Two Sites Resign from Avandia TIDE Clinical Trial

May 23, 2010, 6:00AM. By Gordon Gibb

Winston-Salem, NCWhile the makers of Avandia continue to defend their product against allegations of heart attack, liver failure and other adverse effects, a clinical trial designed to determine the safety and efficacy of Avandia once and for all is going through some turbulent waters. In the meantime, the US Food and Drug Administration (FDA) will host a July summit to discuss the future of a clinical trial for the type 2 diabetes drug.

As revealed in the 5/21/10 edition of the News Observer of North Carolina and reported the day prior by the Wall Street Journal, two potential sites for the TIDE clinical trial have pulled out due to a lack of suitable candidates. One of those sites is Wake Forest University Baptist Medical Center in Winston-Salem. The decision to decline participation in the study was reportedly unrelated to any safety concerns.

The TIDE trial involves about 170 sites worldwide and 21 sites in the US. Besides Wake Forest, the only other site designated for the TIDE trial in North Carolina is Duke University Medical Center. Mary Furst, a clinical researcher there, said that Duke is continuing to recruit patients for the trial, although it has been a challenging process. "Has it become more difficult? Sure," she said.

The TIDE trial is designed to compare Avandia with Actos, a competing type 2 diabetes drug deemed by many as a safer alternative. GlaxoSmithKline, based in the UK, contests that assertion, and is continuing with the TIDE trial despite the uncertainty of its future, following the July summit with the FDA and outside advisors over the potential for cardiovascular risk.

In April GlaxoSmithKline reportedly added dozens of new international sites to the TIDE clinical trial. The TIDE trial is being conducted in Pakistan, India, Mexico, Latvia and Columbia, as well as in the US and other countries.

The dean of Wake Forest's medical school, William Applegate, told the Wall Street Journal that Wake Forest is "not succeeding in recruiting anybody," despite the fact that efforts to enlist patients began last year.

An oft-outspoken critic of Avandia, Dr. Sidney Wolfe of the consumer advocacy group Public Citizen, fears the potential for lack of informed consent if Avandia's safety concerns are not fully explained to study participants.

Avandia was approved for use in the US by the FDA in 1999 and was generating annual revenues of $3 billion by its seventh year on the market. That all changed when a report appeared in 2007 in the New England Journal of Medicine, linking Avandia to a 43 percent increased risk of heart attack.

In recent weeks GlaxoSmithKline agreed to a $60 million settlement stemming from 700 lawsuits alleging that Avandia caused heart attacks and other health problems. GlaxoSmithKline continues to face more than 4000 lawsuits over Avandia.