Information about the Blood Conservation using Antifibrinolytics in a Randomized Trial (BART) Study
October 25, 2007
Following advice from an independent Data Safety Monitoring Board, a major clinical trial in cardiac surgery was stopped by the lead researchers.
The BART (Blood Conservation using Antifibrinolytics in a Randomized Trial) study was designed to compare three antifibrinolytic drugs routinely used in clinical practice in 2,970 high-risk cardiac surgery patients. The study was centrally administered by the Ottawa Hospital Research Institute, with patients enrolled at 19 centres across Canada.
The three drugs examined, aminocaproic acid, aprotinin and tranexamic acid, were all approved by Health Canada and were not considered investigational. No placebo group was included in the study because antifibrinolytic therapy is considered a standard of care in high-risk cardiac surgery patients. As the first large study to rigorously compare these three drugs in high-risk cardiac surgery patients, the BART study was expected to provide highly valuable evidence to clinicians and patients.
The BART study protocol was developed by independent, academic investigators in 1999-2000. It was evaluated by the peer-review process and in 2001 it received funding from the Canadian Institutes of Health Research and the Ontario Ministry of Health and Long-Term Care. There was no funding from the pharmaceutical industry for this trial and none of the three drug manufacturers had any role in its design, conduct or evaluation.
BART enrollment began in 2002, with patients assigned randomly to receive one of the three drugs. The study was double-blinded, so that neither the patients nor the investigators knew which drug was being administered. The primary outcomes to be analyzed included massive postoperative bleeding, massive transfusion, death due to hemorrhage, and the need for another operation due to hemorrhage. The BART study was evaluated and approved by Research Ethics Boards at 19 centres in Canada.
After reviewing preliminary data on 2,163 patients, the BART Data Safety Monitoring Board, which closely monitored the study throughout, found a trend towards an increase in all-cause 30-day mortality in the aprotinin arm of the study that almost reached conventional statistical significance. If confirmed in the final analysis, this trend would translate into approximately two additional deaths per one hundred patients receiving aprotinin.
On October 25, the US Food and Drug Administration issued a public communication regarding the preliminary results of the BART trial. It is available here: http://www.fda.gov/cder/drug/early_comm/aprotinin.htm. Patients are encouraged to discuss any concerns with their surgeon or anesthetist.
“It is important to stress that the results of the BART study analyzed to date are preliminary and although differences in mortality were detected, this result could change when the remaining data is added to the analysis,” said Dr. Dean Fergusson, Co-Chair of the BART study and a Senior Scientist at the Ottawa Hospital Research Institute.
“Aprotinin is a commonly administered antifibrinolytic drug, so this research has important implications for doctors and their patients," said Dr. Paul Hébert, BART Co-Chair and Senior Scientist at the Ottawa Hospital Research Institute. “We’re hopeful that the safety information emerging from the study will help improve the outlook for the many individuals who require bypass surgery and need antifibrinolytics to prevent serious bleeding.”
Director, Communications and Public Relations
Ottawa Hospital Research Institute
Phone: 613-798-5555 x 19691