Safety and Efficacy of Topical Recombinant Human Thrombin(rhThrombin) for Surgical Hemostasis

A Phase 3, Stratified Randomized, Double-blind, Placebo-controlled Study of Topical Recombinant Human Thrombin (rhThrombin) in Surgical Hemostasis

A multicenter, stratified randomized, double-blind, placebo-controlled, phase 3 clinical trial.

Study Overview

• Status: Completed
• Conditions: Surgical Hemostasis
• Intervention / Treatment: Biological: recombinant human Thrombin(CHO cell); Biological: placebo

Detailed Description

After establishing eligibility, subjects will be randomized in a 2:1 ratio to receive rhThrombin (1000 U/mL) or placebo. During a surgical procedure, study participants will be treated with blinded study drug (rhThrombin or placebo) in combination with an absorbable gelatin sponge at appropriate bleeding evaluation site(s). 510 patients will participate in the study.

In this study, stratified random enrollment was conducted according to the condition(experimental group or control group) of the subjects.Stratification factors were centered, gender (male/female) and age (18 ≤ age <60/60 ≤ age ≤70).

• Study Type: Interventional
• Enrollment (Actual): 348
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 70 years old (including 18 and 70 years old), male or female;
• Patients with wedge-shaped liver resection or anatomical liver resection(1-5 consecutive liver segments);
• After the operation was controlled by standard surgical hemostasis, there were still patients with mild/moderate bleeding lesions (bleeding, non-arterial bleeding);
• Electrolytes (K, Na, CL, Ca, P, Mg) and ECG are normal or abnormal, Investigators believe that patients who do not affect surgery
• No other therapeutic surgery within 4 weeks before enrollment;
• Patients who have not used blood products within 24 hours before surgery;
• In compliance with the requirements of the ethics committee, patients voluntarily signed informed consent and were able to conduct visits as required by the protocol.

Exclusion Criteria:

• Known diseases of the blood system, including patients with coagulopathy or bleeding tendency;
• Patients with unstable vital signs for more than 24 hours;
• A history of severe heart, brain, and vascular disease within 6 months, including patients with a history of TIA, non-disabling cerebral infarction, myocardial infarction, unstable angina, or intracranial hemorrhage;
• Active bleeding or abnormal coagulation function (PT>16s, APTT>43s, INR≥2) or receiving thrombolysis, anticoagulation or antiplatelet therapy;
• Have used drugs that affect the function of the coagulation system within 1 week before surgery (including but not limited to: aspirin, clopidogrel, ticlopidine, fensulfamide, desmopressin, aminotoluic acid, dipyridamole, ginkgo Leaf preparations, heparin, warfarin, citrate, hemagglutinin, Vk, anti-fibrotic solvents, hemostatic, Vc, etc.);
• Women during pregnancy and lactation;
• Participants who participated in clinical trials of other drugs within 4 weeks before enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The experimental group; The topical recombinant human thrombin(rhThrombin) was prepared into 1000IU/mL solution with 10ml normal saline and used in combination with absorbable gelatin spongeat at appropriate bleeding evaluation site(s).	Biological: recombinant human Thrombin(CHO cell); 2 rhThrombin, dissolved in 5mL sterile saline and mixed, the final solution contains 1000IU/mL rhThrombin solution (clear and transparent liquid).; Other Names: rhThrombin
Placebo Comparator: The control group; The placebo was prepared into a solution with 10mL normal saline and used in combination with absorbable gelatin sponge at appropriate bleeding evaluation site(s).	Biological: placebo; placebo, dissolved in 5mL sterile saline and mixed, the final solution contains 1000IU/mL rhThrombin solution (clear and transparent liquid).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of complete hemostasis within 6 minutes.	Those who did not stop bleeding within 6 minutes were defined as treatment failure.	6 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events(AE)	An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment.	Up to 28 days
Time to Hemostasis(TTH)	TTH will be assessed for up to 6 minutes	Evaluate the effect of hemostasis every 30sec until hemostasis is completed or 6 minutes of observation is completed
Immunogenicity	Positive rate of anti-recombinant human thrombin neutralizing antibody.	At baseline and Day 29

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Investigators: Principal Investigator: Sheng Yan, PhD, The First Affiliated Hospital, Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Actual): October 20, 2021
• Study Completion (Actual): October 20, 2021

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: hepatic resection; rhThrombin,topical
• Additional Relevant MeSH Terms: Hemostatics; Coagulants; Thrombin
• Other Study ID Numbers: ZGrhT002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No