A randomized clinical trial on prophylaxis vs. episodic treatment in children with haemophilia A : the ESPRIT study

Introduction: Prophylaxis of bleeding events by regular replacement therapy has been shown to lower bleeding frequency and progressive joint damage. The Italian ESPRIT (Evaluation Study on Prophylaxis: a Randomized Italian Trial) study was designed to evaluate efficacy and safety of prophylaxis compared to episodic treatment over a 10-year follow-up period. Methods: Forty children with severe hemophilia A (FVIII < 1%), 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 Recombinate?25 U/Kg prophylactically three times a week or episodic treatment with ‡25 U/Kg until 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 children on prophylaxis required indwelling catheters, while none of 19 children on episodic treatment did. Three patients on prophylaxis and 2 patients on episodic treatment developed inhibitors. Prophylaxis with £ 25 IU/Kg maintained FVIII >1% in 7 of 18 prophylaxis patients (39%) without inhibitors. Prophylaxis children showed a significant lower number of breakthrough bleeds compared to children on episodic treatment (0.52 vs. 1.08 bleeds/patient/month respectively, P < 0.05), with 0.20 joint bleeds/month vs. 0.52 in children on episodic treatment (P < 0.02). Radiological evaluation showed signs of haemophilic arthropathy in six prophylaxis patients (29%) (median Petterson score 5; range: 3–14) and in 14 patients on episodic treatment (74%) (median score 8; range: 2–12) (P < 0.05). Prophylaxis was more effective when started at lower ages ( £ 36 months). Conclusions: This study confirms safety, feasibility, and efficacy of prophylaxis in preventing bleeds and arthropathy in children with haemophilia