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Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02438410
Recruitment Status : Recruiting
First Posted : May 8, 2015
Last Update Posted : November 12, 2018
Information provided by (Responsible Party):
Darrell S. Pardi, M.D., Mayo Clinic

Brief Summary:
To assess if infliximab drug levels in subjects with Ulcerative Colitis predict risk of colectomy rate. Additionally, the investigators will estimate an optimal day 4 infliximab level based on the study results.

Condition or disease
Colitis, Ulcerative Inflammatory Bowel Disease IBD

Detailed Description:

Infliximab is approved for induction and maintenance of clinical remission and mucosal healing in patients with moderate to severe active ulcerative colitis, in those who have an inadequate response to conventional therapy such as IV steroids. It is typically dosed at 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter. The alternative to rescue medical therapy with infliximab is proctocolectomy with ileal pouch anastomosis, which carries risks including pouchitis, fecal incontinence, pouch failure requiring further surgical procedures and female infertility, or proctocolectomy with permanent end-ileostomy, which many patients wish to avoid. The induction regimen of 3 doses of Infliximab followed by a maintenance dose every 8 weeks is used to achieve response in hopes of avoiding colectomy. Unfortunately, a large proportion of patients are unable to achieve or sustain a clinical response over time and end up getting a colectomy.

Potential implicated pathways in non-responders include fecal wasting of infliximab and factors that accelerate drug clearance such as a large TNF (tumor necrosis factor) or CRP (C reactive protein) burden, anti-infliximab antibodies (ATI), low serum albumin, male sex and larger body size. Patients with severe ulcerative colitis who fail corticosteroids and standard dosing with infliximab usually proceed to proctocolectomy. Optimizing early infliximab blood levels in patients with moderate-severe ulcerative colitis by administering the second dose of infliximab before week 2 could improve the efficacy and further reduce the need for colectomy. However, there is a paucity in the literature as this is a relatively new school of thought. Our study will address this deficit by evaluating the relationship between early drug levels of infliximab in ulcerative colitis and colectomy rates at one and three months.

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Study Type : Observational
Estimated Enrollment : 25 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis
Study Start Date : May 2015
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Infliximab

Primary Outcome Measures :
  1. colectomy free survival [ Time Frame: 3 month ]
    The primary aim of this study is to analyze the relationship between daily infliximab levels in the first week after infusion and colectomy free survival at 3 months

Secondary Outcome Measures :
  1. colectomy free survival [ Time Frame: 1 month ]
  2. Relationships between colectomy and other potential biomarkers [ Time Frame: 3 months ]

Biospecimen Retention:   Samples Without DNA
Stool and blood laboratory data such as CBC with differential, creatinine, TNF levels, albumin, fecal calprotectin, ESR, CRP, infliximab and antibodies to infliximab levels will be obtained.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients must be scheduled to receive clinically indicated infliximab at the discretion of their treating physician during an acute hospitalization with a flare of moderate to severe UC. These will be inpatients at Mayo Clinic Rochester campus or be admitted in Mayo Clinic Health Systems. Endoscopic findings will be noted and those deemed to have moderate to severe disease activity based on the Mayo Scoring System for Assessment of Ulcerative Colitis Activity will be considered.

Inclusion Criteria

  1. Adults, ages 18-65 years
  2. Hospitalized, with a moderate -severe flare. Based on the Mayo Scoring System for Assessment of Ulcerative Colitis Activity (Mayo score of equal or greater than 6)
  3. Treatment naïve to anti TNF agents
  4. Initiation of infliximab, with or without immunomodulator such as azathioprine
  5. Ongoing use of immunomodulators such as azathioprine or 6MP is acceptable. Their initiation or continuation remains at the discretion of the treating physician

Exclusion Criteria

  1. Ongoing or prior treatment with Infliximab or other anti TNF agents
  2. Ongoing or recent (with in 1 month) administration of rescue cyclosporine
  3. Fulminant colitis requiring emergent surgery or toxic megacolon
  4. Pregnancy
  5. Infectious colitis, for example Clostridium difficile or CMV (cytomegalovirus) colitis
  6. Active infection or abscess
  7. Untreated latent or active tuberculosis (TB). Those with latent TB who are currently undergoing treatment can be included. Please refer to appendix 1 for more information on specific inclusion and exclusion criteria related to TB testing. Refer to 1.4.2 of appendix 1 for TB screening questions
  8. Active malignancy
  9. Active or history of Congestive Heart failure (CHF) or those who have received treatment for CHF
  10. Active or history of Multiple Sclerosis (MS), or those who have received treatment for MS
  11. Prisoners, institutionalized individuals, and individuals who are not capable of giving informed consent
  12. Judgement of investigator

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 identifier (NCT number): NCT02438410

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Contact: Darrell S Pardi, MD 507-284-2407
Contact: Patricia Kammer, CCRP 507-538-1827

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United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Patty Kammer         
Sponsors and Collaborators
Mayo Clinic
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Principal Investigator: Darrell S Pardi, MD Mayo Clinic

Sandborn WJ. A critical review of cyclosporine therapy in inflammatory bowel disease. Inflammatory Bowel Diseases 1995;1:48-63.
Brandse J.F. MWM, de Bruyn J., Wolbink GJ., Lowenberg M., Ponsioen C., van den Brink G.R., D'Haens G.R. Fecal Loss of Infliximab As a Cause of Lack of Response in Severe Inflammatory Bowel Disease. Gastroenterology May 2013;144:S-36.

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Responsible Party: Darrell S. Pardi, M.D., PI, Mayo Clinic Identifier: NCT02438410     History of Changes
Other Study ID Numbers: 14-005723
First Posted: May 8, 2015    Key Record Dates
Last Update Posted: November 12, 2018
Last Verified: November 2018
Keywords provided by Darrell S. Pardi, M.D., Mayo Clinic:
Colitis, Ulcerative
Additional relevant MeSH terms:
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Colitis, Ulcerative
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents