A Canadian trial involving the antifibrinolytic drug Trasylol (aprotinin), used to control bleeding in high risk heart surgery patients has been halted. Trial patients on Trasylol (aprotinin), made by German-based drug company Bayer, appeared to be at a higher risk of death compared to patients treated with the other two antifibrinolytic drugs, aminocaproic acid and tranexamic acid. The patients were having a repeat bypass operation or having one or more valves replaced.
Antifibrinolytic drugs reduce excessive bleeding by inhibiting fibrinolysis, a process that breaks down blood clots.
Bayer said it immediately informed health authorities worldwide, including the US Food and Drug Administration (FDA), who have issued an “Early Communication About an Ongoing Safety Review of Aprotinin Injection”.
Bayer said they have not seen the data from the trial yet so are not in a position to do their own analysis or evaluation. The trial involves a number of centres throughout Canada and it will take up to 8 weeks to get the data together.
The trial was halted by the trial’s executive committee when it received a letter from the trial’s safety board stating that the results were starting to show Trasylol reduced bleeding but was also starting to show a significant link to increased risk of death from all causes compared to the other two drugs.
The trial is called BART, Blood Conservation using Antifibrinolytics: A Randomized Trial in High-Risk Cardiac Surgery Patients, and involves 3000 high risk cardiac patients having either a repeat operation for coronary heart bypass graft (CABG) or an operation to replace an aortic valve, or combined valves or valve/CABG procedures.
The drug company said it had issued new guidance to physicians and healthcare providers using Trasylol (aprotinin injection) to treat patients having coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) who were at increased risk of blood loss or blood transfusion.
Bayer recommends that physicians use Trasylol only as directed by the approved product label which says the drug 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 surgery who are at an increased risk for blood loss and blood transfusion.”
The drug company also recommends doctors take into account the fact the BART trial has been halted because of “an increase in all-cause mortality in patients in the aprotinin treatment arm compared to patients who received either aminocaproic acid or tranexamic acid”.
As the data from the BART trial becomes available, Bayer and health authorities such as the FDA will re-evaluate the overall risk-benefit of Trasylol and decide whether the label and/or product information needs to be changed.
There are a number of important safety considerations with the use of Trasylol, including a risk of fatal anaphylactic or anaphylactoid reactions, which is higher in patients who have had aprotinin before. Bayer also said that the drug should only be given in instances where “cardio-pulmonary bypass can be rapidly initiated”. And the benefits of the drug should be balanced against the risk of anaphylaxis linked to any subsequent exposure to aprotinin.
There are a number of other safety considerations that are listed on both the drug company and the FDA websites.
Click here for information on Trasylol from the product manufacturer (Bayer).
Click here to search Drugs@FDA for FDA label information (enter Trasylol in the search box).
Written by: Catharine Paddock