Capsule Endoscopy for Severe Hematochezia

• ClinicalTrials.gov Identifier: NCT03616041
• Recruitment Status: Recruiting
• First Posted: August 6, 2018
• Last Update Posted: March 10, 2021
• Sponsor: CURE Digestive Diseases Research Center
• Information provided by (Responsible Party): Dennis M Jensen, M.D., CURE Digestive Diseases Research Center

Study Description

Brief Summary:

Patients with severe hematochezia (bright red blood per rectum) may have a bleeding source proximal to the colon. Visualization of the entire gastrointestinal tract using a second-generation colon capsule endoscopy system could improve diagnostic yields and form the basis for a new approach to early diagnosis that could change guidelines and practice management in these patients. The hypothesis of this study is that urgent colon capsule endoscopy will have higher rates of lesion localization and diagnosis and reduced time to diagnosis than the standard tagged red blood cell scanning and/or angiography. In this study, the eligible patients with severe hematochezia are enrolled to undergo an evaluation with the capsule endoscopy in addition to the standard tests including a tagged RBC scan and/or an angiogram. The outcomes in terms of diagnostic yields of the capsule endoscopy will be compared to the standard tests.

Condition or disease	Intervention/treatment
Hematochezia	Device: Second-generation colon capsule endoscopy system

Detailed Description:

Background and Significance

Currently there are no consensus guidelines for the best approach to patient with severe hematochezia. One strategy is to perform an urgent colonoscopy (following a colon purge) within 12-15 hours. Although this strategy has been associated with a decreased length of hospitalization and an improved diagnostic and therapeutic yields, it has drawbacks. A major disadvantage of performing an urgent colonoscopy is that the endoscopist can evaluate only the colon and the distal ileum, while more proximal sources of bleeding are not evaluated. Another limitation is that thorough cleansing of the colon is required to facilitate complete evaluation, identification of stigmata of recent hemorrhage and lesion diagnosis. Urgent colonoscopy is labor intense and relies on a dedicated bleeding team with expertise in both diagnosis and hemostasis. Another option for patients with persistent or recurrent hematochezia is to perform either a tagged RBC scan or an angiogram to identify the bleeding location. However, these techniques also have major disadvantages, including low diagnostic yields for severe hematochezia, requiring additional tests for diagnosis, and cannot visually detect non-bleeding stigmata of hemorrhage on lesions that can be seen during colonoscopy or by capsule endoscopy.

Research Design and Methods

This is a study of patients who being admitted to the hospital for severe hematochezia or inpatients who developed hematochezia after hospitalization for an unrelated non-GI bleeding reason. Those who meet entry criteria and lack exclusions on screening before will being asked to participate in this study.

After informed consent, patients will be a colon preparation prior to ingestion of the colon capsule. The capsule recording system will be activated once patients swallow the capsule. Once the capsule has been excreted or if the capsule stops recording images (usually 10 hours after activation), the video recorder will then be taken to a workstation and the video will be downloaded for reading.

In addition to having the capsule endoscopy, all consented patients will undergo standard tests for the initial diagnosis and management of severe hematochezia: tagged RBC scan and/or computerized tomographic angiography (CTA), magnetic resonance imaging (MRI) angiogram, or conventional angiography. Because of contra indication, MRI angiography will not be performed until the capsule has been excreted, nor will CT angiography because the capsule may interfere with interpretation. All patients will also have urgent colonoscopy after clearing the colon of blood and stool with the purge. All of these diagnostic procedures will be performed within 48 hours of GI consultation, but ideally as soon as possible.

If a bleeding site is not identified by colonoscopy, further diagnostic workup are usually performed as part of the standard of care, including anoscopy, esophagogastroduodenoscopy, push enteroscopy, or deep enteroscopy. If bleeding continues or worsens, surgery may be necessary to control the bleeding.

The GI endoscopist, nuclear medicine physician, and radiologist will be blinded to the results of the capsule endoscopy until 24 hours after the other diagnostic tests (i.e. tagged RBC scan, angiography, and endoscopy/colonoscopy) have been performed. Then the results of all tests will be unblinded. This will be done for the purpose of not delaying clinical management, but also to avoid biasing the interpretations of these diagnostic studies.

Data Collection and Monitoring Demographic data and medical history including details of co-morbid illnesses, risk factors, and characteristics of the GI bleeding will be recorded. Reasons for exclusion will be documented. Baseline physical examinations, American Society of Anesthesiology (ASA) classification, laboratory results, Blatchford-Glasgow score, units of blood products transfused, and results of the real-time viewer will also be recorded. Results of RBC scanning, angiography, capsule endoscopy, endoscopy, pathology, and surgery will be recorded. The outcomes including rates of re-bleeding or persistent bleeding, treatment of bleeding at endoscopy or radiology, need for surgery, major complications, transfusions after initial resuscitation, hospital and intensive care unit days, and death will be prospectively recorded up to the time of hospital discharge and 30 days following discharge. Subgroup analysis regarding results of urgent colonoscopy/enteroscopy will be performed to assess for differences in diagnostic yield and therapeutic interventions between different endoscopists. The number of patients who experience any difficulties in capsule swallowing will be recorded, including inability to swallow the capsule, incomplete examination of small bowel or colon, and capsule retention.

Sample size calculation Based on prior retrospective data in the CURE hemostasis database, the investigators estimate that a sample of 46 patients would be required. Four additional patients will be enrolled in case of failure of the capsule to pass through the colon or other problems with the capsule recording arise. The investigators will therefore perform the study with a sample of 50 patients in two years.

Statistical analysis methods

The primary end point of the study will be the diagnostic yield (defined as the frequency of detection and percentage of positive results) for capsule endoscopy, tagged red blood cell scan/angiography, and endoscopy for the localization of the bleeding site and/or etiologic diagnosis (e.g. definitive if stigmata of recent hemorrhage are found or presumptive if a clean lesion is diagnosed and no other lesions are found by complete evaluation). The diagnostic yield of each technique will be calculated and compared by the McNemar test for paired data using exact methods. The final diagnosis by endoscopy, angiography, pathology, and surgery will be considered the gold standard. Concordance between each diagnostic strategy will be calculated and reported with the kappa index. A P-value of less than 0.05 will be considered statistically significant.

As secondary outcomes, the sensitivity, specificity, and accuracy which will be also determined for each technique for lesion localization; absence of lesions in the foregut, small bowel, or colon; and etiologic diagnosis (definitive or presumptive).

Confidentiality:

Study data will be physically and electronically secured. All personal information will be replaced with a code de-identifying subject's information. The researchers will do their best to make sure that all subject's private information is kept confidential as possible.

Data Management Records will be labelled with a code number and then only de-identified information will be entered into our encrypted Statistical Analysis System (SAS) electronic database located at the VA West Los Angeles. No identifiable information about them will be kept in the electronic research data files. All personal information will be replaced with a code. A list linking the code and their identifiable information will be kept separate from the research data files in a locked file in the research team's office located at VA West Los Angeles. (VA CURE GI Hemostasis Research Unit). This list will be protected by the Principal Investigator (Dennis Jensen, MD) and the research team. At the end of the study, the investigators will destroy this link and no one - not even the researchers - will be able to connect their identity to the research data.

Future Use of Data After the study finishes, the research team will continue to use the patient's de-identified medical data from their medical history, laboratory results, labs, radiological, surgical, and pathology results, and colonoscopy results and information on their medical progress to continue to analyze and to report new GI research results.

Data and Safety Monitoring Plan

Adverse events The following adverse event information will be prospectively collected: capsule retention rates and those requiring endoscopic removal, perforations, aspiration, myocardial infarctions, strokes, and deaths within 30 days of enrollment.

Frequency Safety data will be collected daily while hospitalized and weekly after discharge from the hospital, up to 30 days after enrollment. Data collection will start as soon as the patient enrolls in the study and swallows the capsule.

Review Cumulative safety data will be reviewed every 30 days.

All serious adverse events (SAE's) will be reported to the IRB as mandated by the VA research service.

The safety data will be overseen by the PI and the biostatistician. All results will be reported to the IRB, who will review all SAE's.

Based upon widespread utilization and safety of capsule endoscopy for small bowel bleeding since 2001 in the U.S. and many other countries worldwide, the investigators do not expect any clinical condition which would trigger an immediate suspension of this research study.

Study Design

• Study Type: Observational
• Estimated Enrollment: 50 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Video Capsule Endoscopy for Lesion Localization and Diagnosis in Patients With Severe Hematochezia
• Actual Study Start Date: February 10, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: February 28, 2024

Groups and Cohorts

Group/Cohort

Intervention/treatment

Colon capsule endoscopy; Participant who meet the eligible criteria undergo an evaluation for severe hematochezia with a second-generation colon capsule endoscopy system in addition to standard diagnostic tests including tagged RBC scan, and/or computerized tomographic angiography (CTA), and/or conventional angiography.

Device: Second-generation colon capsule endoscopy system; The PillCam (TM) Colon 2 which is a second-generation colon capsule endoscopy system, developed by Medtronic Inc. Colon capsule endoscopy, in contrast to current generation small bowel capsules, is capable of visualizing the entire lumen and mucosa from esophagus to rectum. This can be crucial for patients being screened or evaluated for colon disorders. This new generation of colon capsule endoscopy has a battery life of at least 10 hours and preserves energy using adaptive frame rate technology.

Outcome Measures

Primary Outcome Measures :

1. The diagnostic yield tests in detecting a bleeding site and comparison of rates [ Time Frame: 30 days ]
   The diagnostic yield of the bleeding site detection (defined as the rates of detection and percentage of positive results as eg. positive test or total tests) for capsule endoscopy, tagged red blood cell scan/angiography, and endoscopy will be calculated. Rates of positive detection will be compared by the McNemar test for data using exact methods.

Secondary Outcome Measures :

1. The sensitivity for lesion localization [ Time Frame: 30 days ]
   The sensitivity for lesion localization for capsule endoscopy, tagged red blood cell scan/angiography, and endoscopy will be calculated and compared.
2. The specificity for lesion localization [ Time Frame: 30 days ]
   The specificity for lesion localization for capsule endoscopy, tagged red blood cell scan/angiography, and endoscopy will be calculated and compared.
3. The accuracy for lesion localization [ Time Frame: 30 days ]
   The accuracy for lesion localization for capsule endoscopy, tagged red blood cell scan/angiography, and endoscopy will be calculated and compared.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Patients who are hospitalized with severe GI bleeding (hematochezia) thought to be from a colonic or small bowel source, who meet entry criteria and lack exclusions.

Criteria

Inclusion Criteria:

1. 18 years old or older
2. Able to provide written informed consent or have a legal surrogate who can provide written consent
3. Presenting with evidence of severe ongoing hematochezia (i.e. passage of red blood or clots per rectum witnessed by a health care provider) and have a decrease in hemoglobin from baseline of 2 or more grams and/or transfusion of 1 or more units of red blood cells for resuscitation with either outpatient or inpatient start of severe hematochezia.

Exclusion Criteria:

1. Uncooperative, unable to give written informed consent personally or through a legal surrogate, or refuse to participate

2. Contraindication to undergo capsule endoscopy due to:

   1. Documented or suspected bowel obstruction (partial or complete)
   2. Anatomical GI abnormalities such as strictures of the foregut or small bowel
   3. Inability to swallow the capsule
   4. Presence of cardiac pacemakers or other implanted electromedical devices
3. American Society of Anesthesiology (ASA) class V (very severe co-morbidities and very poor prognosis for surgery or similar procedures)
4. Very severe GI bleeding with shock not responsive to IV fluid resuscitation and/or transfusions and IV medications to raise the systolic blood pressure
5. History of recent hematemesis (within 30 days), positive nasogastric, or orogastric (OG) aspirate suggesting an upper GI bleed
6. Presenting with recurrent hematochezia that has been previously diagnosed as anorectal bleeding

Contacts and Locations

Locations

United States, California

VA Greater Los Angeles Healthcare System; Recruiting

Los Angeles, California, United States, 90073

Contact: Dennis M Jensen, MD 310-268-3569 dennis.jensen@va.gov

Contact: Kwanmanus N Suvanamas, BS 310-478-3711 ext 43324 kwanmanus.suvanamas@va.gov

Principal Investigator: Dennis M Jensen, MD

Ronald Reagan UCLA Medical Center; Not yet recruiting

Los Angeles, California, United States, 90095

Contact: Dennis M Jensen, MD 310-268-3569 djensen@mednet.ucla.edu

Sponsors and Collaborators

CURE Digestive Diseases Research Center

Investigators

• Principal Investigator: Dennis M. Jensen, MD; VA Greater Los Angeles Healthcare System

More Information

Publications:

Strate LL. Lower GI bleeding: epidemiology and diagnosis. Gastroenterol Clin North Am. 2005 Dec;34(4):643-64. Review.

Lanas A, García-Rodríguez LA, Polo-Tomás M, Ponce M, Alonso-Abreu I, Perez-Aisa MA, Perez-Gisbert J, Bujanda L, Castro M, Muñoz M, Rodrigo L, Calvet X, Del-Pino D, Garcia S. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol. 2009 Jul;104(7):1633-41. doi: 10.1038/ajg.2009.164. Epub 2009 May 5.

Camus M, Khungar V, Jensen DM, Ohning GV, Kovacs TO, Jutabha R, Ghassemi KA, Machicado GA, Dulai GS. Origin, Clinical Characteristics and 30-Day Outcomes of Severe Hematochezia in Cirrhotics and Non-cirrhotics. Dig Dis Sci. 2016 Sep;61(9):2732-40. doi: 10.1007/s10620-016-4198-y. Epub 2016 Jun 10.

Zuckerman GR, Prakash C. Acute lower intestinal bleeding. Part II: etiology, therapy, and outcomes. Gastrointest Endosc. 1999 Feb;49(2):228-38. Review.

Jensen DM, Machicado GA. Colonoscopy for diagnosis and treatment of severe lower gastrointestinal bleeding. Routine outcomes and cost analysis. Gastrointest Endosc Clin N Am. 1997 Jul;7(3):477-98. Review.

Jensen DM, Machicado GA, Jutabha R, Kovacs TO. Urgent colonoscopy for the diagnosis and treatment of severe diverticular hemorrhage. N Engl J Med. 2000 Jan 13;342(2):78-82.

Jensen DM, Ohning GV, Kovacs TO, Jutabha R, Ghassemi K, Dulai GS, Machicado GA. Natural history of definitive diverticular hemorrhage based on stigmata of recent hemorrhage and colonoscopic Doppler blood flow monitoring for risk stratification and definitive hemostasis. Gastrointest Endosc. 2016 Feb;83(2):416-23. doi: 10.1016/j.gie.2015.07.033. Epub 2015 Jul 31.

Kanwal F, Dulai G, Jensen DM, Gralnek IM, Kovacs TO, Machicado GA, Jutabha R. Major stigmata of recent hemorrhage on rectal ulcers in patients with severe hematochezia: Endoscopic diagnosis, treatment, and outcomes. Gastrointest Endosc. 2003 Apr;57(4):462-8.

Jensen DM. Management of patients with severe hematochezia--with all current evidence available. Am J Gastroenterol. 2005 Nov;100(11):2403-6.

Spada C, Hassan C, Munoz-Navas M, Neuhaus H, Deviere J, Fockens P, Coron E, Gay G, Toth E, Riccioni ME, Carretero C, Charton JP, Van Gossum A, Wientjes CA, Sacher-Huvelin S, Delvaux M, Nemeth A, Petruzziello L, de Frias CP, Mayershofer R, Amininejad L, Dekker E, Galmiche JP, Frederic M, Johansson GW, Cesaro P, Costamagna G. Second-generation colon capsule endoscopy compared with colonoscopy. Gastrointest Endosc. 2011 Sep;74(3):581-589.e1. doi: 10.1016/j.gie.2011.03.1125. Epub 2011 May 20. Erratum in: Gastrointest Endosc. 2011 Nov;74(5):1174. Aminejab, Leila [corrected to Amininejad, Leila].

Boal Carvalho P, Rosa B, Dias de Castro F, Moreira MJ, Cotter J. PillCam COLON 2 in Crohn's disease: A new concept of pan-enteric mucosal healing assessment. World J Gastroenterol. 2015 Jun 21;21(23):7233-41. doi: 10.3748/wjg.v21.i23.7233.

• Responsible Party: Dennis M Jensen, M.D., Professor of Medicine, CURE Digestive Diseases Research Center
• ClinicalTrials.gov Identifier: NCT03616041
• Other Study ID Numbers: Colon Capsule
• First Posted: August 6, 2018
• Last Update Posted: March 10, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Dennis M Jensen, M.D., CURE Digestive Diseases Research Center:

Severe hematochezia

Additional relevant MeSH terms:

Gastrointestinal Hemorrhage; Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes