Safety and efficacy of turoctocog alfa (NovoEight®) during surgery in patients with haemophilia A: results from the multinational guardian™ clinical trials

E Santagostino, S R Lentz, M Misgav, B Brand, P Chowdary, A Savic, Y Kilinc, Y Amit, A Amendola, L P Solimeno, T Saugstrup, I Matytsina, E Santagostino, S R Lentz, M Misgav, B Brand, P Chowdary, A Savic, Y Kilinc, Y Amit, A Amendola, L P Solimeno, T Saugstrup, I Matytsina

Abstract

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prevention and treatment of bleeding episodes in patients with haemophilia A. The present investigations from the multinational, open-label guardian(™) clinical trials assessed the haemostatic response of turoctocog alfa (NovoEight(®)), a rFVIII product, in patients with severe haemophilia A (FVIII ≤ 1%) undergoing surgery. All patients had a minimum of 50 exposure days to any FVIII product prior to surgery and no history of inhibitors. A total of 41 procedures (13 orthopaedic, 19 dental and 9 general) were performed in 33 patients aged 4-59 years. Of the 41 procedures, 15 were major surgeries in 13 patients and 26 were minor surgeries in 21 patients. The success rate for haemostatic response was 100% (success was defined as 'excellent' or 'good' haemostatic outcome). Turoctocog alfa consumption on the day of surgery ranged from 27 to 153 IU kg(-1). The mean daily dose declined over time, while retaining adequate FVIII coverage as measured by trough levels. Overall, no safety issues were identified. No thrombotic events were observed and none of the patients developed FVIII inhibitors. In conclusion, the present results show that turoctocog alfa was effective in controlling blood loss by obtaining a sufficient haemostatic response in patients with severe haemophilia A undergoing surgery.

Keywords: NovoEight®; clinical trial; haemophilia A; recombinant factor VIII; surgery; turoctocog alfa.

© 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Figures

Fig. 1
Fig. 1
Duration of surgery-related treatment and mean daily doses of turoctocog alfa (major surgeries, N = 13). For the mean daily doses, the number of patients at each time point corresponds to number of patients who were still in surgery-related treatment at that time point. Data points show mean dose (IU kg−1) and error bars represent ± standard error of the mean.
Fig. 2
Fig. 2
Trough levels during the first 7 days after surgery in patients undergoing major surgery. Data points show mean FVIII trough levels (IU mL−1) and error bars represent ± standard error of the mean. N represents number of surgeries.
Fig. 3
Fig. 3
Summary data of haemostatic outcome from major and minor surgeries.

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