A Randomized，Ascending Dose，Single-blind Phase 1&2 Study to Evaluate the Safety, Tolerability, Immunogenicity and Efficacy of Topical rhThrombin as an Adjunct to Hemostasis During Segmental Hepatectomy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Incidence and Severity of adverse events
研究概览
简要总结
rhThrombin is a serine protease from human.The study is to assess the Safety, Tolerability, Immunogenicity and efficacy of rhThrombin.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
rhThrombin ( Topical )
Cohort 1:rhThrombin ( Topical ) 500IU /ml、1000IU/m and 2000IU/ml During segmental hepatectomy; Cohort 2:rhThrombin ( Topical ) 1000IU/m and 2000IU/ml with absorbable collagen sponge During segmental hepatectomy; Cohort 3:rhThrombin ( Topical ) 1000IU/m and 2000IU/ml used directly sprayed on hemorrhagic point During segmental hepatectomy;
干预措施: rhThrombin ( Topical ) (Drug)
placebo
Cohort 1: the same volume of saline during segmental hepatectomy; Cohort 2:the same volume of saline used withabsorbable collagen sponge during segmental hepatectomy; Cohort 3:the same volume of saline during segmental hepatectomy;
干预措施: placebo (Drug)
结局指标
主要结局
Incidence and Severity of adverse events
时间窗: baseline to 4 weeks
Incidence and Severity of adverse events
次要结局
- The hemostatic time of the woud(From start of treatment until 6 minutes after treatment start)
- Proportion of Subjects Achieving Hemostasis by Six Minutes After Treatment Start(From start of treatment until 6 minutes after treatment start)
- immunogenicity(baseline to 4 weeks)