TC-325 (HEMOSPRAY™) VS. CURRENT STANDARD OF CARE IN MANAGING MALIGNANT GASTROINTESTINAL BLEEDING: A PILOT STUDY TO INFORM A RANDOMIZED CONTROLLED TRIAL.

Study Overview
=================
Brief Summary
-----------------
Introduction: Gastrointestinal (GI) bleeding arising from malignant tumors is increasingly recognized as a result of oncological advances and improved detection methods, and stems from local vessel damage and tumor invasion with associated derangements in the hemostatic system(1, 2). Although conventional endoscopic hemostasis methods improve outcomes in UGIB due to peptic ulcers and other non-variceal benign bleeding lesions of the upper, and perhaps the lower GI tract, data on their use in hemorrhagic, upper or lower gastrointestinal neoplasms are scarce and associated with varying success in initial hemostasis and high rebleeding rates(3-7). Other recognized single or multimodality treatment approaches include radiation therapy, interventional angiography, and surgery. All exhibit disappointing rebleeding rates, and in the case of emergency surgery, high mortality(4, 8-11). Challenges associated with bleeding tumors include hematological derangements such as thrombocytopenia, disseminated intravascular coagulation, and neutropenia, as well as the endoscopic manipulation of friable, diffusely bleeding surfaces when attempting hemostasis(2, 12, 13). The recent advent of TC-325 (HemosprayTM) to Canada, Europe and Asia - referred henceforth as TC-325 - may provide a highly adapted novel endoscopic hemostatic therapeutic alternative for this refractory clinical entity, with promising uncontrolled observations having just been published by our group(13) and others(14). More robust controlled evaluative data are now needed. We propose to study the use of TC-325 in upper and lower malignant GI bleeding compared to contemporary standard of care, and more specifically seeks funding for a pilot study to inform a subsequent peer-review application for a larger, more definitive randomized clinical trial (RCT).

Conditions
-----------------
MALIGNANT GASTROINTESTINAL BLEEDING

Intervention / Treatment
-----------------
* Drug: TC-325 monotherapy on initial endoscopy ± radiation therapy, angioembolization, and/or surgery.
* Other: Current standard therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years or older able to comprehend the trial and provide written informed consent in French or English, or a close relative with power of attorney Patients who present with an upper or lower GI bleeding with a known luminal GI malignancy diagnosed within the past two years will be considered for enrolment. Endoscopic confirmation of an active GI bleed arising from a malignant tumor will be required for final inclusion Rebleeding in patients who presented with acute GIB with initial endoscopy suggesting a malignant source based on endoscopic appearance who have not been treated previously with TC-325 will also be included Exclusion Criteria: Refused by patient Pregnancy Bleeding from non-malignant GI sources such as gastritis/duodenitis, Mallory Weiss syndrome, peptic ulcer disease, varices, vascular malformations, radiation proctitis, polyps, hemorrhoids, and diverticulosis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control group<br>Current standard endoscopic therapy such as epinephrine injection, sclerotherapy, mechanical (endoclip). contact electrocautery/thermal, and non-contact electrocalcautery (APC) ± radiation therapy, angioembolization, and/or surgery. | Other: Current standard therapy<br> <br> * Other names: surgery;|
| Active Comparator: TC-325<br>TC-325 monotherapy on initial endoscopy ± radiation therapy, angioembolization, and/or surgery. | Drug: TC-325 monotherapy on initial endoscopy ± radiation therapy, angioembolization, and/or surgery.<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemostasis | The main outcome will be rate of immediate hemostasis with application of TC-325 or conventional hemostatic therapy. Immediate hemostasis is defined as the absence of bleeding following 3 minutes of observation after endoscopic therapy. | 3 minutes after endoscopic therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rebleeding | Rebleeding following randomization | 1, 3, 30, 90 and 180 days following randomization | 
| Transfusion | transfusion requirements | 30 days after randomization | 
| length of ICU admission | need for admission to and length of stay in a monitored care unit | 180 days | 
| Length of hospitalization | Total length of hospitalization | 180 days | 
| Complications | Complications associated with endoscopy | day 1 | 
| Additional treatment modalities | Rates of use of additional treatment modalities to stop persistent bleeding or rebleeding after the index event | 30 days | 
| Mortality |  | 180 days |