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Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT02438410
Recruitment Status : Recruiting
First Posted : May 8, 2015
Last Update Posted : November 12, 2018
Sponsor:
Information provided by (Responsible Party):
Darrell S. Pardi, M.D., Mayo Clinic

Tracking Information
First Submitted Date April 29, 2015
First Posted Date May 8, 2015
Last Update Posted Date November 12, 2018
Study Start Date May 2015
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 5, 2015)
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
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02438410 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: May 5, 2015)
  • colectomy free survival [ Time Frame: 1 month ]
  • Relationships between colectomy and other potential biomarkers [ Time Frame: 3 months ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis
Official Title Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis
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.
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
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.
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.
Condition
  • Colitis, Ulcerative
  • Inflammatory Bowel Disease
  • IBD
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 5, 2015)
25
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Darrell S Pardi, MD 507-284-2407 pardi.darrell@mayo.edu
Contact: Patricia Kammer, CCRP 507-538-1827 Kammer.Patricia@mayo.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02438410
Other Study ID Numbers 14-005723
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Darrell S. Pardi, M.D., Mayo Clinic
Study Sponsor Mayo Clinic
Collaborators Not Provided
Investigators
Principal Investigator: Darrell S Pardi, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date November 2018