TY - JOUR
T1 - Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery
AU - Gill, Ravi
AU - Herbertson, Mike
AU - Vuylsteke, Alain
AU - Olsen, Peter Skov
AU - von Heymann, Christian
AU - Mythen, Monty
AU - Sellke, Frank
AU - Booth, Frank
AU - Schmidt, Thomas Andersen
N1 - Keywords: Adult; Aged; Aged, 80 and over; Blood Transfusion; Coronary Artery Bypass; Factor VIIa; Female; Humans; Male; Middle Aged; Placebos; Postoperative Hemorrhage; Recombinant Proteins; Reoperation; Treatment Outcome
PY - 2009
Y1 - 2009
N2 - BACKGROUND: Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed after cardiac surgery. METHODS AND RESULTS: In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients suffering critical serious adverse events. Secondary end points included rates of reoperation, amount of blood loss, and transfusion of allogeneic blood. There were more critical serious adverse events in the rFVIIa groups. These differences did not reach statistical significance (placebo, 7%; 40 microg/kg, 14%; P=0.25; 80 microg/kg, 12%; P=0.43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0.03) or required allogeneic transfusions (P=0.01). CONCLUSIONS: On the basis of this preliminary evidence, rFVIIa may be beneficial for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa.
AB - BACKGROUND: Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed after cardiac surgery. METHODS AND RESULTS: In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients suffering critical serious adverse events. Secondary end points included rates of reoperation, amount of blood loss, and transfusion of allogeneic blood. There were more critical serious adverse events in the rFVIIa groups. These differences did not reach statistical significance (placebo, 7%; 40 microg/kg, 14%; P=0.25; 80 microg/kg, 12%; P=0.43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0.03) or required allogeneic transfusions (P=0.01). CONCLUSIONS: On the basis of this preliminary evidence, rFVIIa may be beneficial for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa.
U2 - 10.1161/CIRCULATIONAHA.108.834275
DO - 10.1161/CIRCULATIONAHA.108.834275
M3 - Journal article
C2 - 19546387
SN - 0009-7322
VL - 120
SP - 21
EP - 27
JO - Circulation
JF - Circulation
IS - 1
ER -