Efficacy of Hemostatic Powder in Preventing Bleeding After Gastric Endoscopic Submucosal Dissection in High-risk Patients: A Prospective Randomized Control Study

Study Overview
=================
Brief Summary
-----------------
Endoscopic submucosal dissection (ESD) for superficial gastric neoplasm is minimally invasive and achieves curative resection with an acceptable rate of adverse events. Although the safety of ESD has been demonstrated, the procedure is associated with a substantial risk of adverse events, including bleeding, perforation, and stricture. Post-ESD bleeding is the most frequent adverse events and the incidence of post-ESD bleeding in previous studies ranges from 1.8% to 15.6%. Several studies identified that antithrombotic agents and large resection size were strong risk factors for post-ESD bleeding. Moreover, the incidence of bleeding in high-risk patients has been reported to be as high as 61.5%, depending on the definition of high-risk patients. The number of patients at high risk for post-ESD bleeding is increasing worldwide. In addition, as the indications for ESD have been expanding, more patients with large lesions undergo ESD. Therefore, it is important to prevent post-ESD bleeding in high-risk patients. Although several previous studies have attempted to prevent post-ESD bleeding using surgical material, there is no definite prophylactic treatment to prevent re-bleeding after ESD. To date, coagulation of remnant vessels on the post-resection ulcer surface and administration of a proton pump inhibitor (PPI) after ESD are practical methods to prevent post-ESD bleeding. Polysaccharide hemostatic powder (Endo-Clot™) is a new topical hemostatic method recently used for non-variceal upper gastrointestinal bleeding. This study aimed to identify the efficacy of hemostatic powder in preventing post-ESD bleeding in high-risk patients. This is a multicenter, prospective, randomized study.

Detailed Description
-----------------
A multicenter, prospective, randomized controlled study High-risk patients of post-ESD bleeding will be prospectively enrolled in the study. High-risk of post-ESD bleeding is defined as patients with taking antithrombotic agents or with large resection (specimen size ≥ 40mm). All ESDs were performed according to the standard procedure sequence in the hemostatic powder group and control group. The Only difference between two groups was hemostatic powder (Endo-clot™) application after standard hemostasis using hemostatic forceps in the hemostatic powder group. For patients in the study group, after hemostasis on the post-resection ulcer using conventional method and removal of specimen, Endo-clot™ (EndoClot Plus, Unc., Santa Clara, CA, USA) was applied immediately onto the post-resection surface. Bleeding rate of study group within 4 weeks after ESD will be compared with the control group. 

Official Title
-----------------
Efficacy of Hemostatic Powder in Preventing Bleeding After Gastric Endoscopic Submucosal Dissection in High-risk Patients: A Prospective Randomized Control Study

Conditions
-----------------
High-risk Patients for Post-ESD Bleeding

Intervention / Treatment
-----------------
* Procedure: Endo-clot™ (EndoClot Plus, Unc., Santa Clara, CA, USA) group
* Procedure: Hemostatic forceps Only (Coagrasper®, Olympus, Japan) group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Older than 19 years old and younger than 85 years old Pathologically confirmed gastric adenoma and/or early gastric cancer Iatrogenic gastric ulcer after ESD (Endoscopic submucosal dissection) more than 40mm (at prediction) Patients who is taking antithrombotic drug such as aspirin and/or coumadin (and other anti-coagulation medication) ECOG performance status 0 or 1 Adequate renal function (serum creatinine < 1.5 mg/dL or calculated creatinine clearance ≥ 60 ml/min) Adequate liver function (total bilirubin < 1.5 X the upper limits of normal (ULN), AST and ALT <3 X UNL, and alkaline phosphatases < 3 X ULN or < 5 x ULN in case of liver involvement) Adequate BM function (WBC ≥ 3,500/µl, absolute neutrophil cell count ≥ 1,500 /µl, platelet count ≥ 100,000/µl) Subjects who given written informed consent after being given a full description of the study Exclusion Criteria: Previously treated by radical gastrectomy Adverse effect on this medication Pregnant or on breast feeding Patients who are unwilling or unable to provide informed consent, such as those with psychiatric problem, drug abuse or alcoholism

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All procedures were performed according to the standard procedure sequence in the hemostatic powder group and control group. The Only difference between two groups was hemostatic powder (Endo-clot™) application after standard hemostasis using hemostatic forceps in the hemostatic powder group. For patients in the study group, after hemostasis on the post-resection ulcer using conventional method and removal of specimen, Endo-clot™ (EndoClot Plus, Unc., Santa Clara, CA, USA) was applied immediately onto the post-resection surface.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemostatic powder group (Endo-clot™ group)<br>Patients who will undergo ESD with Endo-clot™ (EndoClot Plus, Unc., Santa Clara, CA, USA) after hemostasis on the post-resection ulcer using conventional method and removal of specimen. | Procedure: Endo-clot™ (EndoClot Plus, Unc., Santa Clara, CA, USA) group<br>* For patients in the study group, after hemostasis on the post-resection ulcer using conventional method and removal of specimen, Endo-clot™ (EndoClot Plus, Unc., Santa Clara, CA, USA) was applied immediately onto the post-resection surface.<br>* Other names: Endo-clot™ group;|
| Active Comparator: Hemostatic forceps Only (Coagrasper®, Olympus, Japan) group<br>For patients in the control group, hemostasis with conventional method (electrical coagulation and/or clip, Coagrasper®, Olympus, Japan) will be done. | Procedure: Hemostatic forceps Only (Coagrasper®, Olympus, Japan) group<br>* All ESDs were performed according to the standard procedure sequence in the hemostatic group and control group except hemostatic powder application.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding rate until 4 weeks after ESD | Post-ESD bleeding was defined by clinical symptoms or laboratory findings. Clinical symptoms such as melena, hematemesis were defined as bleeding signs. A decrease of hemoglobin of 2.0 g/dL was defined as laboratory bleeding sign. | until 4 weeks after ESD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding rates according to the timing | early bleeding: 0 48 hours after ESD late bleeding: 2 days   4 weeks after ESD | within 48 hours from 2 days to 4 weeks after ESD | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hemostatic powder, post-ESD bleeding, antithrombotic therapy, high risk of bleeding, endoscopic submucosal dissection, adverse event