Topical rhThrombin as an Adjunct to Hemostasis During Segmental Hepatectomy

The study is a randomized, single-blind,blank controlled phase 1&2 trial ,including 3 independent parts toevaluate the safety,efficacy and immunogenicity.

The first part is ascending dose,blank control tolerability and safety study. The Starting doses from 500IU/ml to 1000IU/mL and 2000IU/mL to evaluate the safety,efficacy.

The second part is randomized, single-blind, blank controlled study to evaluate safety、efficacy and immunogenicity. Doses settings :1000IU/mL , 2000IU/mL and blank group which with absorbable collagen sponge when used.

The third part is randomized, single-blind, blank controlled study to evaluate safety、efficacy and immunogenicity. Doses settings :1000IU/mL , 2000IU/mL and blank group which directly sprayed on hemorrhagic point when used.

Inclusion criteria

• Male and female subjects between 18 and 75 years of age;
• Hepar wedge resection or anatomic hepatectomy(one to five continue hepatic segments) (remark:including open surgery or hand-assisted laparoscopic surgery,patients who has been cholecystectomy or choledochotomy can be also get into the study);
• Blood routine(including WBC、ANC、RBC、Hb and PLT) and Liver function(ALT≤1.5ULN、AST≤1.5ULN) is appear normal. ALP、LDH、 TBil、Dbil are normal.(Remark: Patients whose Laboratory tests are abnormal but they are no clinical significance can get into the study);
• Renal function(including Cr、BUN)、coagulation function（including PT、APTT、TT、INR）、 electrolytes（include K、Na、CL、Ca、P、Mg）and electrocardiogram are normal or anormal.Investigator think they make no difference to operation;
• No other therapeutic surgery was performed in the first 4 weeks before the subject gets into clinical research the study(in addition to diagnostic surgery).
• Patients have not used blood products in 24hours before surgery.
• Meet the requirements of the ethics committee.Sign the informed consent form and visited according to the protocol.

Exclusion criteria

• Blood system diseases are known, including coagulopathy or bleeding tendency;
• Life signs were not stable for more than 24hours;
• Severe heart、brain and blood vessel diseases in past 6 months,including TIA、Non-disabling cerebral infarction、myocardial infarction、unstable angina or Intracranial hemorrhage;
• Using the drugs that have an effect on blood coagulation in 7 days before surgey(including but not limited to: aspirin、clopidogrel、ticlopidine、dipyridamole、ginkgo biloba extract、heparin、warfarin、citrates、hemocoagulase、VitK、ethamsylate and Vitc,etc);
• Complicated with other serious diseases(active infections,uncontrolled diabetes and hyperthyroidism);
• Be allergic to thrombin(human)、serum(snake) and proteins (hamster);
• Female subjects are in lactation or serum pregnancy test are positive;
• Take part in other clinical trail within 4 weeks before geting into the study;
• Using the Thrombin products and Antithrombin antibodies or Coagulation V factor antibodies are positive before, after using rhthrombin, it may generate an immune response.