Acute Upper Gastrointestinal Bleeding Clinical Trial
Official title:
Endoscopic Application of a Hemostatic Powder TC-325 Versus Standard Treatment in the Control of Acute Upper Gastrointestinal Bleeding From Nonvariceal Causes; A Non-inferiority Randomized Trial
Acute upper gastrointestinal bleeding is a common medical emergency. Bleeding peptic ulcers and other non-variceal causes constitute to about 95% of all cases of bleeding. Endoscopic treatment stops active bleeding, reduces rate of further bleeding and leads to improved patients outcomes. Endoscopic treatment can be technically demanding especially with lesions in difficult anatomic positions and to endoscopists with less experience. TC-325 is a propriety mineral blend hemostatic powder used to compress external civilian and military traumatic injuries. Investigators reported the first endoscopic application of TC-325 in 20 patients with actively bleeding gastro-duodenal ulcers. Investigators were able to stop bleeding in 19 of them. Subsequent case series from others reported a similar rate in the acute control of bleeding. To further define the role of TC-325 as a mono-therapy, a comparison to the current standard in endoscopic treatment is required. A non-inferiority randomized trial is being proposed to compare endoscopic use of TC-325 as a mono-therapy to current standards (i.e. hemoclips or thermo-coagulation with or without pre-injection with diluted epinephrine) in hemostatic treatment in patients with acute upper gastrointestinal bleeding from non-variceal causes. The non-inferiority primary endpoint is control of bleeding over 30 days from randomization. Other outcome endpoints include further endoscopic, angiographic or surgical treatments, hospitalization, blood transfusion and mortality. Investigators also compare ease of therapy measured by procedure time and a 10 cm visual analogue scale rated by endoscopists. Endoscopic application of TC-325 is a simple and less skill dependent technique. It may prove useful in bleeding from anatomically challenging sites of the gastro-duodenal tract.
Impact and Objectives Long-term impact :Acute upper gastrointestinal bleeding is a common
medical emergency. The majority of causes are non-variceal in etiology and are mostly peptic
ulcers. Endoscopic treatment reduces further bleeding, surgery and deaths from the condition.
The current endoscopic treatment to non-variceal causes includes.the use of hemo-clips and
thermo-coagulation. Endoscopic treatment is skill demanding and can be challenging in
difficult access areas in the gastroduodenal tract e.g. posterior bulbar duodenum. Endoscopic
application of hemostatic powder (labeled TC-325) is technically easy. The proposed
randomized trial is the first to compare TC-325 to standard treatment. An non-inferior
treatment of hemostatic powder TC-325 would mean wider application of endoscopic treatment as
most endoscopists are able to use it. It can at least be used for acute control of bleeding
allowing time for more definitive treatment.
Objectives :
1. To compare clinical efficacy of the hemostatic powder TC-325 to standard treatment in
overall rate of hemostasis in patients with active bleeding from a non-variceal source
in the upper gastrointestinal tract. Investigators aim to determine the initial rate of
hemostasis and the rate of further bleeding after initial control in both groups.
Investigators would like to define role of TC-325 as a mono-therapy when compared to
standard treatment. The rate of further bleeding after initial control would also inform
us if endoscopic application of TC-325 should be followed by a second look endoscopy
with targeted treatment to the bleeding artery.
2. To compare ease of application of hemostatic powder TC-325 to standard treatment.
Background of Research, Research Plan and Methodology :
a. Background of research Acute upper gastrointestinal bleeding (AUGIB) is one of the
commonest medical emergencies. Mortality in patients with AUGIB remains high. In the National
United Kingdom Audit of 2007, the crude overall in patient mortality was 10%. Mortality
increases in patients with advanced age and significant comorbid illnesses. Endoscopic
therapy greatly improves outcomes in patients with AUGIB. In pooled analyses of randomized
controlled trials on endoscopic therapy in patients with nonvariceal upper gastrointestinal
bleeding, endoscopic therapy significantly reduces not only further bleeding but also surgery
and deaths.
The National United Kingdom audit in 2007 found continuing delays in endoscopy and treatment
in patients admitted with AUGIB. Only 55% of patients judged to belong to the high risk group
underwent endoscopy within 24 hours of their admissions, and only 74% of high risk lesions
were offered endoscopic treatment. The gap in service provision may be an organization issue.
The lack of skills in endoscopic therapy may also contribute to this shortfall. An
easy-to-use endoscopic treatment is likely to help generalize endoscopic hemostasis.
The current standard of endoscopic therapy consists of the use of hemoclips or
thermo-coagulation with or without pre-injection with diluted epinephrine. TC-325 is a
proprietary, inert inorganic mineral blend powder approved by FDA for the purpose of
hemostasis. In the United States the powder is used for compression treatment of bleeding
from external injuries in both civilian and combat casualties. The powder is highly
absorbent. When in contact with fluid or blood the powder rapidly concentrates clotting
factors at the bleeding site and forms an adherent coagulum. In 2011, Investigators reported
the first endoscopic human application of the hemostatic powder TC-325. In 20 patients with
Forrest type I bleeding from their gastro-duodenal ulcers, Investigators were able to control
bleeding in 19 of them. The single patient with refractory bleeding from an angular gastric
ulcer underwent angiography to his left gastric artery and a pseudo-aneurysm was found
arising from the article. The aneurysm was successfully embolized with coils by angiographic
methods. None of these patients needed surgery or died when followed up for 30 days. These
initial results were encouraging. In gastroduodenal ulcers with Forrest I bleeding, rate of
further bleeding would be around 55% if untreated by endoscopy.
Subsequent to this pilot study, several series were published on the endoscopic use of
TC-325. The pooled rate in the initial control of bleeding with the use of TC-325 was 89.6%.
Rate of further bleeding after hemostasis was 19.2%. The reported series consisted of
patients with different case-mix but exclusively non-variceal in etiologies. Indications for
use of TC-325 also varied in these series. The powder was used as mono-therapy, in
combination to other endoscopic therapies or as a rescue therapy when conventional endoscopic
treatment failed. In the absence of comparative studies, the role of TC-325 remains
undefined.
Herein Investigators propose a randomized controlled study to compare endoscopic use of
TC-325 as a mono-therapy to current standards of hemostasis using either hemo-clips or
contact thermo-coagulation with or without diluted epinephrine in patients with active
bleeding (Forrest type I) from non-variceal upper GI causes. Investigators hypothesize that
endoscopic application of TC-325 would not be inferior in the control of bleeding from
non-variceal sources when compared to standard treatment. If such is the case, endoscopic use
of TC-325 may be preferred over existing techniques because of simplicity in TC-325
application. It appeals especially to endoscopists with less experience in endoscopic
hemostasis. In lesions of challenging anatomical positions e.g. posterior bulbar duodenum,
TC-325 may prove superior.
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