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

Phase 3

Completed

• Conditions: Surgical Hemostasis
• Interventions: Biological: recombinant human Thrombin(CHO cell); Biological: placebo

• Registration Number: NCT04459871
• Lead Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Brief Summary

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

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 Timeline

• Study Start: 2019-11-11
• Study First Submitted: 2020-07-01
• Study First Submitted QC: 2020-07-06
• Study First Posted: 2020-07-07
• Primary Completion: 2021-10-20
• Study Completion: 2021-10-20
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-28
• Last Update Posted: 2022-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 348

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
The experimental group	recombinant human Thrombin(CHO cell)	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).
The control group	placebo	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).

Primary Outcome Measures

Name	Time	Method
The rate of complete hemostasis within 6 minutes.	6 minutes	Those who did not stop bleeding within 6 minutes were defined as treatment failure.

Secondary Outcome Measures

Name	Time	Method
Immunogenicity	At baseline and Day 29	Positive rate of anti-recombinant human thrombin neutralizing antibody.
Time to Hemostasis(TTH)	Evaluate the effect of hemostasis every 30sec until hemostasis is completed or 6 minutes of observation is completed	TTH will be assessed for up to 6 minutes
Incidence of adverse events(AE)	Up to 28 days	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.

Trial Locations

Locations (1)

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China