Prevention of Post-sphincterotomy Bleeding

Study Overview
=================
Brief Summary
-----------------
Background and Aim: Endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy (EST) are standard treatments for choledocholithiasis. However, 10% of post-EST bleeding was reported. Currently, there are no effective methods or medications for the prevention of post-EST bleeding. This study aimed to investigate whether the local administration of TXA and sucralfate can reduce the post-EST bleeding event. Methods: This is a randomized clinical trial. Patients with choledocholithiasis scheduled for ERCP with EST at National Cheng Kung University Hospital were enrolled. The study will recruit 60 patients. After randomization, 30 patients will be classified into the intervention group and 30 into the control group. The participants will receive standard ERCP and EST for common bile duct stone removal. If immediate polypectomy bleeding occurs, the investigators will apply standard endoscopic therapy by either local injection of diluted epinephrine or heater probe coagulation. After then, the investigators will spray 2g of sucralfate powder and 1g of tranexamic acid through duodenoscopy precisely on the post-EST wound in the intervention group. All enrolled patients will be monitored for delayed bleeding for 14 days after the ERCP.

Detailed Description
-----------------
Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure combining endoscopy and fluoroscopy to diagnose and treat diseases of the pancreaticobiliary ductal system, including choledocholithiasis, biliary strictures, and cholangitis. ERCP is associated with a higher rate of complications than other endoscopic procedures, including post-ERCP pancreatitis (PEP), bleeding, perforation, and biliary tract infection. The incidence rate of ERCP-related complications has been reported at approximately 10 percent, with mortality rates ranging from 0.1 to 1.4 percent. Despite recent technological advancements and safety precautions, the ERCP procedure-related death rates have remained high. Among all complications, delayed bleeding after sphincterotomy (EST) is a nightmare for both clinical physicians and endoscopists. Post-EST bleeding results in Tarry-bloody stool and anemia, increasing the mortality rate and hospital stay. While non-steroidal anti-inflammatory drugs (NSAIDs), pancreatic stents, and intravenous fluids can help prevent post-ERCP pancreatitis, there is no effective methodology or medication for bleeding prevention currently. Therefore, developing a prevention method for post-EST bleeding is urgent and important. Tranexamic acid (TXA) is a well-known antifibrinolytic agent that inhibits fibrin degradation by binding to tissue plasminogen, thereby preventing blood clot lysis and reducing bleeding. A recent study evaluating the effect of topical tranexamic acid (TXA) powder on bleeding peptic ulcers demonstrated that the precise endoscopic administration of TXA powder can enhance the stop-bleeding effect. Sucralfate, a complex of aluminum hydroxide and sucrose octa sulfate, can bind to the wound base. This protective barrier can prevent the wound from further environmental injury. Sucralfate has been widely used for wounds and ulcer treatment, e.g., skin wounds, oral ulcers, and peptic ulcers8. With the protective effect of the papilla mucosa, sucralfate can cover the EST wound and has the potential to avoid further environmental damage. In combination with TXA powder in stabilizing the clotting, we expect the post-EST bleeding event will reduce. Therefore, this study aimed to investigate whether the combination therapy of topical administration of TXA and sucralfate after EST can reduce the post-EST bleeding event.

Official Title
-----------------
Prevention of Post-sphincterotomy Bleeding by Endoscopic Tranexamic Acid and Sucralfate Administration: A Randomized Controlled Trial

Conditions
-----------------
Post-ERCP Bleeding

Intervention / Treatment
-----------------
* Drug: Sucralfate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged ≥ 18 years who accept ERCP and sphincterotomy for common bile duct (CBD) stone extraction Exclusion Criteria: Paitnets with no schedules for sphincterotomy Paitnets with unsuccessful CBD cannulation Patients with allergy to sucralfate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 95 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: Participants will be recruited from the volunteers with choledocholithiasis at National Cheng Kung University Hospital. Eligible participants include patients aged ≥ 18 years who accept ERCP and sphincterotomy for common bile duct (CBD) stone extraction. Patient consent forms will be given and explained to all patients before the ERCP. Exclusion criteria include patients with no schedules for sphincterotomy, unsuccessful CBD cannulation, and allergy to sucralfate.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>After the EST and stone extraction, we will randomly assign the patients to either a control or an intervention group. After EST, if immediate bleeding occurs, we will apply standard endoscopic therapy by either local injection of diluted epinephrine or heater probe coagulation. After then, we will spray 2g of sucralfate powder and 1g of tranexamic acid powder through a duodenoscope precisely on the EST wound in the intervention group. | Drug: Sucralfate<br>* 2g of sucralfate powder and 1g of tranexamic acid powder will be sprayed after EST<br>* Other names: Tranexamic acid;|
| No Intervention: Control group<br>After the EST and stone extraction, we will randomly assign the patients to either a control or an intervention group. After EST, if immediate bleeding occurs, we will apply standard endoscopic therapy by either local injection of diluted epinephrine or heater probe coagulation. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incident rate of delayed post-ERCP bleeding during the study period | The occurrence of delayed post-ERCP bleeding during the study period. Delayed post-ERCP bleeding was defined as remarkable hematochezia or Tarry stool with endoscopic evidence of post-EST wound bleeding. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incident rate of post-EST wound bleeding requiring transarterial embolization or emergency surgery | The incident rate of post-EST wound bleeding requiring transarterial embolization or emergency surgery. | 14 days | 
| The length of hospitalization | The length of hospitalization | 14 days | 
| The mortality rate | All-cause mortality after EST | 14 days | 
| The incident rate post-ERCP pancreatitis | The incident rate post-ERCP pancreatitis after ERCP. The definition is epigastric pain and elevated lipase. | 14 days |