Drug News
Bayer Trasylol trial halted due to high risk of death
By Sue Mueller
Oct 26, 2007 - 10:30:42 AM

FRIDAY October 26, 200& (Foodconsumer.org) -- Use of Trasylol also known as aprotinin may significantly increase risk of death in patients at an increased risk of blood loss and blood transfusion because of coronary artery bypass graft surgery with cardiopulmonary bypass, the Food and Drug Administration reported October 26.

The finding was derived from a trial titled Blood conservation using antifibrinolytics: A randomized trial in a cardiac surgery population (BART) study that planned to enroll approximately 3,000 adult Canadian patients who were to undergo various types of cardiac surgery that placed them at high risk for bleeding. As a result, the study was terminated earlier than planned.

Aprotinin is indicated for prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft (CABG) surgery who are at an increased risk for blood loss and blood transfusion.  

The study was meant to determine if aprotinin is superior to other antifibrinolytic drugs such as epsilon-aminocaproic acid or tranexamic acid.  It turned out that aprotinin imposed a higher risk of death compared to its two competitors.

The BART Executive Committee notified the FDA and the drug manufacturer of the increased death risk and its decision to discontinue the study on Trasylol.

According to the FDA, the findings resulting from the aborted study include:

The 30- day mortality in the aprotinin group nearly had reached conventional statistical significance at the interim analysis, when compared to either epsilon-aminocaproic acid or tranexamic acid;

A trend toward increased mortality in the aprotinin group had been observed throughout the study;

The use of aprotinin was associated with less serious bleeding than either of the comparator drugs; however, more deaths due to hemorrhage had been observed among patients receiving aprotinin;

Bayer Pharmaceuticals Corp., Leverkusen, Germany, the manufacturer of Trasylol, on October 26 issued additional guidance to physicians after the company was notified that use of aprotinin was linked to increased risk of mortality in high risk cardiac surgery patients.

Bayer said in its Guidance that physicians should use Trasylol in accordance with approved product labeling.   Also they should consider the fact that the BART Trial has been discontinued due to increased all-cause mortality in patients who were treated with the drug compared to those who were treated with either aminocaproic acid or tranexamic acid.

The drug of concern was approved in 1993. And it’s been more than a year that the increased risk of death, serious kidney damage and stroke became public, according to Reuters. In 2006, the FDA revised the labeling for Trasylol to address the risk and limit its approved usage to patients at an increased risk for blood loss and blood transfusion during coronary bypass graft surgery.

On October 26, the FDA issued Early Communication about an Ongoing Safety Review of Aprotinin Injection saying that the federal agency was notified of the halted study due to the unexpectedly higher risk of death.  It said "FDA anticipates further review of the risk and benefits of Trasylol, which may result in additional labeling or other regulatory action. FDA will work with the sponsor of the recently terminated study to evaluate the data fully."

In the meantime, the FDA recommends that physicians weigh the risks and benefits of Trasylol outlined in the label and in the Early Communication about an Ongoing Safety Review, and discuss the information with their patients.