To Compare a Hemostatic Powder TC-325 and Standard Treatment in the Control of Acute Upper Gastrointestinal Bleeding From Nonvariceal Causes
Condition: Acute Upper Gastrointestinal Bleeding
MeSH terms: Gastrointestinal Hemorrhage; Hemorrhage
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Endoscopic Application of a Hemostatic Powder TC-325; Hemo-clipping; Epinephrine; thermo-coagulation
Intervention type(s): Device; Device; Drug; Device
Intervention description(s): Endoscopic Application of a Hemostatic Powder TC-325 <=150g once; Hemo-clipping <=20 clips; epinephrine injection endoscopically <20 mls; contact thermo-coagulation < = 4 pulses
Other intervention name(s): quick clips; adrenaline; contact thermo-coagulation
Intervention MeSH terms: Epinephrine; Hemostatics
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment