Over-the-scope Clips and Standard Treatments in Endoscopic Control of of Acute Bleeding From Non-variceal Upper GI Causes(OTSC Study)

Endoscopic therapy has improved outcomes to patients with acute non-variceal upper gastrointestinal bleeding. Acid suppression therapy as an adjunct to endoscopic therapy further reduces recurrent bleeding and interventions. There remains a small subgroup of patients who continue to bleed or re-bleed after initial endoscopic hemostasis. These patients are often elderly with significant comorbid illnesses. In the 2007 National United Kingdom Audit, mortality was 30% in those after salvage surgery for refractory bleeding [1]. The current standard in endoscopic treatment is the use of either hemo-clips or thermal coagulation with or without pre-injection with diluted adrenaline. The two modalities are similar in their efficacies [2]. Their use is associated with a small but significant failure rate. Anatomically, the failed cases are usually larger deep ulcers with erosion into thick subserosal arteries [3]. In an ex vivo model, control of bleeding becomes inconsistent in arteries > 2mm in diameter in size with 3.2 mm contact thermal devices [4]. The investigators have few reports on in vivo data. Using thin barium angiography in 27 gastrectomy specimens from patients who underwent surgery for control of bleeding from their gastric ulcers, Swain and colleagues found vessels of varying sizes and disposition [5]. It was felt that artery beyond 1 mm would be difficult to control during endoscopy in a clinical setting. In a series of fatal deaths from bleeding gastroduodenal ulcers from Hong Kong [6], these arteries were around 3 mm in diameter at post-mortem examination.

Over-the-scope clips or the Bear Claws were developed for the purpose of closure of GI luminal defects created at Natural orifice trans-luminal surgery. In clinical practice, OTSC are widely used for closure of GI perforations and anastomotic dehiscence. There have been anecdotal reports over the use of OTSC in the control of refractory bleeding from peptic ulcers [7, 8]. The investigators reported our experience in 9 such patients with successful hemostasis in all of them [9]. Further bleeding occurred in 2 patients. The investigators subsequently illustrated its use in difficult ulcers that failed standard endoscopic treatments; one of them showed a pseudo-aneurysm to a branch of the gastro-duodenal artery [10]. In our hospital, indication for OTSC use has been failure with conventional endoscopic treatments.

The OTSC have several advantages over existing treatments. First, tissue compression on the bleeding artery is critical in control of bleeding. OTSC captures tissue size to that of an endoscope at least 9 mm in diameter. In theory, OTSC can compress arteries of significant size, beyond what can be achieved with standard treatment. Second, clip retention rate with OTSC is extremely and recurrent bleeding from clip loss or dislodgement can be avoided. Third, local complication from their applications is negligible. As a comparison, contact thermal coagulation carries a small risk (around 1%) of perforation.

Investigator group has participated in a multicenter randomized trial [11] that compares OTSC to standard therapies in endoscopic management of refractory non-variceal bleeders. OTSC has been shown to be superior in the control of bleeding (30/33 patients, 91% vs. 15/26 patients 57.6%, P=0.005) and is associated with fewer re-bleeding after hemostasis 6/33, 18% vs. 10/26, 38%, P=0.14).

In the current proposed randomized controlled trial, the investigators compare OTSC and standard therapies (hemo-clipping or thermal coagulation) as the primary endoscopic treatment in the control of bleeding from non-variceal causes in patients who present with acute upper gastrointestinal bleeding. The investigators argue that OTSC should be used as the first treatment given its promise in better bleeding control over other treatment methods. Rebleeding patients are exposed to excessive risks in organ failure and death. Furthermore, management of recurrent bleeding is expensive e.g. cost of angiographic embolization, surgery and intensive care stay.