Mechanism Of Action
Octaplas replaces human plasma proteins.
Coagulation factor activities in the final product are controlled to obtain levels within the range of normal human plasma. Protein S and alpha2-antiplasmin, which are labile to S/D treatment, are controlled to ensure levels in the final product of ≥ 0.4 International Units (IU) per mL.
The Octaplas predecessor product was studied in liver disease, liver transplantation, cardiac surgery and TTP.
An open-label parallel group study was performed in surgical patients who were allocated to receive either a single infusion of Octaplas (n=20) or no plasma treatment (n=26) during open-heart surgery.10 A historical control group of patients having received standard single-donor FFP (n=20) was used to compare the efficacy and safety. The average dose of Octaplas was 700 mL (range 200 to 3400 mL), compared with 1012 mL (range 500 to 4000 mL) for standard FFP. The choice of plasma product (Octaplas or FFP) did not appear to influence the postoperative course with respect to volume of postoperative bleeding, the need for reoperation secondary to bleeding, or the length of the postoperative hospital stay. This study was not powered to detect any difference in efficacy.
A prospective, single-blind, randomized study was designed to investigate the safety and efficacy of Octaplas compared with standard FFP in adult patients with coagulopathies due to liver disease (LD) or liver transplantation (LTX), or for the management of newly diagnosed thrombotic thrombocytopenic purpura (TTP).11 -13 In total, 55 patients were included in the study. Three patients were suffering from TTP and all received Octaplas. Of the 24 patients with LD, 11 were treated with Octaplas, and out of the 28 LTX patients, 13 received Octaplas. Within the LD and the LTX groups, patients were comparable in all clinical aspects and in the dose of plasma given. There were no relevant changes in any of the coagulation factors, but protein C and fibrinogen improved considerably in both groups, accompanied by a corresponding improvement in partial thromboplastin time (PTT) levels 24 hours after infusion. Similar degrees of correction of prolonged international normalized ratio (INR) and PTT values were achieved with both Octaplas and FFP. All 3 patients with TTP attained platelet counts of >50x109/L by Day 10. This study was not powered to detect any difference in efficacy.
A prospective, non-randomized open-label study in intensive care patients was conducted in post-operative open heart surgery patients in the surgical intensive care unit who were in need of plasma transfusion for acute bleeding or for the risk of bleeding.14 There were a total of 67 patients, 36 who received Octaplas (600 mL) and 31 who received FFP (600 mL). Parameters measured included PT, PTT, free Protein S and plasmin inhibitor. Parameters were measured before treatment and 60 minutes after termination of plasma infusion. The decrease in PT and PTT, and the rise in free Protein S were similar between the two study arms. Plasmin inhibitor declined after Octaplas and remained unaffected by FFP. Clinical hemostasis evaluations were also similar between the two treatment regimens. This study was not powered to detect any difference in efficacy.
In a randomized, open-label, controlled study, 60 healthy adult volunteers (mean age 32.6±9.1 years) received after a standard plasmapheresis (PPh) of 600 mL plasma, an administration of 1200 mL of Octaplas or the predecessor product in a cross-over design. Coagulation factors (FI, FII, FV, FVII, FVIII, FIX, FX, and FXI) and hemostatic parameters (aPTT, PT and protein C) were assessed post-infusion at 15 minutes, 2 hours and 24 hours. The primary analysis was to demonstrate equivalence for recoveries using a 10% margin. All coagulation and hemostatic parameters met the equivalence criterion. To verify the assumption of improvement of plasmin inhibitor (PI) concentrations, a test for superiority was conducted. Statistically significant differences between treatments were found at 15 minutes (P=0.0012) and 2 hours (P=0.0190) post-transfusion for the per protocol population. Increased levels of PI post-infusion of Octaplas, as compared to the predecessor product may be attributable to the increased concentrations of PI.
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