Colitis, UlcerativeNCT02438410
Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis
An observational study of Colitis, Ulcerative and Inflammatory Bowel Disease, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Colitis, Ulcerative, Inflammatory Bowel Disease, IBD
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to 4 Dec 2019
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Adults, ages 18-65 years
- 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)
- Treatment naïve to anti TNF agents
- Initiation of infliximab, with or without immunomodulator such as azathioprine
- Ongoing use of immunomodulators such as azathioprine or 6MP is acceptable. Their initiation or continuation remains at the discretion of the treating physician
Who cannot join
- Ongoing or prior treatment with Infliximab or other anti TNF agents
- Ongoing or recent (with in 1 month) administration of rescue cyclosporine
- Fulminant colitis requiring emergent surgery or toxic megacolon
- Pregnancy
- Infectious colitis, for example Clostridium difficile or CMV (cytomegalovirus) colitis
- Active infection or abscess
Show all 12Show fewer
- 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
- Active malignancy
- Active or history of Congestive Heart failure (CHF) or those who have received treatment for CHF
- Active or history of Multiple Sclerosis (MS), or those who have received treatment for MS
- Prisoners, institutionalized individuals, and individuals who are not capable of giving informed consent
- Judgement of investigator
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Colitis, Ulcerative, Inflammatory Bowel Disease, IBD
- Keywords
- infliximab, remicade, IBD, Colitis, Ulcerative
- Medical subject headings
- Colitis, Ulcerative, Inflammatory Bowel Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants to be Colectomy Free at 3 Months
Total number of participants to be colectomy free at 3 months
Measured: 3 month
Number of Participants With the Need for Colectomy Assessed by Biomarker Levels
Biomarkers markers ESR, CRP, TNF levels, and hemoglobin will be collected to assess relationships between colectomy an other potential biomarkers
Measured: 3 months
Secondary outcomes (1)
Number of Participants to be Colectomy Free at 1 Month
Total number of participants to be colectomy free at 1 month
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2015 (estimated)
- Study startMay 2015
- Primary completion4 Dec 2019
- Study completion4 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Darrell S. Pardi, M.D., Mayo Clinic
- Investigators
- Darrell S Pardi, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02438410
- Sponsor's protocol ID
- 14-005723
- Status last verified
- Apr 2022
- First submitted
- 29 Apr 2015
- Last updated
- 4 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004 May;126(6):1504-17. doi: 10.1053/j.gastro.2004.01.063.
PubMed 15168363Molodecky NA, Kaplan GG. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2010 May;6(5):339-46.
PubMed 20567592Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011 Nov 3;365(18):1713-25. doi: 10.1056/NEJMra1102942. No abstract available.
PubMed 22047562Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2004 Jul;99(7):1371-85. doi: 10.1111/j.1572-0241.2004.40036.x.
PubMed 15233681Campbell S, Travis S, Jewell D. Ciclosporin use in acute ulcerative colitis: a long-term experience. Eur J Gastroenterol Hepatol. 2005 Jan;17(1):79-84. doi: 10.1097/00042737-200501000-00016.
PubMed 15647646Sandborn WJ. A critical review of cyclosporine therapy in inflammatory bowel disease. Inflammatory Bowel Diseases 1995;1:48-63.
Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, Vilien M, Strom M, Danielsson A, Verbaan H, Hellstrom PM, Magnuson A, Curman B. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005 Jun;128(7):1805-11. doi: 10.1053/j.gastro.2005.03.003.
PubMed 15940615Waljee A, Waljee J, Morris AM, Higgins PD. Threefold increased risk of infertility: a meta-analysis of infertility after ileal pouch anal anastomosis in ulcerative colitis. Gut. 2006 Nov;55(11):1575-80. doi: 10.1136/gut.2005.090316. Epub 2006 Jun 13.
PubMed 16772310Penna C, Dozois R, Tremaine W, Sandborn W, LaRusso N, Schleck C, Ilstrup D. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut. 1996 Feb;38(2):234-9. doi: 10.1136/gut.38.2.234.
PubMed 8801203Hahnloser D, Pemberton JH, Wolff BG, Larson DR, Crownhart BS, Dozois RR. The effect of ageing on function and quality of life in ileal pouch patients: a single cohort experience of 409 patients with chronic ulcerative colitis. Ann Surg. 2004 Oct;240(4):615-21; discussion 621-3. doi: 10.1097/01.sla.0000141157.32234.9d.
PubMed 15383789Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.
PubMed 16339095Peyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel JF. Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008 Jun;6(6):644-53. doi: 10.1016/j.cgh.2008.03.014.
PubMed 18550004Brandse 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.
Ordas I, Mould DR, Feagan BG, Sandborn WJ. Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther. 2012 Apr;91(4):635-46. doi: 10.1038/clpt.2011.328. Epub 2012 Feb 22.
PubMed 22357456Gibson DJ, Heetun ZS, Redmond CE, Nanda KS, Keegan D, Byrne K, Mulcahy HE, Cullen G, Doherty GA. An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis. Clin Gastroenterol Hepatol. 2015 Feb;13(2):330-335.e1. doi: 10.1016/j.cgh.2014.07.041. Epub 2014 Jul 30.
PubMed 25086187
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT02438410
- Acronym / sponsor ID
- 14-005723
- Conditions
- Colitis, Ulcerative, Inflammatory Bowel Disease, IBD
- Keywords
- infliximab, remicade, IBD, Colitis, Ulcerative
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- 4 Dec 2019 (actual)
- Study completion
- 4 Dec 2019 (actual)
- First posted
- 8 May 2015 (estimated)
- Results
- Posted 3 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- Adults, ages 18-65 years
- 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)
- Treatment naïve to anti TNF agents
- Initiation of infliximab, with or without immunomodulator such as azathioprine
- Ongoing use of immunomodulators such as azathioprine or 6MP is acceptable. Their initiation or continuation remains at the discretion of the treating physician
Key exclusion criteria (12 listed)
- Ongoing or prior treatment with Infliximab or other anti TNF agents
- Ongoing or recent (with in 1 month) administration of rescue cyclosporine
- Fulminant colitis requiring emergent surgery or toxic megacolon
- Pregnancy
- Infectious colitis, for example Clostridium difficile or CMV (cytomegalovirus) colitis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of Participants to be Colectomy Free at 3 Months
Time frame: 3 month
Total number of participants to be colectomy free at 3 months
Number of Participants With the Need for Colectomy Assessed by Biomarker Levels
Time frame: 3 months
Biomarkers markers ESR, CRP, TNF levels, and hemoglobin will be collected to assess relationships between colectomy an other potential biomarkers
1 secondary outcome
Number of Participants to be Colectomy Free at 1 Month
Time frame: 1 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15168363Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004 May;126(6):1504-17. doi: 10.1053/j.gastro.2004.01.063.
- Background: PubMed 20567592Molodecky NA, Kaplan GG. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2010 May;6(5):339-46.
- Background: PubMed 22047562Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011 Nov 3;365(18):1713-25. doi: 10.1056/NEJMra1102942. No abstract available.
- Background: PubMed 15233681Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2004 Jul;99(7):1371-85. doi: 10.1111/j.1572-0241.2004.40036.x.
- Background: PubMed 15647646Campbell S, Travis S, Jewell D. Ciclosporin use in acute ulcerative colitis: a long-term experience. Eur J Gastroenterol Hepatol. 2005 Jan;17(1):79-84. doi: 10.1097/00042737-200501000-00016.
- BackgroundSandborn WJ. A critical review of cyclosporine therapy in inflammatory bowel disease. Inflammatory Bowel Diseases 1995;1:48-63.
- Background: PubMed 15940615Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, Vilien M, Strom M, Danielsson A, Verbaan H, Hellstrom PM, Magnuson A, Curman B. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005 Jun;128(7):1805-11. doi: 10.1053/j.gastro.2005.03.003.
- Background: PubMed 16772310Waljee A, Waljee J, Morris AM, Higgins PD. Threefold increased risk of infertility: a meta-analysis of infertility after ileal pouch anal anastomosis in ulcerative colitis. Gut. 2006 Nov;55(11):1575-80. doi: 10.1136/gut.2005.090316. Epub 2006 Jun 13.
- Background: PubMed 8801203Penna C, Dozois R, Tremaine W, Sandborn W, LaRusso N, Schleck C, Ilstrup D. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut. 1996 Feb;38(2):234-9. doi: 10.1136/gut.38.2.234.
- Background: PubMed 15383789Hahnloser D, Pemberton JH, Wolff BG, Larson DR, Crownhart BS, Dozois RR. The effect of ageing on function and quality of life in ileal pouch patients: a single cohort experience of 409 patients with chronic ulcerative colitis. Ann Surg. 2004 Oct;240(4):615-21; discussion 621-3. doi: 10.1097/01.sla.0000141157.32234.9d.
- Background: PubMed 16339095Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.
- Background: PubMed 18550004Peyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel JF. Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008 Jun;6(6):644-53. doi: 10.1016/j.cgh.2008.03.014.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darrell S Pardi, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colitis, Ulcerative and Inflammatory Bowel Disease, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants to be Colectomy Free at 3 Months (time frame: 3 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02438410, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2022.