Bayer stops Canadian-led drug trial over concerns of increased death rates

-Canadian Press

10/26/2007 - Drug giant Bayer Inc. confirmed Thursday that a large Canadian-led trial studying its drug Trasylol (aprotinin) has been halted because of concerns the drug increased the risk of death among people who received it.

The U.S. Food and Drug Administration also posted a statement on the observed risk from the study, known as the BART trial, saying the agency will consider the new evidence as part of its ongoing deliberations on whether the drug should be removed from the market or have additional warnings on its label.

The drug is used to prevent massive bleeding during coronary bypass surgery.

"In light of the preliminary BART study findings, FDA anticipates re-evaluation of the overall risks and benefits of Trasylol," the U.S. drug regulator said.

"This re-evaluation may result in the need to revise the labelling or other regulatory actions. Until this process has been completed, health-care providers who are considering use of Trasylol should be aware of the risks and benefits described in the labelling for Trasylol and the accumulating data suggesting Trasylol administration increases the risk for death compared to other antifibrinolytic drugs."

Bayer also issued new guidance to doctors, telling them they should only use Trasylol as directed on the drug's label while records of the multi-centre, multi-year trial are reviewed.

"Bayer will continue to work closely with medical experts, the FDA and health authorities in countries where Trasylol is marketed to re-evaluate the overall risk-benefit of the product and will evaluate the need for a label change and-or other actions as additional data and analyses become available from the BART trial," the company said in a statement.

The BART trial was testing the drug against two other medications in the same class.

The principal investigator of the trial is Dr. Paul Hebert, a researcher at the Ottawa Health Research Institute. Hebert is also editor of the Canadian Medical Association Journal.

Hebert did not immediately respond to requests for an interview.

The study's full name is actually "Blood Conservation using Antifibrinolytics: A Randomized Trial in High-Risk Cardiac Surgery Patients," but it goes by the acronym BART.

It is a multi-centre randomized controlled trial to compare the efficacy and safety of aprotinin, aminocaproic acid and tranexamic acid.

Approximately 3,000 high-risk cardiac surgical patients undergoing either re-operation for coronary heart bypass graft or aortic valve replacement, or combined valves or valve-graft procedures were to be randomly assigned to one of the drugs.

When a periodic analysis of data from the trial showed increased deaths among the aprotinin group, the trial's executive board decided to cut off enrolment in the study and informed drug regulators and the company.

The FDA had already been studying the drug, which has been linked to fatal cases of anaphylactic shock, kidney failure, heart attack and stroke.

An expert panel convened by the U.S. drug regulator voted in mid-September to recommend that Trasylol stay on the market.

The FDA's statement Thursday said it hadn't yet concluded whether the new information requires it to take regulatory action against the drug.

Trasylol is licensed in 69 countries, said Bayer spokeswoman Staci Gouveia, noting that in the company's global database of randomized trials involving more than 4,400 patients, there was no statistically significant difference in death between patients treated with the drug and those given a placebo.

In an e-mail interview, Gouveia said 2.9 per cent of patients treated with full-dose aprotinin and 2.5 per cent of those on placebo "died in the perioperative period."

Adverse events - including anaphylaxis, kidney failure, stroke and heart attack - are routinely reported to the FDA and are described in the product prescribing information, she said.

Ennis & Ennis, P.A. is representing individuals that have been harmed as a result of Trasylol side effects. If you or a loved one have suffered as a result of Trasylol side effects such as kidney failure, heart attack, or stroke you may be entitled to compensation. For more information about a Trasylol lawsuit, a possible Trasylol recall, or for questions regarding Trasylol class action lawsuits click here for a free, confidential case evaluation.