Clinical trial NCT06196710: The Use of OTSC in LBGDU to Standard Endoscopic Hemostatic Methods
Official title: The Use of Over-the-scope-clips in Large Bleeding Gastro-duodenal Ulcers; a Randomized Comparison to Standard Endoscopic Hemostatic Methods
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Bleeding Peptic Ulcer
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: King Chulalongkorn Memorial Hospital
name: West China Hospital
name: Beijing Friendship Hospital
name: Nanfang Hospital, Southern Medical University
name: The First Affiliated Hospital of Nanchang University
First posted: 2024-01-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 111
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are randomized in a 1:1 ratio to receive; endoscopic treatment using OTSC or standard therapies.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: bleeding free probability in 30 days after randomization
timeFrame: 30 days
Secondary outcomes:
measure: failure to control bleeding with assigned endoscopic treatment and recurrent bleeding after initial hemostasis
timeFrame: 30 days
measure: number of participants using angiographic treatment
timeFrame: 30 days
measure: number of participants using surgical treatment
timeFrame: 30 days
measure: second endoscopic attempts at hemostasis
timeFrame: 30 days
Other outcomes:
measure: red cell transfusion
timeFrame: 30 days
measure: number of days in the hospital
timeFrame: 30 days
measure: number of days in intensive care unit (ICU)
timeFrame: 30 days
measure: rate of bleeding-related or all-cause deaths
timeFrame: 30 days
Locations:
Study officials:
affiliation: Chinese University of Hong Kong
name: YUN WONG LAU
role: PRINCIPAL_INVESTIGATOR
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