This target population size will provide 80% power to detect a statistically significant (P < 0.05) difference in inhibitor rate between the rFVIII and pdVWF/FVIII groups. SIPPET has several important secondary VX-809 supplier objectives

in relation to the natural histories of haemophilia and inhibitor development. Thus, ancillary studies will provide a significant period of prospective follow-up, in a ‘real-world’ setting, regarding influence on inhibitor rate of the following parameters: age at first bleed; bleeding pattern (site, frequency); and possible issues associated with bleeding pattern or the early or late occurrence of bleeding (e.g. factor II or V mutations, or other ‘gain-of-effect’ polymorphisms). Regarding inhibitor development, major secondary objectives include assessments of the modality of inhibitor occurrence, based on issues such as the number of EDs, inhibitor titres at treatment onset and anamnestic responses. The frequency of transient inhibitors will also be evaluated, as will clinical and laboratory issues with a possible influence on inhibitor development (Table 4), irrespective of the type of concentrate used. Overall, 87 centres are involved in the SIPPET study (Table 5). Almost 60% of centres (n = 50) have proceeded through regulatory

stages, have gained ethics committee this website approval and are about to start, or are already, actively the recruiting patients. Most of the active centres are situated in Europe (n = 22), the United States (12) and Asia (10). To date, a total of 159 patients have been enrolled over a 20-month period (Fig. 4). Most of these patients are living in India (n = 85), Egypt (44) and the United States (10). Among the enrolees, mean age at first bleed was 9.4 months, mean age at diagnosis of haemophilia was 11.2 months, and mean age at enrolment was 22.8 months. A total of 64 enrolees had 128 bleeds before enrolment. These bleeds were managed primarily with fresh frozen plasma (36%

of cases) and cryoprecipitate (46%) administered for <5 EDs; this issue will be taken into account during final analysis of the study findings. Altogether, 147 patients have now been randomized to treatment: that is, 11 patients failed screening because of FVIII levels ≥1%. Among the 147 randomized patients, 11 have withdrawn from the trial, 23 have not been treated, because they have not yet had a bleed and have not yet received concentrate, and 113 have had ≥1 ED to study treatment. In the group of 113 treated patients, 13 (11.5%) have developed inhibitors. Importantly, an interim analysis will be performed, to confirm that the study is meeting its goals, when 150 patients have been enrolled and treated for ≥20 EDs. Although debatable, it is thought that approximately one-third of boys with severe haemophilia A will develop an inhibitor.