The Use of OTSC in LBGDU to Standard Endoscopic Hemostatic Methods (OTSC-LBGDU)

January 22, 2025 updated by: James Yun-wong Lau, MD, Chinese University of Hong Kong

The Use of Over-the-scope-clips in Large Bleeding Gastro-duodenal Ulcers; a Randomized Comparison to Standard Endoscopic Hemostatic Methods

In managing bleeding gastroduodenal ulcers, endoscopic control of bleeding is the first line treatment-further bleeding after endoscopic hemostasis is associated with a 3-fold increase in mortality. Large ulcer size (> 20 mm) predicts further bleeding. These ulcers erode into arteries of significant size (>2 mm) from either the gastro-duodenal or left gastric arterial complexes. An over-the-scope clip is an endoscopic clamp device with a high tensile strength. It can compress sizeable arteries, and firmly anchor onto the ulcer base avoiding recurrent bleeding from clip dislodgement. It therefore offers secure and durable hemostasis.

In the proposed randomized controlled trial, the investigators hypothesize that after initial endoscopic control of bleeding from large gastro-duodenal ulcers (20 mm in size or more), adding an OTSC can prevent recurrent bleeding and improve patients' outcomes. Investigators enroll patients with bleeding from large ulcers as defined. After initial endoscopic control of bleeding using injection with diluted epinephrine, these patients are randomized, during endoscopy, to receive standard treatment (thermo-coagulation or hemo-clips) or an added OTSC. The primary endpoint is recurrent bleeding over 30 days confirmed on endoscopy. Secondary endpoints include the need for rescue treatment; endoscopic, angiographic embolization or surgery, red blood cell (RBC) transfusion, hospitalization, and bleeding related and all-cause mortality.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Endoscopic hemostatic treatment is the cornerstone of the management of patients with acute nonvariceal upper gastrointestinal bleeding. The current standard in endoscopic hemostasis includes the use of hemo-clips or contact thermal devices with or without pre-injection with diluted epinephrine. However, the failure rate with either method approaches 10%. Further bleeding after endoscopic treatment is associated with a 3-fold increase in mortality. The United Kingdom audit reported a 30% mortality in those who required surgery after failed endoscopic treatment.

Over-the-scope clips (OTSCs) are memory-shaped nitinol clips that are cap-mounted onto the end of an endoscope. They were designed for endoscopic closure of full-thickness mucosal defects. They are being increasingly used for the purpose of hemostasis. When deployed, the OTSC provides firm compression on bleeding vessels of significant sizes (>2mm). The retention rate with OTSCs is high avoiding recurrent bleeding from clip dislodgement.

The OTSCs were first evaluated as a rescue treatment in the German Multicenter Trial (Stop the Bleeding or STING 1 trial). The trial enrolled patients with bleeding from their ulcers refractory to standard endoscopic treatment and randomized them to receive either OTSC or further treatment with standard methods. Further bleeding within 30 days after either treatment was 15.2% and 57.6% respectively.

The primary use of OTSC i.e. as the first hemostatic device has been studied in several trials. (see Table 1).

Table 1: Further bleeding in 30 days Author, Year OTSC Standard Treatment

Jensen 2021 1 /25, 4% 8/ 28, 28.6%

Meier 2022 4/ 44, 8.3% 14/ 52, 26.9%

Chan 2023 (ulcers 15 mm or more) 5/ 50, 10% 9/ 50, 18%

Lau 2023 3/ 93, 3.2% 14/ 97, 14.6%

All of the above studies except one showed significant differences in the rate of further bleeds within 30 days in favor of the use of OTSC.

The role of OTSCs in larger gastroduodenal ulcers remains inconclusive. Chan studied exclusively ulcers of 15 mm or above in size. In this study, the use of OTSC did not significantly reduce further bleeds compared to standard treatment (rate of further bleeding 10% vs. 18%). There may have been two reasons to explain a negative trial; first, there were 4 primary failures with the use of OTSC (4/ 50, 8%). Two OTSCs did not fully encompass the vessels. In 2 cases, there were persistent bleeds despite the placement of OTSCs. The authors attributed the failure with the use of OTSC to a learning curve issue. Recurrent bleeds occurred in 2 of 46 (4.4%) after OTSC and 9 of 48 (18.8%) after standard treatments. Because of a small sample size and likely a type 2 error, the overall difference did not reach statistical significance. Gastroduodenal ulcers of 20 mm or more in size are the most critical predictor of further bleeds and failures with endoscopic treatment. These ulcers erode into major arterial complexes to the gastroduodenal and left gastric arteries. An OTSC appears to work well in such ulcers. In a post hoc analysis of our randomized controlled trial (RCT) on the primary use of OTSCs, further bleeds among ulcers 20 mm or larger occurred in 1 of 10 after OTSC treatment compared to 5 of 9 after standard treatment. Because of the inconclusive and conflicting results from the above trials regarding the efficacy of OTSC in high-risk (20mm or larger in size) bleeding gastroduodenal ulcers, investigators propose a randomized controlled trial with the hypothesis that OTSC is superior to standard treatment in bleeding gastroduodenal ulcers 20mm or greater in size. Investigators argue that OTSC should be the primary treatment of choice for ulcers of such size.

Research methods Trial Design and Organisation This study is an investigator-initiated multicentre trial. The participating centers are tertiary referral university hospitals with a high case volume. These include the Prince of Wales Hospital, Hua-Xi Hospital of Szechuan University, Beijing Friendship Hospital, the first affiliated Hospital of Nanchang University, Nanfang Hospital from China, and the King Chulalongkorn Memorial Hospital in Thailand. These hospitals have substantial experience with the use of OTSC and participated in earlier and ongoing clinical trials that evaluate the use of OTSC.

Investigators will obtain approval from the institutional review board in each participating hospital.

The joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee oversees the trial execution. Senior physicians from the committee adjudicate outcomes and review serious adverse events.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • patients admitted with acute upper gastrointestinal bleeding (melena, hematemesis, or decrease in hemoglobin level with or without hypotension).
  • large gastro-duodenal ulcers (20 mm in size or more)
  • active bleeding (pulsatile or Forrest Ia bleeding, oozing from a visible vessel, or Forrest Ib bleeding) or a nonbleeding visible vessel (Forrest IIa lesion). Clots overlying bleeding lesions are injected with diluted epinephrine and then irrigated or elevated using a cheese-wiring technique. If a vessel is then unveiled, we can proceed with randomization.

Exclusion Criteria:

  • patients with esophagogastric varices
  • pregnant or lactating women
  • patients who cannot provide written consent
  • moribund from their co-morbid illnesses and are not considered for active treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Over-the-scope Clips
Endoscopic Application of Over-the-scope Clips
Device: Over-the-scope Clips
Over-the-scope Clips is mounted onto a transparent cap, which is attached to the tip of the endoscope. To deploy the claw device, a cogwheel at the scope head is turned pulling a trip string. This in turn retracts the cap releasing the OTSC onto the vessels.
Other Names:
  • OTSC
Active Comparator: standard treatment
standard treatment of either hemo-clipping or thermo-coagulation with or without pre injection with diluted epinephrine <=20 clips or pulse
Device: Hemo-clipping
Contact thermocoagulation using a 3.3mm probe, hemo-clips, or both. The use of the bipolar device involves firm mechanical compression and coagulation for about 8 seconds.
Other Names:
  • quick clips
  • thermo-coagulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
bleeding free probability in 30 days after randomization
Time Frame: 30 days
further bleeding defined by the composite of failure to control bleeding after assigned endoscopic treatment and recurrent bleeding.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
second endoscopic attempts at hemostasis
Time Frame: 30 days
attempts at hemostasis if primary failure or rebleeding.
30 days
failure to control bleeding with assigned endoscopic treatment and recurrent bleeding after initial hemostasis
Time Frame: 30 days
failure to control bleeding during the first endoscopy was defined as persistent or active bleeding after the attempted application of assigned endoscopic treatment. Recurrent bleeding was defined by fresh hematemesis, fresh melena, or hematochezia with hemodynamic instability (systolic blood pressure <90 mm Hg, heart rate >110 beats/min), and/or decrease in hemoglobin level greater than 20 g/L in 24 hours after transfusion to around 80 g/L. Patients who fulfill the clinical criteria of recurrent bleeding undergo urgent endoscopy. Recurrent bleeding requires endoscopic confirmation showing fresh blood in the gastroduodenal tract and active bleeding from a previously treated ulcer.
30 days
number of participants using angiographic treatment
Time Frame: 30 days
angiogram with embolization to bleeding vessel if primary failure or rebleeding
30 days
number of participants using surgical treatment
Time Frame: 30 days
surgical treatment if primary failure or rebleeding
30 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
red cell transfusion
Time Frame: 30 days
amount of total blood transfusion
30 days
number of days in the hospital
Time Frame: 30 days
hospital stay
30 days
number of days in intensive care unit (ICU)
Time Frame: 30 days
ICU stay
30 days
rate of bleeding-related or all-cause deaths
Time Frame: 30 days
bleeding-related or all-cause mortality
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Collaborators

The First Affiliated Hospital of Nanchang University
Beijing Friendship Hospital
West China Hospital
King Chulalongkorn Memorial Hospital
Nanfang Hospital, Southern Medical University

Investigators

  • Principal Investigator: YUN WONG LAU, Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2025

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

December 26, 2023

First Submitted That Met QC Criteria

December 26, 2023

First Posted (Actual)

January 9, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 22, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OTSC-LBGDU

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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