Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: a randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy

Abstract

We investigated the effectiveness of prophylactic administration of recombinant activated factor VII (rFVIIa) for cardiopulmonary bypass surgery in children under 1 year old with congenital heart disease (CHD) in a double-blinded, placebo-controlled study. The rFVIIa dose was 40 microg/kg and all patients also received standard haemostatic replacement therapy. The primary endpoint was the time to chest closure from neutralization of heparin with protamine sulphate as this could be most objectively and accurately measured during surgery. Secondary endpoints were volumes of transfused blood, platelet concentrates and fresh-frozen plasma. All adverse events were recorded. In the intention-to-treat analysis there were 76 patients (40 in rFVIIa group and 36 in placebo group). The demographics and severity of CHD were similar in both groups. No benefit of rFVIIa prophylaxis was found in the time to chest closure, which was significantly prolonged in the rFVIIa group (rFVIIa mean +/- SE, 98.8 +/- 27.27 versus 55.3 +/- 29.15, P = 0.0263). In the 41 patients available for a follow-up visit 6 weeks after discharge, the chest closure time was also prolonged in the rFVIIa group (P = 0.0515). There were no significant differences in the secondary endpoints. Adverse events were similar in both groups.

The role of recombinant factor VIIa in on-pump cardiac surgery: Proceedings of the Canadian Consensus Conference

“…Both cardiac surgery RCTs were small, preliminary studies. In the double-blinded study by Ekert et al, 14 rFVIIa or placebo were administered to 76 infants (< one year old) soon after termination of CPB and reversal of heparin. There were no differences in any of the efficacy outcomes, including time to sternal closure, blood loss, or amount of blood products transfused.…”

“…22 Another limitation of the study is that blood product transfusions were delayed for at least 30 min from rFVIIa administration. Since children are particularly susceptible to CPB-related dilutional coagulopathy, 14 this delay may have prevented rFVIIa from generating adequate amounts of thrombin to restore hemostasis during its short circulating half-life.…”

Use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without hemophilia: a systematic review and meta-analysis

“…28 Dosing regimens varied from a single dose of 5 µg/kg to multiple doses totalling 360 µg/kg. 22,26 The primary outcomes were predominantly blood loss, 25−27 red blood cell transfusion 16,[21][22][23]27,28 and number of patients receiving allogeneic transfusion. 15,20,21 Protocols for transfusion were reported in 8 of 11 RCTs.…”

“…This finding is likely to be an overestimate of the effect of recombinant factor VIIa, since four studies reporting no difference could not be incorporated into the pooled analysis because outcomes were not available as means and standard deviations. 16,21,23,25 Also, there was important statistical heterogeneity (I 2 = 78%); when we excluded studies with fewer than 50 patients, the I 2 value was 0%. Ten studies provided data on the use of red blood cell transfusion.…”

Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting

“…17 Seventy-six infants younger than age 1 were randomized between 40 g/kg of rFVIIa versus placebo. This age group was selected based on their susceptibility to dilutional coagulopathy and belief that rFVIIa therapy would avoid the need for treatment with other coagulation factors.…”