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Over-the-scope Clips and Standard Treatments in Endoscopic Control of Acute Bleeding From Non-variceal Upper GI Causes

Primary Purpose

Acute Upper Gastrointestinal Bleeding, Tumor Bleeding

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Over-the-scope Clips
Hemo-clipping
thermo-coagulation
Epinephrine
Sponsored by
Chinese University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Upper Gastrointestinal Bleeding

Eligibility Criteria

18 Years - 111 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with overt signs of acute upper GIB (melena, hematemesis, drop in hemoglobin with or without hypotension)
  • documented bleeding lesions suitable for standard endoscopic treatment during endoscopy

Exclusion Criteria:

  • without a full informed consent from the patient or his legally-acceptable representatives
  • Age <18 years
  • Pregnant
  • Lactating women
  • Moribund patients not considered for active treatment.

Sites / Locations

  • Sunshine Hospital
  • Footscray Hospital
  • Beijing Friendship Hospital
  • The First Affliated Hospital of SooChow University
  • The First Affliated Hospital, Zhejiang University
  • Ningbo First Hospital
  • Endoscopy Centre, Prince of Wales Hospital
  • Queen Mary Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Over-the-scope Clips

standard treatment

Arm Description

Endoscopic Application of Over-the-scope Clips

standard treatment of either hemo-clipping or thermo-coagulation with or without pre injection with diluted epinephrine <=20 clips or pulse

Outcomes

Primary Outcome Measures

Bleeding free probability in 30 days after randomization
Further bleeding is defined by failure to control bleeding during first endoscopy or recurrent bleeding after initial control.

Secondary Outcome Measures

re-interventions in the form of endoscopic
heater probe or clips endoscpic therapy
angiographic treatment
angiopgram with embolization to bleeding vessel
surgical treatment
surgical treatment if primary failure or rebleeding
blood transfusion 4. blood transfusion blood transfusion
amount of total blood transfusion
adverse events
adverse events (related or unrelated to endoscopic treatment)
mortality
deaths from all causes
cost analysis (Based on the cost data from the Hospital
Authority Gazette, Hong Kong Special Administrative Region Government; the investigator will calculate cost to avert one episode of further clinical bleeding with the use of OTSC or standard treatment. A series of sensitivity analyses varying device costs and over a range of re-bleeding rates.)

Full Information

First Posted
July 11, 2017
Last Updated
July 26, 2021
Sponsor
Chinese University of Hong Kong
Collaborators
Queen Mary Hospital, Hong Kong, The First Affiliated Hospital of Soochow University, Beijing Friendship Hospital, Zhejiang University, Ningbo No. 1 Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03216395
Brief Title
Over-the-scope Clips and Standard Treatments in Endoscopic Control of Acute Bleeding From Non-variceal Upper GI Causes
Official Title
Over-the-scope Clips and Standard Treatments in Endoscopic Control of of Acute Bleeding From Non-variceal Upper GI Causes(OTSC Study)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
January 2, 2018 (Actual)
Primary Completion Date
January 16, 2021 (Actual)
Study Completion Date
January 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese University of Hong Kong
Collaborators
Queen Mary Hospital, Hong Kong, The First Affiliated Hospital of Soochow University, Beijing Friendship Hospital, Zhejiang University, Ningbo No. 1 Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In the management of patients with acute upper gastrointestinal bleeding from non-variceal causes, endoscopic treatment and acid suppression are now the standard of care. Current endoscopic treatment in the form of either thermo-coagulation or clipping to the bleeding arteries is highly efficacious in the stopping bleeding. Unfortunately in 5 to 10% of patients, bleeding cannot be controlled during index endoscopy or recurs after initial hemostasis. These patients are often elderly with significant co-morbidities. Their bleeding lesions are large eroding into major sub-serosal arteries. In the few who need surgical salvage, mortality increases to around 30%. The Over-the-scope-Clip (OTSC) is a device, which allows endoscopists to capture a large amount of tissue and compress on the bleeding artery. The OTSC also has a high retention rate. Recurrent bleeding with the use of standard hemo-clips can occur because of their low retention rate. We reported the use of OTSC with a high success rate in a case series of patients with refractory bleeding after standard endoscopic treatment. We have also used OTSC in the treatment of bleeding from pseudo-aneurysm arising from large eroded arteries in ulcer base. A multicenter randomized controlled trial that compares OTSC to standard endoscopic treatment in the endoscopic treatment of refractory bleeding lesions has just been completed. The use of OTSC has been shown to be superior in achieving hemostatic control and reducing further bleeding. In this proposed randomized controlled trial, we would test the hypothesis that the use of OTSC, when used as the first or primary treatment, is superior to standard treatment in achieving hemostasis and thereby improve patients' outcomes.
Detailed Description
Endoscopic therapy has improved outcomes to patients with acute non-variceal upper gastrointestinal bleeding. Acid suppression therapy as an adjunct to endoscopic therapy further reduces recurrent bleeding and interventions. There remains a small subgroup of patients who continue to bleed or re-bleed after initial endoscopic hemostasis. These patients are often elderly with significant comorbid illnesses. In the 2007 National United Kingdom Audit, mortality was 30% in those after salvage surgery for refractory bleeding [1]. The current standard in endoscopic treatment is the use of either hemo-clips or thermal coagulation with or without pre-injection with diluted adrenaline. The two modalities are similar in their efficacies [2]. Their use is associated with a small but significant failure rate. Anatomically, the failed cases are usually larger deep ulcers with erosion into thick subserosal arteries [3]. In an ex vivo model, control of bleeding becomes inconsistent in arteries > 2mm in diameter in size with 3.2 mm contact thermal devices [4]. The investigators have few reports on in vivo data. Using thin barium angiography in 27 gastrectomy specimens from patients who underwent surgery for control of bleeding from their gastric ulcers, Swain and colleagues found vessels of varying sizes and disposition [5]. It was felt that artery beyond 1 mm would be difficult to control during endoscopy in a clinical setting. In a series of fatal deaths from bleeding gastroduodenal ulcers from Hong Kong [6], these arteries were around 3 mm in diameter at post-mortem examination. Over-the-scope clips or the Bear Claws were developed for the purpose of closure of GI luminal defects created at Natural orifice trans-luminal surgery. In clinical practice, OTSC are widely used for closure of GI perforations and anastomotic dehiscence. There have been anecdotal reports over the use of OTSC in the control of refractory bleeding from peptic ulcers [7, 8]. The investigators reported our experience in 9 such patients with successful hemostasis in all of them [9]. Further bleeding occurred in 2 patients. The investigators subsequently illustrated its use in difficult ulcers that failed standard endoscopic treatments; one of them showed a pseudo-aneurysm to a branch of the gastro-duodenal artery [10]. In our hospital, indication for OTSC use has been failure with conventional endoscopic treatments. The OTSC have several advantages over existing treatments. First, tissue compression on the bleeding artery is critical in control of bleeding. OTSC captures tissue size to that of an endoscope at least 9 mm in diameter. In theory, OTSC can compress arteries of significant size, beyond what can be achieved with standard treatment. Second, clip retention rate with OTSC is extremely and recurrent bleeding from clip loss or dislodgement can be avoided. Third, local complication from their applications is negligible. As a comparison, contact thermal coagulation carries a small risk (around 1%) of perforation. Investigator group has participated in a multicenter randomized trial [11] that compares OTSC to standard therapies in endoscopic management of refractory non-variceal bleeders. OTSC has been shown to be superior in the control of bleeding (30/33 patients, 91% vs. 15/26 patients 57.6%, P=0.005) and is associated with fewer re-bleeding after hemostasis 6/33, 18% vs. 10/26, 38%, P=0.14). In the current proposed randomized controlled trial, the investigators compare OTSC and standard therapies (hemo-clipping or thermal coagulation) as the primary endoscopic treatment in the control of bleeding from non-variceal causes in patients who present with acute upper gastrointestinal bleeding. The investigators argue that OTSC should be used as the first treatment given its promise in better bleeding control over other treatment methods. Rebleeding patients are exposed to excessive risks in organ failure and death. Furthermore, management of recurrent bleeding is expensive e.g. cost of angiographic embolization, surgery and intensive care stay. Investigators hypothesize that OTSC as the first treatment during index endoscopy is superior to standard endoscopic therapy in the overall rate of hemostasis. Knowledge from this clinical trial will enable us to choose the correct treatment for bleeding lesions. Research plan and methodology Trial Design - A randomized controlled trial The trial will be executed in accordance with Good Clinical Practice guidelines Randomization - Patients with overt signs of acute upper GIB (melena, hematemesis, drop in haemoglobin with or without hypotension) are invited to participate in the trial. Investigators or research nurses approach patients and obtain their written consents. During endoscopy, if they have bleeding lesions suitable for standard endoscopic treatment and OTSC, the endoscopist then requests the next number sealed envelope to be opened by an endoscopy nurse. Patients are randomized to receive either standard endoscopic treatment (contact thermal methods or hemoclips with or without pre injection with diluted epinephrine), or the use of OTSC. Indications for endoscopic treatment are active bleeding (pulsatile or Forrest Ia bleeding, oozing from a visible vessel or a protuberance otherwise referred to as Forrest I b bleeding, or a non bleeding visible vessel or Forrest IIa lesion). Clots overlying bleeding lesions are irrigated or elevated using a cheese wiring technique with a minisnare. If a vessel is unveiled, randomization can then proceed and the assigned treatment is then carried out. The random number list is generated by computer software. Blinding - no blinding Participants - Consecutive patients admitted with overt signs of acute upper GIB (melena, hematemesis, drop in hemoglobin with or without hypotension) and documented bleeding (Forrest I) from a non-variceal upper gastrointestinal sourcegastro-duodenal ulcers, Mallory Weiss tear, cancers, Dieulafoy's and other vascular lesions) at endoscopy. Interventions - Patients are randomly assigned at endoscopy to receive; Patients are randomized in a 1:1 ratio to receive; endoscopic treatment using OTSC or standard therapies. No cross over to treatment of the other arm is allowed. A full description of the bleeding lesion and the success of endoscopic therapy are provided and documented in the electronic endoscopy report. It is unrealistic and impossible to completely blind ward staff as a plain abdomen x-ray will readily an OTSC or indeed most hemo-clips. After successful endoscopy, patients are started on an intravenous infusion with proton pump inhibitor (PPI) for 72 hours. Thereafter, patients go onto receive an oral PPI or standard PPI H. pylori eradication therapy should the patient is infected. It is generally recommended that patients be transfused to a hemoglobin level of around 7 or 8 g/dl. In patients with significant cardiac co-morbidities, a higher transfusion threshold is allowed. The management of antiplatelet agents and anticoagulation in these patients is based on ASGE guidelines. Further bleeding is defined by failure to control bleeding during first endoscopy or recurrent bleeding after initial control. Recurrent bleeding is defined by fresh hematemesis, fresh melena or hematochezia with hemodynamic instability (systolic blood pressure lower than 90mmHg, heart rate greater than 110 per minute) and/or drop in hemoglobin > 2g/dl in 24 hours after transfusion to around 8 g/dl. An episode of recurrent bleeding has to be confirmed by repeat endoscopy showing fresh blood in stomach or active bleeding from the previously treated lesion. Statistics analysis An independent data monitoring and safety panel will be formed by senior physicians from our Clinical Trial Centre at the Chinese University of Hong Kong to adjudicate over the occurrence of primary outcome events. Analyses are by intention-to-treat and then per protocol principles. The primary outcome between groups over 30 days is compared using a time-to-event type analysis with a log rank test. An adjusted analysis or Cox regression model will be used in the presence of significant difference in the baseline covariates. Initial rate of hemostasis and recurrent bleeding within 30 days are independently reported and compared using a chi-square test. Categorical data in secondary outcome measures are compared between groups again using chi-square test. Parametric and non-parametric data are compared using student's t test and Mann-Whitney U test respectively.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Upper Gastrointestinal Bleeding, Tumor Bleeding

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Patients are randomized in a 1:1 ratio to receive; endoscopic treatment using OTSC or standard therapies Stratified randomization according to size of ulcers and non-ulcer lesions size smaller than10mm in diameter size equal to 10mm and less than 20mm in diameter size equal or greater than 20mm in diameter non-ulcer lesions
Masking
None (Open Label)
Allocation
Randomized
Enrollment
191 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Over-the-scope Clips
Arm Type
Experimental
Arm Description
Endoscopic Application of Over-the-scope Clips
Arm Title
standard treatment
Arm Type
Active Comparator
Arm Description
standard treatment of either hemo-clipping or thermo-coagulation with or without pre injection with diluted epinephrine <=20 clips or pulse
Intervention Type
Device
Intervention Name(s)
Over-the-scope Clips
Other Intervention Name(s)
OTSC
Intervention Description
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 tissue.
Intervention Type
Device
Intervention Name(s)
Hemo-clipping
Other Intervention Name(s)
quick clips
Intervention Description
Hemo-clipping <=20 clips
Intervention Type
Device
Intervention Name(s)
thermo-coagulation
Other Intervention Name(s)
contact thermo-coagulation
Intervention Description
contact thermo-coagulation < = 8 pulses
Intervention Type
Drug
Intervention Name(s)
Epinephrine
Other Intervention Name(s)
adrenaline
Intervention Description
epinephrine injection (diluted 1:1000) beneath peptic ulcer <20 mls
Primary Outcome Measure Information:
Title
Bleeding free probability in 30 days after randomization
Description
Further bleeding is defined by failure to control bleeding during first endoscopy or recurrent bleeding after initial control.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
re-interventions in the form of endoscopic
Description
heater probe or clips endoscpic therapy
Time Frame
30 days
Title
angiographic treatment
Description
angiopgram with embolization to bleeding vessel
Time Frame
30 days
Title
surgical treatment
Description
surgical treatment if primary failure or rebleeding
Time Frame
30 days
Title
blood transfusion 4. blood transfusion blood transfusion
Description
amount of total blood transfusion
Time Frame
30 days
Title
adverse events
Description
adverse events (related or unrelated to endoscopic treatment)
Time Frame
30 days
Title
mortality
Description
deaths from all causes
Time Frame
30 days
Title
cost analysis (Based on the cost data from the Hospital
Description
Authority Gazette, Hong Kong Special Administrative Region Government; the investigator will calculate cost to avert one episode of further clinical bleeding with the use of OTSC or standard treatment. A series of sensitivity analyses varying device costs and over a range of re-bleeding rates.)
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
111 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with overt signs of acute upper GIB (melena, hematemesis, drop in hemoglobin with or without hypotension) documented bleeding lesions suitable for standard endoscopic treatment during endoscopy Exclusion Criteria: without a full informed consent from the patient or his legally-acceptable representatives Age <18 years Pregnant Lactating women Moribund patients not considered for active treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James LAU, MD
Organizational Affiliation
CUHK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sunshine Hospital
City
Melbourne W.
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Facility Name
Footscray Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
Beijing Friendship Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
The First Affliated Hospital of SooChow University
City
Suzhou
State/Province
Jiangsu
Country
China
Facility Name
The First Affliated Hospital, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
Facility Name
Ningbo First Hospital
City
Ningbo
State/Province
Zhejiang
Country
China
Facility Name
Endoscopy Centre, Prince of Wales Hospital
City
Hong Kong
State/Province
N.t.
Country
Hong Kong
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21490373
Citation
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Results Reference
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PubMed Identifier
17566018
Citation
Sung JJ, Tsoi KK, Lai LH, Wu JC, Lau JY. Endoscopic clipping versus injection and thermo-coagulation in the treatment of non-variceal upper gastrointestinal bleeding: a meta-analysis. Gut. 2007 Oct;56(10):1364-73. doi: 10.1136/gut.2007.123976. Epub 2007 Jun 12.
Results Reference
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PubMed Identifier
18684171
Citation
Elmunzer BJ, Young SD, Inadomi JM, Schoenfeld P, Laine L. Systematic review of the predictors of recurrent hemorrhage after endoscopic hemostatic therapy for bleeding peptic ulcers. Am J Gastroenterol. 2008 Oct;103(10):2625-32; quiz 2633. doi: 10.1111/j.1572-0241.2008.02070.x. Epub 2008 Aug 5.
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3493938
Citation
Johnston JH, Jensen DM, Auth D. Experimental comparison of endoscopic yttrium-aluminum-garnet laser, electrosurgery, and heater probe for canine gut arterial coagulation. Importance of compression and avoidance of erosion. Gastroenterology. 1987 May;92(5 Pt 1):1101-8. doi: 10.1016/s0016-5085(87)91065-1.
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PubMed Identifier
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Monkemuller K, Toshniwal J, Zabielski M, Vormbrock K, Neumann H. Utility of the "bear claw", or over-the-scope clip (OTSC) system, to provide endoscopic hemostasis for bleeding posterior duodenal ulcers. Endoscopy. 2012;44 Suppl 2 UCTN:E412-3. doi: 10.1055/s-0032-1325737. Epub 2012 Nov 20. No abstract available.
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Results Reference
derived

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Over-the-scope Clips and Standard Treatments in Endoscopic Control of Acute Bleeding From Non-variceal Upper GI Causes

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