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

INTERVENTION: Trade Name: Minrin Pharmaceutical Form: Solution for injection/infusion Trade Name: Octostim Pharmaceutical Form: Solution for injection CONDITION: Hemophilia A ; MedDRA version: 19.0 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) System Organ Class: 100000004850 ; MedDRA version: 19.0 Level: LLT Classification code 10053753 Term: Hemophilia A without inhibitors System Organ Class: 100000004850 ; MedDRA version: 19.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850 Therapeutic area: Diseases [C] ‐ Blood and lymphatic diseases [C15] SECONDARY OUTCOME: Secondary end point(s): a) Number and nature of bleeding during the first 14 days after the minor intervention (appendix VI); a) Other adverse events during the first 14 days after the minor intervention; b) Treatment costs in both treatment arms; c) The proportion of patients with FVIII plasma levels within set target levels after the minor intervention; d) Experienced quality of care in participating patients; e) Discrepancies between one‐stage and chromogenic FVIII‐measurements before and after desmopressin administration; f) Inhibitor development 4‐6 weeks after the minor intervention; Timepoint(s) of evaluation of this end point: Every endpoint will be evaluated at the end of study INCLUSION CRITERIA: In order to be eligible for this study, a subject must meet all of the following criteria: ‐ Non‐severe hemophilia A patients (FVIII 0.01‐0.40 IU/mL) ‐ In need of a minor surgical intervention ‐ Age minimally 12 and maximally 70 years at study inclusion date ‐ Need for perioperative FVIII concentrates for a maximum of 48 hours ‐ Having admissible results of a desmopressin test (see paragraph 3.1) ‐ Absolute increase in FVIII 1 hour after desmopressin administration = 0.2 IU/mL after a previous (test) dose ‐ Male gender ‐ (Parental) informed consent Are the trial subjects under 18? yes Number of subjects for this age range: 7 F.1.2 Adults (18‐64 years) no F.1.2.1 Number of subjects for this age range 61 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7 PRIMARY OUTCOME: Main Objective: Primary Objectives: ; 1) To show the efficacy of desmopressin and FVIII concentrate combination treatment is equal to the efficacy of FVIII monotherapy; 2) To show a reduction in FVIII concentrate consumption with desmopressin and FVIII concentrate combination treatment compared to FVIII monotherapy; Primary end point(s): To assess our first main objective, efficacy of treatment is measured. Efficacy is defined as the average deviation of FVIII peak level to the predicted FVIII peak range in IU/mL in each treatment arm, without administering FVIII concentrate outside the dosing advice. The FVIII level for the primary endpoint is measured prior to the minor intervention, 10‐15 minutes after the infusion of FVIII concentrate. The measurement for the primary endpoint is marked in appendix VIII. The deviation will be set to 0 for every FVIII measurement that falls into the predicted FVIII range. The predicted FVIII range will be set to the predicted peak level +/‐ 10%. Example: ; A patient has a target target trough FVIII value of 0.5 IU/mL after 24 hours. In order to keep the FVIII level above 0.5 IU/mL for the first 24 hours after the minor intervention, it is predicted the FVIII peak level will be as high as 1.10 IU/mL. The target range will then be set to 0.99‐1.21 IU/mL. ; Predicted FVIII levels will never be lower than the FVIII target levels as described in paragraph 3.3 and 3.7.; The FVIII concentrate consumption, our second main objective, will be evaluated as units per kilogram. Therefore, all units of administered FVIII concentrate and the body weight of each patient will be documented. The consumption of FVIII concentrate in units per kilogram will be calculated.; Secondary Objective: Secondary Objectives: ; a) To evaluate the safety of both treatment arms, i.e. occurrence of bleeding, dosing below target and other adverse events.; b) To perform an economical evaluation to quantify the costs of combination treatment compared to standard treatment.; c) To compare the proportion of patients with FVIII plasma levels within set target levels after the minor intervention.; d) To evaluate experienced quality of care in participating patients.; e) To evaluate discrepancies between one‐stage and chromogenic FVIII‐measurements before and after treatment with desmopressin.; f) To evaluate the occurrence of FVIII inhibitors.; Timepoint(s) of evaluation of this end point: Both endpoints will be evaluated at the end of study.