A 10-year, randomized, clinical trial on prophylaxis vs. on-demand treatment in children with haemophilia A : the E.S.P.R.I.T. study

Introduction: Primary prophylaxis has been showed to lower the bleeding frequency and progressive joint damage. The Italian ESPRIT (Evaluation Study on Prophylaxis: a Randomized Italian Trial) was designed to evaluate efficacy and safety of prophylaxis compared to on-demand treatment (ODT) over a 10-year follow-up period. Methods: Forty children with severe hemophilia A (FVIII <1%) (CWH), aged ≤ 7 years (median 2 years), with negative clinical-radiological joint score at entry and at least 1 bleed during the previous 6 months were randomized to receive prophylactically Recombinate?25 U Kg-13 times a week or on-demand treatment with ‡25 U Kg-1until complete healing. Safety, feasibility, efficacy in preventing bleeding episodes and arthropathy, direct costs and quality of life were evaluated on an intent-to-treat basis. Results: Ten of 21 prophylaxis children required indwelling catheters, while none of 19 ODT children did. Three patients on prophylaxis and 2 ODT patients developed inhibitors. Prophylaxis with ≤ 25 IU Kg-1maintained FVIII >1% in 7 of 18 prophylaxis patients (39%) without inhibitors. Prophylaxis children showed a significant lower number of breakthrough bleeds compared to ODT children (0. 52 vs. 1.08 bleeds/patient/month respectively. P < 0.05), with 0.20 joint bleeds/month vs. 0.52 in ODT children (P < 0.02). Radiological evaluation showed signs of haemophilic arthropathy in 6 prophylaxis patients (29%) (median Petterson score 5; range: 3–14) and in 14 ODT patients (74%) (median score 8; range: 2–12) (P < 0.05). Prophylaxis was more effective when started at younger ages ( ≤ 36 months). Conclusions: This study confirms safety, feasibility and efficacy of prophylaxis in preventing bleeds and arthropathy in CWH