Wednesday, February 6, 2008

Why was the diabetes study ACCORD halted?

Halting a major study is not something done quickly because it can mean a drastic loss of money for those funding the study. But recently a huge study (named ACCORD) on aggressively treating diabetes by greatly lowering the blood sugar levels, greatly lowering the cholesterol and trigycerides and also blood pressure was halted.

The news stories were indefinite about why the study was halted and what WERE those treatments which proved to be too risky. I decided to research it.

First, I found that ACCORD has a website although nothing on there about halting the study!

I was curious about the treatments which turned out to be MORE dangerous than the standard treatment. From the protocol PDF, I found:

For blood sugar control: control group: metformin, and for the experimental group: glipozide and injected insulin (as an aggressive way to greatly lower A1C)

Lowering cholesterol and trigycerides: for the experimental group: higher doses of Zocor combined with fenofibrate (Tricor) and they did express some concern about the "adverse events" going in:

Because 40 mg of simvastatin may increase the risk for adverse events, particularly in the patients receiving fenofibrate, participants will be followed closely and CPK regularly measured.

The control group was just given Zocor. The experimental part was mixing Tricor with higher doses of Zocor. From websites on Tricor, I found the following general warnings:

Before taking fenofibrate, tell your doctor if you have
· liver disease,
· biliary cirrhosis,
· kidney disease,
· gallbladder disease,
· hypothyroidism (an underactive thyroid gland), or
· diabetes.

Fenofibrate apparently interacts adversely with the statin drugs and therein one suspects, lay one problem of this study:

Before taking fenofibrate, tell your doctor if you are taking any of the following medicines:
· an anticoagulant (blood thinner) such as warfarin (Coumadin);
· cyclosporine (Neoral, Sandimmune);
· lovastatin (Mevacor), simvastatin (Zocor), pravastatin (Pravachol), fluvastatin (Lescol), atorvastatin (Lipitor), or cerivastatin (Baycol); or
· cholestyramine (Questran) or colestipol (Colestid).
• You may not be able to take fenofibrate, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the drugs listed above.
• Drugs other than those listed here may also interact with fenofibrate. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

On another website, there are extensive lists of medications which can interact adversely with Tricor.

According to the ACCORD website, ACCORD was heavily funded by pharmaceuticals:

Abbott Laboratories (and Fournier Laboratories)
AstraZeneca LP
Aventis Pharmaceuticals, Inc.
GlaxoSmithKline Pharmaceuticals
King Pharmaceuticals, Inc.
MediSense Products (Division of Abbott Laboratories)
Merck & Company, Inc.
NetGroup Diabetic Services
Novartis Pharmaceuticals, Inc.
Novo Nordisk Pharmaceuticals, Inc.
Omron Healthcare, Inc.
According to one blog, the intensive treatment group (the experimental group) had more deaths than the controls:

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study enrolled 10,251 participants. Of these, 257 in the intensive treatment group have died, compared with 203 within the standard treatment group.

The researchers stated they did not know why they had a higher death toll in the "intensive treatment" group.

The interesting thing about this is that if you read the protocol PDF, on paper, their ideas seemed well based in former studies and logic. And yet, in reality that wasn't the case at all.

My suspicions are it had something to do with mixing the statin (zocor) with fenofibrate since on the fenofibrate website, that's in the warnings as a definite "no no".

The fact that the news stories about the study were so indefinite about the nature of the treatments, intrigued me enough to research it further...

Mystery kind of solved.