Desmopressin and FVIII concentrate combination treatment in non-severe hemophilia A patients undergoing minor interventions

Rationale: Hemophilia A (HA) is a rare bleeding disorder, caused by factor VIII deficiency. In non-severe HA patients (FVIII 0.01-0.40 IU/mL), minor interventions, such as dental surgery and endoscopies, are an important treatment indication. Two treatment options are currently available: FVIII concentrate and desmopressin. Unfortunately, perioperative treatment is not optimal, as high bleeding rates after dental surgery, the most frequent occurring type of minor interventions, of 12% and 25% were found in two recent studies. Moreover, a previous evaluation of FVIII concentrate treatment from our centre shows a high rate of dosing above FVIII target levels (79%) and a rate of dosing below FVIII target levels of 8%. Both may lead to complications. Moreover, FVIII concentrate is expensive. Pharmacokinetic (PK) guided dosing, a patient tailored dosing method, can improve dosing accuracy.

Desmopressin, the second treatment option, releases endogenous FVIII and von Willebrand factor, improving hemostasis. Desmopressin is not ideal due to several barriers. Amongst others, most patients do not reach sufficient FVIII levels to undergo minor interventions. An increase in the use of desmopressin instead of FVIII concentrate would be highly beneficial, as desmopressin is cheaper and more widely available. Desmopressin and FVIII concentrate combination treatment may be an innovative treatment option.

Objective: To show the efficacy of combination treatment with desmopressin and FVIII concentrate is equal to the efficacy of FVIII concentrate monotherapy, but will reduce the FVIII concentrate consumption in non-severe hemophilia A patients around minor interventions.

Study design: Randomized controlled trial

Study population: Seventy non-severe hemophilia A patients (FVIII ¡Ý0.01 IU/mL), between 12-70 years of age, undergoing a minor intervention and requiring perioperative FVIII replacement therapy for a maximum of 48 hours.

Intervention (if applicable): The first group receives standard treatment consisting of FVIII concentrate monotherapy. The intervention group receives desmopressin and FVIII concentrate combination treatment.

Main study parameters/endpoints: The average deviation of the measured FVIII peak level to the predicted peak FVIII range before the minor intervention in IU per mL and the FVIII concentrate consumption in IU per kilogram.

Desmopressin and FVIII concentrate combination treatment will be equally effective as FVIII concentrate monotherapy, but will decrease the needed amount of FVIII concentrate significantly

preoperatively

14 days postoperatively

4-6 weeks postpoperatively

Desmopressin and FVIII concentrate combination treatment.