Clinical trial NCT06188585: Randomized Trial of UI-EWD vs. Conventional Endoscopic Therapy for Bleeding Ulcers
Official title: Randomized Controlled Multi-Center Non-Inferiority Trial of UI-EWD (Nexpowder™) vs. Conventional Treatment as First-Line Endoscopic Therapy for Patients With High-Risk Bleeding Ulcers (TREET)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Gastrointestinal Bleeding
Keywords: Gastrointestinal hemorrhage
Peptic Ulcer
Lead sponsor: Medtronic - MITG
Sponsor class: INDUSTRY
Collaborators: name: North American Science Associates Ltd.
First posted: 2024-01-03
Enrollment: 278
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are randomly assigned with concealed allocation in a 1:1 ratio to receive treatment with UI-EWD hemostatic powder (Nexpowder) or conventional endoscopic hemostatic therapy (defined as bipolar electrocoagulation or clips with or without epinephrine injection therapy).
Primary purpose: TREATMENT

Brief summary: A prospective, multi-center, noninferiority randomized controlled trial designed to compare the efficacy of UI-EWD (Nexpowder™) hemostatic powder versus conventional endoscopic hemostatic therapy in patients presenting with acute overt gastrointestinal bleeding which is found at endoscopy to be due to a gastric or duodenal ulcer with active bleeding (spurting or oozing) or a non-bleeding visible vessel.

Detailed description: Endoscopic hemostatic therapy is recommended as the first line therapy for patients with upper gastrointestinal bleeding (UGIB) due to ulcers with active bleeding or a non-bleeding visible vessel identified at endoscopy. A variety of endoscopic modalities are used in the treatment of UGIB, including thermal therapies (e.g., bipolar electrocoagulation), injection therapy (e.g., epinephrine), clips, and hemostatic powder spray. Topical therapies, such as hemostatic powder spray, have been the most recent addition to the armamentarium of endoscopic therapies for UGIB.

UI-EWD hemostatic powder (Nexpowder™), which is manufactured by NextBiomedical and distributed by Medtronic, is approved for treatment of nonvariceal UGIB in the U.S., Canada, European Union and other countries.

A retrospective study of UI-EWD hemostatic powder in 56 patients with active bleeding found immediate hemostasis in 54 (96.4%), with rebleeding within 7 days in only 2 patients (3.7%)\[1\]. A large multi-center randomized trial in 340 patients with nonvariceal UGIB and either active bleeding or a non-bleeding visible vessel compared conventional endoscopic hemostatic therapy alone to conventional therapy plus UI-EWD. Rebleeding was significantly lower in the UI-EWD group at 3 days (3 vs. 11%) and at 30 days (19% vs. 7%) \[2\].

The primary aim of this trial is to demonstrate that UI-EWD when used as initial hemostatic therapy is non-inferior to older conventional endoscopic hemostatic therapy for the treatment of patients with high-risk peptic ulcer bleeding.

Eligibility criteria: Inclusion Criteria:

1. Adults age 22 years or older
2. Presentation with acute overt gastrointestinal bleeding (hematemesis, melena, and/or hematochezia)
3. Subject voluntarily agrees to participate in the clinical investigation, provides written informed consent, and will be able to comply with the investigational protocol in the opinion of the site investigator
4. Cause of bleeding as determined at endoscopy is gastric or duodenal ulcer bleeding with active spurting or oozing bleeding or a non-bleeding visible vessel. The definition of "active oozing" will require bleeding to persist for ≥ 3 minutes of endoscopic observation.

Exclusion Criteria:

1. Incarceration
2. Subjects that are not able to provide written informed consent
3. Subject already hospitalized for another condition when UGIB begins
4. Pregnancy or nursing mothers
5. Endoscopic hemostatic treatment in the past 30 days
6. Use of triple antithrombotic therapy at the time of presentation
7. Subjects who underwent gastric or duodenal endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) procedures within the past 2 months
8. Platelet count \< 50 x 10\^9/L
9. INR \> 3.5 (or prothrombin time \>35 seconds in patient not on warfarin and only prothrombin time is provided by local lab), at time of procedure or closest to procedure time
10. Subjects who have documented galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
11. Subjects with documented hypersensitivity to Brilliant Blue FCF
12. Subjects with suspected bowel obstruction or gastrointestinal fistulas, and those suspected or are at high risk of having gastrointestinal perforation.
13. Endoscopy not performed within 30 hours of presentation

Primary outcomes:
measure: No further bleeding during the 7-day period after hemostatic treatment
timeFrame: 7 days
Secondary outcomes:
measure: Composite 30-day outcome of further bleeding
timeFrame: 30 days
measure: Number of participants with active bleeding (Forrest 1a/1b) at randomization who have initial hemostasis with study-assigned endoscopic therapy
timeFrame: During index endoscopy procedure
measure: Number of participants with recurrent bleeding over the 7-day period after randomization
timeFrame: 7 days
measure: Mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: New Haven
country: United States
facility: Yale
state: Connecticut
city: Chicago
country: United States
facility: RUSH University
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Piscataway
country: United States
facility: Rutgers University
state: New Jersey
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: NYU Langone
state: New York
city: Montréal
country: Canada
facility: McGill University
state: Quebec
city: Toronto
country: Canada
facility: St. Michael's Hospital
city: Vancouver
country: Canada
facility: Vancouver General Hospital
city: Hvidovre
country: Denmark
facility: Copenhagen University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Paris
country: France
facility: St. Antoine
city: Afula
country: Israel
facility: Emek Medical Center
city: London
country: United Kingdom
facility: Cleveland Clinic London
Study officials:
affiliation: Yale University
name: Loren Laine, MD
role: STUDY_CHAIR
References:
citation: Park JS, Kim HK, Shin YW, Kwon KS, Lee DH. Novel hemostatic adhesive powder for nonvariceal upper gastrointestinal bleeding. Endosc Int Open. 2019 Dec;7(12):E1763-E1767. doi: 10.1055/a-0982-3194. Epub 2019 Dec 10.
citation: Cha B. A Randomized Control Study Evaluating the Efficacy of a Hemostatic Powder (UI-EWD) in Decreasing the Rate of Upper Gastrointestinal Re-Bleeding in Patients Treated with Endoscopic Therapy for High-Risk Lesions. Oral presentation presented at: Digestive Disease Week 2023; May 9, 2023; Chicago, IL.