Results of a randomized phase III/IV trial comparing intermittent bolus versus continuous infusion of antihaemophilic factor (recombinant) in adults with severe or moderately severe haemophilia A undergoing major orthopaedic surgery

Abstract

Introduction In patients with haemophilia A undergoing surgery, factor VIII (FVIII) replacement therapy by continuous infusion (CI) may offer an alternative to bolus infusion (BI). Aim To compare the perioperative haemostatic efficacy and safety of antihaemophilic factor (recombinant) (ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) CI or BI administration. Methods In this multicentre, phase III/IV, controlled study (NCT00357656), 60 previously treated adult patients with severe or moderately severe disease undergoing elective unilateral major orthopaedic surgery (knee replacement, n = 48; hip surgery, n = 4; other, n = 8) requiring drain placement were randomized to receive antihaemophilic factor (recombinant) CI (n = 29) or BI (n = 31) through postoperative day 7. Primary outcome measure was cumulative packed red blood cell (PRBC)/blood volume in the drainage fluid within 24 h after surgery, used to establish non‐inferiority of CI to BI. Results CI:BI ratio of cumulative PRBC volume in the 24‐h drainage fluid was 0.92 (p‐value <.001 for non‐inferiority; 95% confidence interval, 0.82–1.05). Total antihaemophilic factor (recombinant) dose per kg body weight received in the combined trans‐ and postoperative periods was similar with CI and BI to maintain targeted FVIII levels during/after surgery. Treatment‐related adverse events (AEs) were reported in five patients treated by CI (eight events) and five treated by BI (six events), including two serious AEs in each arm. Conclusion CI administration of antihaemophilic factor (recombinant) is a viable alternative to BI in patients with haemophilia A undergoing major orthopaedic surgery, providing comparable efficacy and safety.

How do we optimally utilize factor concentrates in persons with hemophilia?

“…9 During the perioperative period, both stan dard half-life (SHL) and extended half-life (EHL) CFC can be given via con tin uous infu sion or inter mit tent bolus. [10][11][12] Prophylaxis as the stan dard of care Since com ple tion of the Joint Outcome Study, 13 and ESPRIT 14 study for children with severe HA, and the SPINART study 15 for adolescents and adults with severe HA, the use of pro phy laxis fac tor replace ment ther apy is now con sid ered the stan dard of care. The recently updated WFH guide lines rec om mend that pedi at ric and adult patients with hemo philia with a severe pheno type (to include those with mod er ate hemo philia with a severe phe no type) be on pro phy laxis to pre vent spon ta ne ous and break through bleed ing at all times.…”