: Cardiovascular Quality and Outcomes, focuses on this important subgroup, and provides even stronger evidence for a possible benefit for chelation in patients with diabetes. The authors speculate that ethylene diamine tetra-acetic acid (EDTA) chelation might have an effect on metal-catalyzed oxidation reactions in the development of advanced glycation end-products, which appear to play a central role in diabetic complications.

The primary endpoint of the main trial – the composite of death, MI, stroke, coronary revascularization, or hospitalization for angina – was significantly lowered from 30% in the placebo group to 26% in the chelation group (HR 0.82, 0.69-0.99, p=0.035).

Click here to read the full post on Forbes.

 

NIH Trial Gives Surprising Boost To Chelation Therapy 3

With a result that is likely to surprise and baffle much of the mainstream medical community, a large NIH-sponsored trial has turned up the first substantial evidence in support of chelation therapy for patients with coronary disease.  Known as TACT (Trial to Assess Chelation Therapy),  the highly controversial trial was presented today at the AHA by Gervasio Lamas. The trial was sponsored by two NIH institutes, the National Center for Complementary and Alternative Medicine and the National Heart Lung and Blood Institute.

Chelation therapy with EDTA to remove heavy metals from the blood in order to treat coronary disease has been around– and provoked criticism– since the 1950s. Despite a lack of evidence and the skepticism of the medical community, passionate supporters have kept the therapy alive in alternative medicine circles.

TACT was funded by the NIH more than a decade ago as part of a much-publicized initiative to study the claims of alternative medicine. In 2008 enrollment in TACT was temporarily suspended in response to claims that the trial was unethical. The trial was additionally hampered by slow enrollment.

Now the results of TACT will likely provide ammunition to chelation defenders, but the trial investigators and other experts have expressed considerable caution about the proper interpretation of the results.

TACT was a double blind study testing active or placebo infusions of chelation in stable patients with a history of MI. Due to slow enrollment the trial was downsized, ultimately enrolling 1,708 patients instead of the planned 2,372 patients. To maintain the trial’s power to achieve a meaningful result the follow-up time was increased. Because of the this change, and because the data and safety monitoring board reviewed the data multiple times over the course of the study, the threshold for statistical significance was lowered to 0.036.

The primary endpoint of the trial– the composite of death, MI, stroke, coronary revascularization, or hospitalization for angina– was significantly lowered in the chelation group:

  • 26.5% in the chelation group versus 30% in the placebo group (HR 0.82, 0.69-0.99, p=0.035)

There were no significant differences in any of the individual components of the primary endpoint. Most of the difference between the groups was due to a lower rate of coronary revascularization in the chelation group:

  • 15.5% versus 18.1% (HR 0.81, CI 0.64-1.02, p=0.076)

Nearly all the benefit in the trial was found to occur among the one-third of patients in the trial who had diabetes:

  • 102 events versus 67 events (HR 0.61, CI 0.45-0.83, p=0.002)

The investigators were cautious in their interpretation, noting that the trial barely achieved statistical significance, most of the difference was found in the softer endpoint of revascularization, and the finding is less reliable since there was a high withdrawal rate (17%) of patients in the trial.

The authors said their findings were “unexpected and additional research will be needed to confirm or refute our results and explore possible mechanisms of therapy.” TACT, they concluded, “does not constitute evidence to recommend the clinical application of chelation therapy.”

At an AHA press conference, Paul Armstrong said that TACT was a response to an unusual situation. On the one hand, most physicians and scientists have dismissed chelation therapy as lacking any evidence or rationale. On the other hand, chelation therapy is strongly supported by the alternative medicine community and more than 100,000 people receive chelation therapy each year. Armstrong said the results of the trial were “hypothesis generating, not practice changing.”
Click here to read the AHA press release…