Analysis of the Japanese subgroup in LEOPOLD II: a phase 2/3 study of BAY 81-8973, a new recombinant factor VIII product
International Journal of Hematology. 2016;105((3):):280-286
BAY 81-8973, a new full length recombinant FVIII product, has been developed for prophylaxis and on-demand therapy in patients with hemophilia A. LEOPOLD II was a phase 2/3 study comparing prophylaxis versus on-demand treatment with BAY 81-8973. The analysis herein evaluated the clinical profile in Japanese subjects enrolled in LEOPOLD II. The LEOPOLD II was an open-label randomized crossover study. Our analysis evaluated the efficacy using the annualized bleeding rate, safety, and pharmacokinetics in Japanese subjects with severe hemophilia A enrolled in LEOPOLD II. The median annualized bleeding rate was 59.9/year in the on-demand group and 1.9/year in the prophylaxis group for Japanese subjects. There were no study drug-related adverse events in the Japanese subjects. None of the subjects developed FVIII inhibitors. There were no apparent clinical differences in efficacy, safety, and pharmacokinetics between the Japanese and the non-Japanese subjects. Data for the Japanese subjects showed annualized bleeding rates to be remarkably lower in the prophylaxis group compared to the on-demand group and that BAY 81-8973 exhibited a good safety profile and tolerability. These results were similar for the non-Japanese subjects. The results support adoption of BAY 81-8973 for treatment of Japanese subjects with severe hemophilia A.
Does fibrin glue reduce lymph leakage (pleural effusion) after extended esophagectomy? Prospective randomized clinical trial
World Journal of Surgery. 2003;27((7):):776-81.
Fibrin glue has been shown to be effective in improving postoperative chylothorax following various thoracic procedures and in reducing lymphorrhea after axillary dissection. It is unknown, however, whether fibrin glue is effective in reducing lymph leakage (pleural effusion) after esophagectomy. A series of 43 consecutive patients with thoracic esophageal cancer who underwent extended esophagectomy were prospectively randomized to two groups: group A (n = 21), in whom 3 ml of fibrin glue was applied to the dissected mediastinum; and group B (n = 22), in whom fibrin glue was not applied. The time of drain removal and the volume of the thoracic drainage were compared. All data were expressed as the mean +/- standard deviation. There were no significant differences in the clinicopathologic characteristics between the two groups. None of the patients developed chylothorax or died during their hospital stay. The daily volume from the thoracic drain (457 +/- 273 ml) was significantly (p < 0. 05) larger on postoperative day (POD) 1 in group A than in group B (298 +/- 158 ml) and tended to be larger (p < 0. 10) on PODs 4 and 6 in group A than in group B. The cumulative drainage volume was significantly (p < 0. 05) larger on PODs 4 to 6 and POD 9, and it tended to be larger (p < 0. 10) on PODs 1, 3, 7, 8, 10, and 11 in group A than in group B, suggesting that the cumulative drainage volume in group A was consistently larger than that in group B. The cumulative numbers of patients with a drain remaining in place were not significantly different for the two groups (p = 0. 4683). Three patients in group A, however, had prolonged insertion (> 20 days) of the chest tube. There were no significant differences in the incidence of postoperative chest-related complications. No patients in group A developed viral infectious disease during the long-term follow-up. Application of fibrin glue to the dissected mediastinum seems to induce postoperative lymph leakage and thus be responsible for prolonged chest tube insertion in some patients. Hence the use of fibrin glue cannot be recommended for reducing lymph leakage after esophagectomy.
Application of cryoprecipitate as a hematostatic glue
Journal of Cardiovascular Surgery. 1998;39((5):):609-12.
BACKGROUND The effectiveness of cryoprecipitate, harvested from a patient's own fresh frozen plasma, for use in cardiac surgery as a hematostatic glue was studied in 32 randomized elective adult cardiac surgery patients from January 1993 to July 1994. MATERIALS AND METHODS Patients from the Toho Sakura Hospital were randomly allocated to two groups: Group 1 (n=11) received conventional fibrin glue presently available in our institution; while Group 2 (n=21) received autologous cryoprecipitate as a hematostatic glue. Surgical procedures broken down by group were as follows: Group 1: 4 CABG, 5 valvular surgeries and 2 other. Group 2: 11 CABG, 6 valvular surgery, 4 other. We preserved the patient's own blood and stored pure red cell and fresh frozen plasma (FFP). Cryoprecipitate was prepared from the FFP and preserved until required. RESULTS Cryoprecipitate had a 5-fold increase in fibrinogen activity (1190+/-311 mg/dl vs 238+/-34 mg/dl p<0.001), a 10-fold increase in factor VIII activity (362+/-219% vs 34+/-11%, p=0.001), and 4.5-fold increase in factor XIII activity (538+/-213% vs 119+/-50%, p<0.001), compared to serum. The amount of bleeding postoperatively was slightly lower in the cryoprecipitate glue group compared to the conventional glue group, but this was not significantly different. CONCLUSIONS We conclude that autologous samples of human cryoprecipitate prepared from a patient's own FFP had a strong hematostatic effect compared to conventional fibrin glue and was a very valuable hematostatic agent during cardiac surgery.