An Observer Blinded Comparison of MACE and Conventional Upper Gastrointestinal Endoscopy in Upper GI Bleeding
An Observer Blinded Comparison of MACE and Conventional Upper Gastrointestinal Endoscopy in Upper GI Bleeding
Gastroscopy (OGD) is a useful test for investigating a variety of suspected upper GI
 disorders. But it is uncomfortable for patients and incurs the risk of intubation and
 sedation, plus a large proportion of procedures reveal insignificant or no pathology. Capsule
 endoscopy (CE) is the investigation of choice for diseases of the small bowel. It is safe,
 non-invasive and well-tolerated. The use of CE is traditionally restricted to the small
 bowel, although newer capsules to image the oesophagus and colon are currently in use.
 Previous capsules have failed to adequately image the stomach due to its' large volume and
 rugal folds. Recently a magnetic capsule and handheld magnet has been developed (Mirocam
 Navi, Intromedic Ltd, Seoul, Korea) to enable an element of manoeuvrability of the capsule.
 This is unnecessary in the small bowel where the capsule is propelled along its' tubular
 structure by peristalsis, but in the capacious stomach this may allow the capsule to be
 steered to examine all areas of the stomach. We have already conducted two feasibility
 studies in porcine models with promising results and a trial has already evaluated the
 equipment to steer the small bowel capsule through the stomach into the duodenum. An ongoing
 study is comparing the ability of this technique to examine the stomach against conventional
 OGD, in patients with recurrent iron deficiency anaemia. The next stop would be to compare
 the two modalities under other different conditions.

 We wish to undertake a prospective single blind controlled trial comparing magnetically
 assisted capsule examination to conventional OGD in diagnosing upper gastrointestinal
 pathology in patients with gastrointestinal bleeding.
Intubational endoscopy is uncomfortable for patients and incurs the risks of bleeding,
 perforation and sedation related complications. Gastroscopy is the 'gold-standard'
 investigation to identify upper gastrointestinal pathology but is poorly tolerated by
 patients. Moreover a large proportion of gastroscopies are normal or reveal insignificant
 pathology and despite efforts to produce pre-procedure scoring systems to grade the
 appropriateness of the procedure, correlation with diagnostic yield is poor. Capsule
 endoscopy is very well tolerated but is traditionally reserved for examination of the small
 bowel since it cannot be manipulated to view all areas of the capacious stomach. A capsule
 which could overcome this and be steered to examine all areas of the mucosal surface of the
 stomach as an alternative to intubational endoscopy would be advantageous to patients.
 Mirocam Navi (MC1000-WM, Intromedic Ltd, Seoul, Korea) is a small bowel capsule endoscope
 with an inclusion of magnetic material. Available accessories include a handheld magnet with
 which to gain some control over the capsule in the upper gastrointestinal tract. The capsule
 is CE marked (CE0120) with the handheld magnet classed as an accessory. In order to assess
 the feasibility of our hypothesis we conducted a study in an ex vivo porcine stomach model,
 commonly used for endoscopy training purposes. Different coloured/shaped beads were sewn into
 each major location of the stomach (cardia, fundus, greater and lesser curve, anterior and
 posterior wall, antrum and D1). The stomach was distended with 1000mls of water. Endoscopy
 was performed according to a set protocol. All stomach tags were identified in 87.2% (41/47)
 of examinations.

 This was followed by a double blind, randomised controlled trial comparing magnetically
 assisted capsule endoscopy (MACE) with conventional upper gastrointestinal endoscopy to
 detect coloured beads in a porcine stomach model. Gastroscopy correctly identified 88%
 (79/90) beads, MACE correctly identified 89% (80/90) beads and thus is noninferior to
 gastroscopy in this setting (95% CI 82.76%-95.24%). Mean examination times for gastroscopy
 and MACE were 3.34 minutes and 9.90 minutes respectively. Clearly there are significant
 differences between a porcine model and live human stomach. However, these studies provide
 proof of the principle that a small bowel capsule endoscope can be manipulated to make
 targeted movements within the stomach. We now also have one completed human trial assessing
 whether the magnetic controller can be utilised to manipulate the small bowel capsule through
 the stomach into the duodenum to improve the completion rate of small bowel capsule
 examinations. Another trial is also near completion comparing the diagnostic ability ,within
 the stomach, of MACE compared to conventional gastroscopy in the context of recurrent iron
 deficiency anaemia.

 In order to develop the protocol for our study, discussions were made with other health
 professionals (consultants, specialist nurses and ward nurses) who are involved in performing
 or reporting gastroscopy and small bowel capsule endoscopy examinations outside of the
 research team. Feedback was used to modify the study protocol so it could be as patient and
 user friendly as possible without compromising the overall aim to answer the research
 question.

 Additionally the protocol has been externally peer reviewed and subsequent modifications
 made.

 From our porcine and two human trials it is clear that to obtain reasonable views of the
 stomach to be able to guide the capsule the stomach needs to be distended. In our porcine
 study we achieved good results with 1000mls of water. We felt that this would be an
 acceptable amount for a patient to drink prior to magnetically assisted capsule endoscopy,
 and the two human trials we have completed to date have proven excellent tolerance to this
 volume of water.

 RECRUITMENT Patients will be offered information about the trial at the time of their initial
 clinical encounter in the outpatient clinic. Written information is provided at this stage
 and will be followed by confirmation of consent on the day of, but prior to, the procedure.
 The research team will be available when the patient attends for their procedures to answer
 any questions or concerns. Additionally a contact telephone number for the research team is
 provided on the patient information sheet for any other concerns or queries.

 INCLUSION/EXCLUSION We have made every effort to enable the study to be open to a wide range
 of patients however we have currently limited the study to patients with upper
 gastrointestinal bleeding to allow the highest possibility for pathology detection for either
 endoscopic modality and hence facilitate comparison of diagnostic ability. Specific
 considerations have been made to ensure that patients will be excluded from the study if
 there is to be any delay/interference to the standard management of upper gastroinstinal
 bleeding.

 CONSENT All participants will be consented as per the study consent form. All members of the
 research team are formally trained in consent procedures and assessment of capacity. Any
 participant without capacity to consent will not be included in the trial. The principal
 investigator is trained in the ethical principles underpinning informed consent and is bound
 to these principles as part of good medical practice.

 RISKS/BURDENS/BENEFITS The participant is subject to the risk of the procedures of
 gastroscopy and small bowel capsule endoscopy itself. Bleeding and perforation are the major
 risks of undergoing a gastroscopy and occur in 0.02% of procedures. There is also a risk of
 sedation related complications if the patient chooses this option. The main risk of SBCE is
 retention of the capsule, occurring in up to 2% of examinations. Since the participant is
 undergoing these procedures as part of their medical investigation these risks are discussed
 when the patient is offered the investigations at the time of booking, they are also formally
 consented by a trained individual when they attend for the procedure. Participants are not
 felt to be at any additional risk by undergoing magnetically steerable capsule examination of
 the stomach.
Inclusion Criteria:

 -  Patients aged 18 years and over

 -  Patients presenting with haematemesis (fresh blood or coffee grounds) and/or malaena
 within the previous 48 hours, who require a gastroscopy as part of their diagnostic
 investigations

 Exclusion Criteria:

 -  Patients under the age of 18 years or over the age of 80 years.

 -  Patients who have a suspected UGIB and haemodynamic instability, i.e. hypotension
 (systolic blood pressure <100mmHg) and tachycardia (>100 bpm), requiring urgent
 resuscitation

 -  Pre-endoscopy Rockall score >4 (patients with a lower pre-endoscopy Rockall score but
 haemodynamically unstable will still be excluded)

 -  Active vomiting or haematemesis

 -  Patients with a permanent pacemaker, implantable cardioverter-defibrillator or REVEAL
 device

 -  Patients with any electronic/magnetic/mechanically controlled devices e.g. sacral
 nerve stimulators, bladder stimulators

 -  Patients with dysphagia, odynophagia or known swallowing disorder

 -  Patients with known Zenker's diverticulum

 -  Patients with suspected bowel obstruction or bowel perforation

 -  Patients with prior bowel obstruction

 -  Patients with gastroparesis or known gastric outlet obstruction

 -  Patients with known Crohn's disease

 -  Patients with a history of GI tract surgery (Billroth I, Billroth II, Oesophagectomy,
 gastrectomy or bariatric procedure)

 -  Patients that are pregnant or lactating

 -  Patients with altered mental status that would limit their ability to swallow

 -  Patients with allergy to conscious sedation or metoclopramide

 -  Patients unwilling to swallow the capsule

 -  Patients unwilling to undergo a possible abdominal XR if suspected capsule retention
 occurs

 -  Patients with known dementia affecting ability to consent

 -  Patients who are unable to understand or speak English

 -  Patients unable to provide written informed consent