rmacokinetic assessment performed before surgery. The median duration of treatment was 3.5 days (range: 1 to 17 days) for minor surgery and 9 days (range: 1 to 17 days) for major surgery.
In both studies, assessments of the hemostatic efficacy of Humate-P in preventing excessive bleeding were performed at the end of surgery, 24 hours after the last infusion of Humate-P, and at the end of the study (14 days following surgery).
Table 10 summarizes the end-of-surgery hemostatic efficacy assessments in subjects participating in either the US or European study.
Table 10: Investigator's End-of-Surgery Hemostatic Efficacy Assessments for the US and European Surgical Studies Number of Subjects End-of-Surgery Hemostatic Efficacy Assessments
Effective
(Excellent / Good)* 95% Confidence Interval (CI) for Effective Proportion†
*
Excellent: Hemostasis clinically not significantly different from normal.
Good: Mildly abnormal hemostasis in terms of quantity and/or quality (e.g., slight oozing).
†
95% CIs according to Blyth-Still-Casella.
‡
One subject with missing information.
US study 35 32 (91.4%) 78.5-97.6%
European study 26‡ 25 (96%) 82-99.8%
Table 11 summarizes the overall hemostatic efficacy assessments in subjects participating in either the US or European study. Humate-P was effective in preventing excessive bleeding during and after surgery.
Table 11: Investigator's Overall Hemostatic Efficacy Assessments for the US and European Surgical Studies Number of Subjects Overall Hemostatic Assessments
Effective
(Excellent / Good)* 95% CI for Effective Proportion†
*
Excellent: Hemostasis clinically not significantly different from normal.
Good: Mildly abnormal hemostasis in terms of quantity and/or quality (e.g., slight oozing).
†
95% CIs according to Blyth-Still-Casella.
‡
Overall hemostatic efficacy was assessed 24 hours after the last Humate-P infusion or 14 days after surgery, whichever came earlier.
§
Overall hemostatic efficacy was not prospectively defined for the European study; the efficacy result displayed is the least efficacious ranking assigned by an investigator between surgery and Day 14.
US study‡ 35 35 (100%) 91.3-100%
European study§ 27 26 (96.3%) 82.5-99.8%
In the US study, all efficacy assessments were reviewed by an independent Data Safety Monitoring Board (DSMB). The DSMB agreed with the investigators' assessments of the overall hemostatic efficacy for all but two subjects (neither of whom had type 3 VWD). Based on this, the DSMB judged hemostatic efficacy as "effective" in 33 (94.3%) (95% CI: 81.1% to 99.0%) of the 35 subjects.
In the US study, the median actual estimated blood loss did not exceed the median expected blood loss, regardless of the type of surgery. Table 12 shows the median expected and actual estimated blood loss during surgery in the US study.
Table 12: Expected and Actual Estimated Blood Loss During Surgery in the US Study Estimated Blood Loss Oral Surgery
(n=3) Minor Surgery
(n=4) Major Surgery
(n=28) Total
(n=35)
*
One subject with missing information
†
Five subjects with missing information
Expected – Median (range) mL 10 (5-50) 8 (0-15) 50 (0-300)* 20 (0-300)*
Actual – Median (range) mL 3 (0-15) 3 (0-10) 26 (0-300)† 18 (0-300)†
In the US s |
