Topical rhThrombin as an Adjunct to Hemostasis During Segmental Hepatectomy

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

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

Study Overview

• Status: Completed
• Conditions: Hepatectomy
• Intervention / Treatment: Drug: rhThrombin ( Topical ); Drug: placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Zhiwei Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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;	Drug: rhThrombin ( Topical ); Active Substance; Other Names: Recombinant Human Thrombin (CHO Cell) for Topical Use
Placebo Comparator: 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;	Drug: placebo; saline solution; Other Names: PLA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of adverse events	Incidence and Severity of adverse events	baseline to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Achieving Hemostasis by Six Minutes After Treatment Start	Subjects achieving hemostasis at the target bleeding site by 6 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure	From start of treatment until 6 minutes after treatment start
The hemostatic time of the woud	The hemostatic time of the woud	From start of treatment until 6 minutes after treatment start
immunogenicity	Incidence of rhThrombin antibody and Confirm whether they are neutralizing antibody	baseline to 4 weeks

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Investigators: Principal Investigator: Zhiwei Li, PhD, The First Affiliated Hospital of Medical School of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2017
• Primary Completion (Actual): December 5, 2018
• Study Completion (Actual): July 30, 2019

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): August 2, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2021
• Last Update Submitted That Met QC Criteria: April 9, 2021
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Tolerance; Serine protease
• Additional Relevant MeSH Terms: Hemostatics; Coagulants; Thrombin
• Other Study ID Numbers: ZGrhT001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No