Topical rhThrombin as an Adjunct to Hemostasis During Segmental Hepatectomy

Zelgen Biopharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hepatectomy

Treatments: Drug: placebo; Drug: rhThrombin ( Topical )

Study type: Interventional

Funder types: Industry

Identifiers

NCT03611426

ZGrhT001

Details and patient eligibility

About

rhThrombin is a serine protease from human.The study is to assess the Safety, Tolerability, Immunogenicity and efficacy of rhThrombin.

Full description

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.

Enrollment: 84 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male and female subjects between 18 and 75 years of age;
2. 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);
3. 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);
4. 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;
5. 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).
6. Patients have not used blood products in 24hours before surgery.
7. Meet the requirements of the ethics committee.Sign the informed consent form and visited according to the protocol.

Exclusion criteria

1. Blood system diseases are known, including coagulopathy or bleeding tendency;
2. Life signs were not stable for more than 24hours;
3. Severe heart、brain and blood vessel diseases in past 6 months,including TIA、Non-disabling cerebral infarction、myocardial infarction、unstable angina or Intracranial hemorrhage;
4. 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);
5. Complicated with other serious diseases(active infections,uncontrolled diabetes and hyperthyroidism);
6. Be allergic to thrombin(human)、serum(snake) and proteins (hamster);
7. Female subjects are in lactation or serum pregnancy test are positive;
8. Take part in other clinical trail within 4 weeks before geting into the study;
9. Using the Thrombin products and Antithrombin antibodies or Coagulation V factor antibodies are positive before, after using rhthrombin, it may generate an immune response.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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84 participants in 2 patient groups, including a placebo group

rhThrombin ( Topical )

Experimental group

Description:

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;

Treatment:

Drug: rhThrombin ( Topical )

placebo

Placebo Comparator group

Description:

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;

Treatment:

Drug: placebo