To Compare a Hemostatic Powder TC-325 and Standard Treatment in the Control of Acute Upper Gastrointestinal Bleeding From Nonvariceal Causes
To Compare a Hemostatic Powder TC-325 and Standard Treatment in the Control of Acute Upper Gastrointestinal Bleeding From Nonvariceal Causes
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.
Inclusion Criteria:

 -  patients with overt signs of upper gastrointestinal bleeding (hematemesis, melena
 and/or circulatory instability)

 -  documented bleeding (Forrest I) from a non-variceal upper gastrointestinal source
 (gastro-duodenal ulcers, Mallory Weiss tear, cancers, Dieulafoy's and other vascular
 lesions) at endoscopy.

 Exclusion Criteria:

 -  without a full informed consent from the patient or his next of kin

 -  Age <18 years

 -  Pregnant

 -  Lactating women