Early Selective TAE to Severely Bleeding Peptic Ulcers After Their Initial Endoscopic Hemostasis

Early Selective Angiographic Embolization to Severely Bleeding Peptic Ulcers After Their Initial Endoscopic Hemostasis - a Randomized Controlled Trial

The aim of this study is to determine if early angiographic embolization can forestall recurrent bleeding in selected high risk ulcers after their initial endoscopic control; to validate prospectively the investigators proposed in selecting high risk ulcers for recurrent bleeding in spite of maximal endoscopic control and profound acid suppression using high dose intravenous infusion of proton pump inhibitor; to characterize the nature of bleeding arteries in severely bleeding peptic ulcers and determine the efficacy of angiographic embolization in the prevention of recurrent bleeding and to establish safety profile of angiographic embolization as an early elective treatment to bleeding peptic ulcers.

Study Overview

• Status: Completed
• Conditions: Bleeding; Peptic Ulcer; Arterial Embolization
• Intervention / Treatment: Procedure: TAE; Procedure: No TAE

Detailed Description

Endoscopic therapy is now the treatment of choice in patients with actively bleeding peptic ulcers and ulcers with non-bleeding visible vessels. Following endoscopic control of bleeding, we showed that the use of a high dose intravenous infusion of proton pump inhibitor (PPI) for 72 hours further reduced rate of recurrent bleeding [Lau NEJM 2000]. Recurrent bleeding still occurs in 8 to 10 percent of patients who receive the above treatment regime. The associated mortality following a rebleed is 4-10 fold higher when compared to those without recurrent bleeding. In a logistic regression model involving 1144 patients after successful endoscopic thermocoagulation to their bleeding peptic ulcers, we demonstrated that several factors independently predicted recurrent bleeding. They included hypotension, hemoglobin <10g/dl, fresh blood in the stomach, ulcer size > 2cm and active bleeding during endoscopy [Wong Gut 2003]. When we applied this model in a cohort of 945 patients who underwent endoscopic control of bleeding to their ulcers and adjunctive use of high dose intravenous PPI, 275 belonged to the high risk group. Of them, rebleeding leading to surgery or death occurred in 46 patients (16.7%)[Chiu DDW 2007]. Endoscopic treatment to bleeding peptic ulcers has its own limit. In an ex vivo bleeding model using canine mesenteric arteries, endoscopic thermocoagulation could only consistently seal arteries up to 2 mm in size [Johnson Gastro 1987]. Trans-arterial angiography allows clinicians to study and characterize bleeding arteries underneath peptic ulcers. In ulcers that erode into major arteries such as the gastro-duodenal artery complex and branches from left gastric artery, angiography complements endoscopic therapy in the form of selective coiling of the bleeding artery. Trans-arterial angiographic coiling can provide definitive control of bleeding from larger arteries i.e. > 2 mm in size. In cohort studies, trans-arterial angiographic coiling has been shown to compare favorably to surgery, and is less invasive in the control of severe bleeding in peptic

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Endoscopy Centre, Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Actively bleeding peptic ulcers (Forrest I), NBVV or Forrest IIa ulcer,
• Successful endoscopic hemostasis by combination treatment of injected epinephrine followed by either 3.2mm heat probe 30J (4 continuous pulses) or hemo-clipping (at least 2 clips) And one of the followings
• Spurting hemorrhage during endoscopy;
• Ulcer >= 2 cm is determined by an opened biopsy forceps;
• Hb on admission of < 9 g/dl; or
• Hypotension prior to endoscopy defined by SBP of <90 mmHg AND HR of >110 bmp

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TAE group; Patients will be undergone TAE after endoscopic hemostasis.	Procedure: TAE; The procedure will be performed within 12 hours of endoscopic therapy. This is usually performed under conscious sedation; Other Names: Transarterial embolization
Active Comparator: No TAE group; No TAE procedure will be performed after endoscopic treatment.	Procedure: No TAE; No TAE procedure will be performed after endoscopic treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical re-bleeding	Clinical rebleeding is defined by fresh hematemesis, fresh melena or hematochezia and signs of hypovolemic shock (systolic blood pressure of <90mmHg and pulse rate >110 per minute) and a drop in hemoglobin of > 2 g/dl per 24 hours despite adequate transfusion. Rebleeding will be confirmed by an immediate endoscopy showing fresh blood in stomach or active bleeding from a previously seen ulcer. A clinical rebleeding will be independently reviewed by an adjudication panel.	within 30 days of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death from all causes	death from all causes	within 30 days of therapy
transfusion requirement	transfusion requirement	within 30 days of therapy
hospital stay including Intensive Care Unit stay	hospital stay including Intensive Care Unit stay	within 30 days of therapy
further interventions either further TAE or surgery	further interventions either further TAE or surgery	within 30 days of therapy
hospital costs	hospital costs	within 30 days of therapy

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: King Chulalongkorn Memorial Hospital
• Investigators: Principal Investigator: James Y Lau, MD, Chinese University of Hong Kong

Publications and helpful links

General Publications

• Lau JYW, Pittayanon R, Wong KT, Pinjaroen N, Chiu PWY, Rerknimitr R, Holster IL, Kuipers EJ, Wu KC, Au KWL, Chan FKL, Sung JJY. Prophylactic angiographic embolisation after endoscopic control of bleeding to high-risk peptic ulcers: a randomised controlled trial. Gut. 2019 May;68(5):796-803. doi: 10.1136/gutjnl-2018-316074. Epub 2018 May 25.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: June 9, 2010
• First Submitted That Met QC Criteria: June 10, 2010
• First Posted (Estimate): June 11, 2010

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Bleeding peptic ulcer; Active bleeding; Trans-arterial angiographic embolization
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Duodenal Diseases; Gastrointestinal Hemorrhage; Ulcer; Hemorrhage; Peptic Ulcer; Peptic Ulcer Hemorrhage
• Other Study ID Numbers: TAE2