Capsule Endoscopy Versus Conservative Therapy for Obscure Gastrointestinal Bleeding

This study is a single center prospective randomized control trial comparing the utility of performing capsule endoscopy compared to conservative management with oral iron therapy as the initial course of action in patients with non-severe obscure occult or obscure overt gastrointestinal (GI) bleeding. The investigators hypothesize that outcomes in patients with non-severe obscure GI bleeding who receive conservative therapy with oral iron will not differ to those on oral iron who undergo capsule endoscopy.

Study Overview

• Status: Withdrawn
• Conditions: Hemorrhage; Anemia
• Intervention / Treatment: Dietary supplement: Ferrous sulfate; Device: Capsule Endoscopy

Detailed Description

Although the American Gastroenterological Association suggests that patients with obscure GI bleeding undergo a capsule endoscopy after a negative esophagogastroduodenoscopy (EGD) and colonoscopy, current recommendations from the British Society of Gastroenterology argue that unless there is an inadequate response to iron therapy, further imaging of the small bowel is probably not necessary. Several studies have demonstrated that this approach is reasonably safe. Furthermore, Laine et al demonstrated that when patients with obscure GI bleeding were randomized to either capsule endoscopy or dedicated small bowel contrast radiography, the rates of further bleeding, measured by subsequent hospitalization and blood transfusion events, were similar between the two groups. No study has randomized patients with obscure GI bleeding to receive capsule endoscopy vs. conservative therapy with oral iron.

This study is a single center prospective randomized control trial comparing the utility of performing capsule endoscopy compared to conservative management with oral iron therapy as the initial course of action in patients with non-severe obscure occult or obscure overt gastrointestinal bleeding. All patients will be recruited in the G.I. clinic, the endoscopy unit, or during inpatient consults after negative upper endoscopy and colonoscopy. The study will be explained to patients who qualify at that time. During this visit, patients will be questioned with regard to lower or upper G.I. symptoms, including abdominal pain, dyspepsia, nausea, vomiting, weight loss, diarrhea, change in stool character, melena and intermittent hematochezia. All patients will be started on standard dose oral iron therapy after informed consent. If the patient is already taking iron supplements, their dose with be adjusted to the standard regimen after informed consent. Patients will then be randomized to undergo capsule endoscopy or not. For patients randomized to undergo capsule endoscopy, all subsequent evaluation and treatment will be determined by capsule findings (i.e. capsule directed management) and standard of care at our institution.

Patients will be followed for 1 year. Follow up lab draws will occur at 1, 3, 6 and 12 months. They will consist of a complete blood count (CBC) and ferritin and can be performed at either the Medical University of South Carolina (MUSC) or an outside facility or office. If performed outside of MUSC, a standard medical records release form will be utilized to obtain the lab information. Patients will be provided with a paper card indicating their date of enrollment in the study. This card will be kept by the patient for the entire 12 month follow up period and will be collected at the end of the follow up period. The card will have an area where the patient can write the date of their first blood transfusion after enrollment. There will also be numerical checkboxes that the patient will check off for each unit of packed red blood cells (RBCs) they receive during the 12 month follow up period. Telephone calls will be made to each patient every 3 months after enrollment to inquire about hospitalizations and bleeding related procedures (including endoscopy, capsule, small bowel radiology, interventional radiology and surgery). Records of these hospitalizations and procedures will be obtained using a standard medical records release form.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult men and post-menopausal women with iron deficiency anemia and pre-menopausal women with iron deficiency anemia and a negative gynecologic workup or adults with overt GI bleeding as defined by melena or hematochezia with a ≥2 gram drop in hemoglobin after stabilization (Iron deficiency is defined as hemoglobin <13.7 g/dL in men and <12 g/dL in women with serum ferritin level <50 ng/mL). Also, patients with an otherwise unexplained drop in hemoglobin of ≥ 2 g/dL in the setting of hemoccult positive stool
• Negative EGD and colonoscopy for source of GI bleeding within six months of enrollment into the study.

Exclusion Criteria:

• Ongoing overt gastrointestinal bleeding requiring ≥4 units of packed RBC's on any given day in the setting of overt bleeding, blood transfusions on separate days (separated by ≥12 hours), or ≥6 units of packed RBC's over the previous 7-day period prior to presentation, in the setting of overt bleeding.
• Myocardial infarct, acute neurologic event, sepsis, or respiratory failure within the previous 1 week
• History of small bowel obstruction
• Pregnant women
• Prisoners
• Age less than 18
• Known GI or hematologic malignancy
• Achalasia
• Contraindications to capsule endoscopy (inability to take prep), or felt unsafe to undergo capsule as per study investigators
• Esophageal stricture that precludes even endoscopic capsule placement
• History of upper GI or small bowel surgery
• Inability to take oral iron.
• Active IV iron use.
• Alternate source of blood loss (e.g., menorrhagia)
• Hematemesis sufficient to be the cause of the hemoglobin decline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Oral Iron	Dietary supplement: Ferrous sulfate; Ferrous sulfate 325mg by mouth twice daily for the duration of the 12 month follow up period
Other: Oral Iron and Capsule Endoscopy	Dietary supplement: Ferrous sulfate; Ferrous sulfate 325mg by mouth twice daily for the duration of the 12 month follow up period; Device: Capsule Endoscopy; GIVEN capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first blood transfusion after randomization	Time-to-event analysis. Patients will be provided an index card on which they will record the date of their first blood transfusion after randomization	12 month follow up period

Secondary Outcome Measures

Outcome Measure	Time Frame
Total number of blood transfusions	3, 6, 9, and 12 months
Total number of hospitalizations	3, 6, 9, and 12 months
Persistent Iron Deficiency Anemia as measured by ferritin and hemoglobin	1, 3, 6, and 12 months
Total number of bleeding-related procedures performed after randomization	3, 6, 9, and 12 months
Mortality	3, 6, 9, and 12 months

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Andrew Brock, MD, Medical University of South Carolina

Publications and helpful links

General Publications

• Goddard AF, James MW, McIntyre AS, Scott BB; British Society of Gastroenterology. Guidelines for the management of iron deficiency anaemia. Gut. 2011 Oct;60(10):1309-16. doi: 10.1136/gut.2010.228874. Epub 2011 May 11.
• Gordon S, Bensen S, Smith R. Long-term follow-up of older patients with iron deficiency anemia after a negative GI evaluation. Am J Gastroenterol. 1996 May;91(5):885-9.
• McLoughlin MT, Tham TC. Long-term follow-up of patients with iron deficiency anaemia after a negative gastrointestinal evaluation. Eur J Gastroenterol Hepatol. 2009 Aug;21(8):872-6. doi: 10.1097/MEG.0b013e328321836c.
• Laine L, Sahota A, Shah A. Does capsule endoscopy improve outcomes in obscure gastrointestinal bleeding? Randomized trial versus dedicated small bowel radiography. Gastroenterology. 2010 May;138(5):1673-1680.e1; quiz e11-2. doi: 10.1053/j.gastro.2010.01.047. Epub 2010 Feb 2.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2013
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 4, 2013
• First Submitted That Met QC Criteria: April 17, 2013
• First Posted (Estimate): April 22, 2013

Study Record Updates

• Last Update Posted (Actual): June 14, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Hemorrhage; Gastrointestinal Hemorrhage
• Other Study ID Numbers: Pro00023612

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes