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Rifaximin and Misoprostol Combination Therapy for Healing of Small Bowel Ulcers in Aspirin Users

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ClinicalTrials.gov Identifier: NCT03962283
Recruitment Status : Not yet recruiting
First Posted : May 24, 2019
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
Francis KL Chan, Chinese University of Hong Kong

Brief Summary:

Background: Investigators have previously shown that misoprostol can heal small bowel ulcers in aspirin users with small bowel bleeding. However, the rate of small-bowel mucosal healing was low with use of misoprostol alone. There is evidence to suggest that bacteria contribute to the development aspirin-induced ulcers and antibiotics may be useful in its treatment. Rifaximin, a non-absorbed oral antibiotic that target the gastrointestinal tract have been shown to be safe and effective in a few other gastrointestinal conditions.

Small bowel capsule is the most sensitive and non-invasive way to investigate the small bowel. It plays an important role in obscure GIB investigations.

Aims: The aim of this randomized study is to test the hypothesis that misoprostol combined with rifaximin is superior to misoprostol alone for healing of small bowel ulcers in aspirin users complicated by small bowel bleeding.

Study design: 8-week double-blind randomized trial


Condition or disease Intervention/treatment Phase
Small Bowel Disease Rifaximin Drug: Rifaximin Drug: Placebo oral tablet Phase 2 Phase 3

Detailed Description:

Aspirin is one of the most commonly prescribed drugs worldwide It is widely used as the first line agent for prevention and treatment of heart diseases and stroke. It is well recognized that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are associated with risk of upper gastrointestinal (the stomach) bleeding. It is increasingly recognized to have adverse effects in the small bowel, including ulcers resulting in bleeding.

Bleeding from the small bowel has been very difficult to diagnose as it is beyond the reach of the conventional endoscopy. But with advances in endoscopic technique, video capsule endoscopy is now available to visualize the whole of the digestive tract. Capsule endoscopy is the size and shape of a pill which contains a tiny camera. After ingesting the capsule, pictures are taken inside of the gastrointestinal tract. Capsule endoscopy is now recommended to be a noninvasive test to identify source of small bowel bleeding.

Investigators have recently shown that misoprostol can heal small bowel ulcers in aspirin users with small bowel bleeding. However, the complete healing rate with misoprostol alone was only 40%. This suggests that we should continue to investigate for additional therapies in order to achieve higher success rate of healing of aspirin-induced small bowel ulcers.

Rifaximin is a non-absorbed oral antibiotic that targets the gastrointestinal tract. It was first described in 1982 and introduced into the Italian market 5 years later. Since then, rifaximin has had U.S. Food and Drug Administration (FDA) approval for treatment of travellers' diarrhea (year approved = 2004), hepatic encephalopathy (year approved=2010), irritable bowel syndrome (IBS) with diarrhea (year approved= 2015). Unlike the systematically available antibiotics, it allows localized enteric targeting of pathogens and is associated with minimal risk of systemic toxicity or side effects. In addition, the restricted use of non-absorbed oral antibiotics should also reduce the development of wide spread resistance.

The aim of this study is to test the hypothesis that the combination therapy of rifaximin and misoprostol is superior to misoprostol alone for healing of small bowel ulcers in aspirin users complicated by small bowel bleeding.

Participants are invited to this study because some predefined lesions are detected by the small bowel capsule endoscopy. Participants will be randomly assigned to receive either a combination therapy of misoprostol and rifaximin or misoprostol and rifaximin placebo for 8 weeks. Participants will be contacted by telephone after 1 week for any adverse events. Participants will then return at Week 8 to undergo a follow-up capsule endoscopy. Lab tests, drug compliance, and adverse events will be assessed.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Rifaximin and Misoprostol Combination Therapy for Healing of Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding: A Double Blind Randomized Trial
Estimated Study Start Date : July 1, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Rifaximin
ASA daily + misoprostol + Rifaximin (Rifaximin group)
Drug: Rifaximin
Rifaximin 200mcg four times daily

Placebo Comparator: Rifaximin Placebo
ASA daily + misoprostol + Placebo Rifaximin (Placebo group)
Drug: Placebo oral tablet
Placebo Rifaximin four times daily




Primary Outcome Measures :
  1. Healing of small bowel ulcers [ Time Frame: 8 weeks after randomization ]
    Capsule endoscopy will be performed to check if there is complete healing of small bowel ulcers, with or without red spots.


Secondary Outcome Measures :
  1. Change in numbers of ulcer/erosions [ Time Frame: 8 weeks after randomization ]
    Change in numbers of ulcer/erosions from baseline within and between groups

  2. Change in blood hemoglobin level [ Time Frame: 8 weeks after randomization ]
    Change in blood hemoglobin level from baseline within and between groups



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Suspected small bowel overt bleeding - melena or hematochezia with or without a source of bleeding from gastroscopy and colonoscopy
  • Suspected small bowel occult blood loss - defined as a significant decrease in hemoglobin (> 2g/dL), without a source of bleeding from gastroscopy and colonoscopy, confirmed iron deficiency anemia, and absence of other identifiable causes for hemoglobin decrease (e.g. fluid overload, progressive renal failure, malnutrition, or other hematological disorders such as hemolysis or malignancies)
  • Continuous use of aspirin for the duration of the trial
  • Age ≥ 18
  • Written informed consent obtained

Exclusion Criteria:

  • Increased risk of capsule retention (e.g. gastric outlet obstruction, bypass surgery, Crohn's disease or suspected small bowel stricture)
  • Abnormal findings on gastroscopy that may account for bleeding episode: clean-based ulcer >2 cm or >5 erosions, esophageal varices, grade C or D erosive esophagitis, vascular malformations
  • Unable to swallow the capsule endoscopy
  • Terminal illness
  • Concomitant use of NSAIDs, sucralfate, rebamepide, antibiotics, corticosteroids (prednisolone >7.5 mg daily or equivalent), and iron supplement
  • Pregnancy (except LMP within 7 days) or women of child-bearing age without regular use of contraception
  • Contraindications to colonoscopy or capsule endoscopy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03962283


Contacts
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Contact: Carmen Kee, MPH +852 3505 3855 carmenkee@cuhk.edu.hk
Contact: Jessica Ching, MPH +852 3505 3524 jching@cuhk.edu.hk

Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
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Principal Investigator: Francis Chan, MD Chinese University of Hong Kong

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Responsible Party: Francis KL Chan, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT03962283     History of Changes
Other Study ID Numbers: MISO RF
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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

Additional relevant MeSH terms:
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Aspirin
Misoprostol
Rifaximin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Oxytocics
Anti-Bacterial Agents
Anti-Infective Agents