A double-blind, randomized, controlled study to explore the efficacy of rFVIIa on intraoperative blood loss and mortality in patients with severe acute pancreatitis
Thrombosis Research. 2014;133((4):):574-8.
BACKGROUND Severe acute pancreatitis is a life-threatening disease. Patients with peripancreatic necrotic infection often require surgical removal of necrotic infected tissue and a wide debridement will cause blood loss and worsen the condition. AIM: To assess whether treatment with NovoSeven, a recombinant activated FVII (rFVIIa), could improve coagulation function and therefore reduce blood loss, blood transfusion and all-cause mortality during necrosectomy in patients with infected necrosis secondary to severe acute pancreatitis. MATERIALS AND METHODS Severe acute pancreatitis patients admitted to Nanjing Jinling Hospital for necrosectomy were enrolled and randomized to receive either standard treatment or standard treatment plus an intravenous infusion of rFVIIa (40mug per kilogram of body weight per hour) before operation. The prospectively defined primary end points were perioperative coagulation parameters (prothrombin time, activated partial thromboplastin time), blood transfusion unit and blood loss. The secondary end points were operation time, ICU stay and all-cause mortality at 28days after the operation. RESULTS A total of 64 patients were enrolled (31 in the rFVIIa group and 33 in the control group). Treatment with rFVIIa was associated with a reduction in operation time, red blood cell and fresh froze plasma transfusion, blood loss and prothrombin time compared to the control group (p<0.05 for all). Activated partial thromboplastin time and mortality were similar between the two groups (P>0.05). CONCLUSION Treatment with rFVIIa significantly improved the extrinsic coagulation function in patients with severe acute pancreatitis and was associated with decreased risk of bleeding. However, rFVIIa did not improve intrinsic coagulation or reduce over-cause mortality. Clinical Trial Registration Number: ChiCTR-TRC-1300389. Copyright 2014 Elsevier Ltd. All rights reserved.
Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: an individual patient based meta-analysis of two controlled trials
Journal of Hepatology. 2014;61((2)):252-9.
BACKGROUND & AIMS Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data with special focus on high risk patients. METHODS The primary outcome measure was the effect of rFVIIa on a composite five day endpoint: failure to control bleeding, 5-day rebleeding or death. Analysis was based on intention to treat. High risk was defined as active bleeding on endoscopy while under vasoactive drug infusion and Child-Pugh score >8. RESULTS 497 patients were eligible for the meta-analysis; 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score >8. Analysis on the composite endpoint in all patients with bleeding from oesophageal varices did not show any beneficial treatment effect. However, failure rate for the primary composite end-point was significantly lower in treated patients with active bleeding at endoscopy (17%) compared to placebo (26%, p=0.049). This difference was highly significant in patients with Child-Pugh score >8 and active bleeding at endoscopy (rFVIIa 16%, placebo 27%; p=0.023). No significant treatment effect was found at 42 days. Five thromboembolic events occurred in rFVIIa treated patients compared to none in placebo treated patients. CONCLUSIONS The current meta-analysis shows a beneficial effect of rFVIIa on the primary composite endpoint of control of acute bleeding, prevention of rebleeding day 1-5 and 5-day mortality in patients with advanced cirrhosis and active bleeding from oesophageal varices at endoscopy. A major drawback of the treatment is a potential increased risk of arterial thrombo-embolic events. This treatment might be considered in patients with lack of control of bleeding after standard treatment.Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. RN 0 (Recombinant Proteins). 0 (recombinant FVIIa). EC 3-4-21-21 (Factor VIIa).
Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial
Hepatology (Baltimore, Md.). 2008;47((5):):1604-14.
A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P = 0. 37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 microg/kg rFVIIa compared with placebo (odds ratio 0. 31, 95% confidence interval = 0. 13-0. 74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 microg/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups. CONCLUSION Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups.
Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial
American Journal of Surgery. 2006;191((2):):245-9.
BACKGROUND Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy. METHODS Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events. RESULTS No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups. CONCLUSIONS Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.
Safety and efficacy of recombinant factor VIIa in patients with liver disease undergoing laparoscopic liver biopsy
BACKGROUND & AIMS Activated recombinant factor VII (rFVIIa) has been shown to be effective in correcting prolonged prothrombin time (PT) in cirrhotic patients. The main objective of this study was to evaluate the effect of 4 (5, 20, 80, and 120 microg/kg) doses of rFVIIa on correction of PT and the time to achieve hemostasis in cirrhotic patients with coagulopathy who are undergoing laparoscopic liver biopsy. METHODS Seventy-one patients (parts I and II) with advanced liver disease (Child-Turcotte B or C), platelet count > or =60,000/mm3, and PT in the range of 3-15 seconds above normal were included in the study. Efficacy endpoints were normalization of PT and time to hemostasis. RESULTS PT was corrected to normal levels (<13.1 seconds) in the majority of patients. The duration of normalization of PT was longer in patients treated with higher doses of rFVIIa. Forty-eight (74%) of 65 patients (part II) achieved hemostasis within 10 minutes. No correlation between the time to hemostasis and duration of correction of PT was observed. None of the patients required operative intervention or transfusion of blood/blood products to control bleeding. One thrombotic event and one case of disseminated intravascular coagulation were reported, but both events were considered by the investigator as unlikely to be related to treatment with rFVIIa. CONCLUSIONS The results of this study suggest that treatment with rFVIIa may offer benefit for patients with liver disease undergoing laparoscopic biopsy.