Colitis, UlcerativeARCHNCT02799615
Anti-TNF Therapy for Refractory Colitis in Hospitalized Children
An observational study of Colitis, Ulcerative and Bowel Diseases, Inflammatory, run by Children's Hospital Medical Center, Cincinnati at 7 sites in 2 countries.
Trial summary
This multicenter study is being conducted to determine whether infliximab exposure after an initial infusion is predictive of early clinical response in hospitalized pediatric patients with severe steroid-refractory UC or IBD-U. Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Colitis, Ulcerative, Bowel Diseases, Inflammatory
- What is being tested?
- Infliximab
- How many people
- 38 participants
- Where
- 7 sitesin 2 countries
- Study dates
- May 2016to Nov 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: Research participants age 4 to 17 will be eligible for this study. Our target is a minimum of 36 evaluable research participants (to a maximum of 40) across up to 6 participating centers.
Who may be able to join
- Age criteria: ≥ 4 or < 18 years of age
- Diagnosis of UC or IBD-U by established criteria
- Admitted to the hospital
- Colitis extending beyond the rectosigmoid colon
- PUCAI ≥ 65 at admission and ≥ 45 at first dose of infliximab
- Treatment with infliximab considered by the treating physician
- Anticipated follow-up ≥ 6 months from infliximab initiation
- Permission/assent of parent/guardian and research participant.
Who cannot join
- Diagnosis of Crohn's disease
- Enteric infection with a bacterial pathogen (including clostridium difficile), per review of medical records
- Colon tissue positive for CMV by PCR, immunohistochemistry, or in situ hybridization, per review of the medical records
- Colitis currently extending only to the rectosigmoid colon (proctosigmoiditis)
- Prior treatment with infliximab or other anti-TNF agent
- Prior treatment with cyclosporine or tacrolimus
Show all 11Show fewer
- PUCAI < 45 the day of first infliximab infusion
- Pregnancy, per review of medical records and verbal report
- Other poorly controlled medical condition
- Hepatic disease (AST or Alk Phos > 3 times the upper limit of normal) in the absence of IBD associated liver disease
- Renal disease (BUN and creatinine >1.5 times the upper limit of normal)
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
Connecticut Children's Hospital Medical Center
Hartford, Connecticut, 06016
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Rhode Island Hospital
Providence, Rhode Island, 02903
About this study
Official title: Multicenter Non-Therapeutic Study of Infliximab for Severe Refractory Colitis in Hospitalized Children
This multicenter study is being conducted to determine whether infliximab exposure after an initial infusion is predictive of early clinical response in hospitalized pediatric patients with severe steroid-refractory UC or IBD-U. This pilot and feasibility study will establish the infrastructure, demonstrate feasibility, and collect preliminary data to support the full study.
Read the detailed description
This is a multicenter prospective non-interventional cohort study to identify clinical and biological markers that predict non-response in hospitalized pediatric patients with severe corticosteroid-refractory UC or inflammatory bowel disease unspecified (IBD-U) being initiated on infliximab.
Patients hospitalized with severe UC or IBD-U (PUCAI ≥ 65 on admission) and failing intravenous corticosteroids will be eligible. Blood, stool, and rectal biopsies (if sigmoidoscopy performed for clinical indications) will be collected for translational studies (Aim 3). Patients will receive infliximab per the dose and regimen determined by clinical physician. No standard dosing regimen will be used and the dose of IFX will be determined by the treating physician. Serial PUCAI scores and infliximab levels will be obtained.
Those who are eligible to participate will have serial blood samples taken in association with drug infusions to perform pharmacokinetic/pharmacodynamic modeling of infliximab exposure. Clinical response will be determined using the Pediatric UC Activity Index (PUCAI) questionnaire.
Initially, 6 centers will participate with a minimum target enrollment goal of 36 evaluable pediatric research participants (to a maximum of 40) age > 4 years or < 18 years old with UC or IBD-U (average 6/center).
The primary endpoint will be the relationship between IFX exposure (area under the curve of the PK model) and Day 7 clinical response defined as Pediatric Ulcerative Colitis Activity Index (PUCAI) ≤ 35. Secondary endpoints will be Week 8 clinical remission, and Week 26 steroid-free, colectomy-free remission. We will initially enlist 6 centers, and enroll 36-40 evaluable patients in 2 years.
This study described by this protocol is designed as pilot and feasibility study, which we anticipate will ultimately be expanded to larger study. Therefore, to demonstrate feasibility and begin the development of a biorepository on this patient population, certain biospecimens will be collected for this study and anticipated future translational studies as follows:
- Blood will be used for IFX pharmacokinetic assays (e.g. levels, antibodies) and future biomarker discovery.
- Blood DNA we anticipate will be used for genotype/phenotype correlations and genetic predictors of rapid infliximab clearance and non-response.
- Colon tissue RNA will be used for determining how local gene expression patterns predict or explain infliximab clearance or non-response.
- Colon tissue DNA we anticipate will be used for studies of how the microbiome or epigenetic changes relate to severe UC or response to infliximab.
- Colon tissue will be used for determining the relationship between tissue TNF levels (or other proteins) and infliximab clearance or non-response.
- Stool will be collected for serial measurement of fecal calprotectin and future microbiome studies
- Conditions
- Colitis, Ulcerative, Bowel Diseases, Inflammatory
- Being tested
- Infliximab
- Medical subject headings
- Colitis, Ulcerative, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called Remicade
No standard dosing regimen will be used and the dose of infliximab will be determined by the treating physician
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be the relationship between IFX exposure (area under the curve of the PK model) and Day 7 clinical response defined as Pediatric Ulcerative Colitis Activity Index (PUCAI) <35.
IFX exposure and Day 7 PUCAI
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2016 (estimated)
- Study startMay 2016
- Primary completion11 Feb 2019
- Study completionNov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 Children's Hospital Medical Center, CincinnatiThe 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
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Crohn's and Colitis Foundation
- Responsible party
- Sponsor
- Investigators
- Michael J Rosen, MD, MSCI, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02799615
- Sponsor's protocol ID
- 2014-0063; 2015-8753
- Acronym
- ARCH
- Status last verified
- Jul 2019
- First submitted
- 9 Jun 2016
- Last updated
- 10 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Whaley KG, Xiong Y, Karns R, Hyams JS, Kugathasan S, Boyle BM, Walters TD, Kelsen J, LeLeiko N, Shapiro J, Waddell A, Fox S, Bezold R, Bruns S, Widing R, Haberman Y, Collins MH, Mizuno T, Minar P, D'Haens GR, Denson LA, Vinks AA, Rosen MJ. Multicenter Cohort Study of Infliximab Pharmacokinetics and Therapy Response in Pediatric Acute Severe Ulcerative Colitis. Clin Gastroenterol Hepatol. 2023 May;21(5):1338-1347. doi: 10.1016/j.cgh.2022.08.016. Epub 2022 Aug 27.
PubMed 36031093
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Non-Therapeutic Study of Infliximab for Severe Refractory Colitis in Hospitalized Children
- ClinicalTrials.gov ID
- NCT02799615
- Acronym / sponsor ID
- ARCH / 2014-0063; 2015-8753
- Conditions
- Colitis, Ulcerative, Bowel Diseases, Inflammatory
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Crohn's and Colitis Foundation
- Study start
- May 2016
- Primary completion
- 11 Feb 2019 (actual)
- Study completion
- Nov 2019 (actual)
- First posted
- 15 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multicenter study is being conducted to determine whether infliximab exposure after an initial infusion is predictive of early clinical response in hospitalized pediatric patients with severe steroid-refractory UC or IBD-U. This pilot and feasibility study will establish the infrastructure, demonstrate feasibility, and collect preliminary data to support the full study.
Detailed description
This is a multicenter prospective non-interventional cohort study to identify clinical and biological markers that predict non-response in hospitalized pediatric patients with severe corticosteroid-refractory UC or inflammatory bowel disease unspecified (IBD-U) being initiated on infliximab.
Patients hospitalized with severe UC or IBD-U (PUCAI ≥ 65 on admission) and failing intravenous corticosteroids will be eligible. Blood, stool, and rectal biopsies (if sigmoidoscopy performed for clinical indications) will be collected for translational studies (Aim 3). Patients will receive infliximab per the dose and regimen determined by clinical physician. No standard dosing regimen will be used and the dose of IFX will be determined by the treating physician. Serial PUCAI scores and infliximab levels will be obtained.
Those who are eligible to participate will have serial blood samples taken in association with drug infusions to perform pharmacokinetic/pharmacodynamic modeling of infliximab exposure. Clinical response will be determined using the Pediatric UC Activity Index (PUCAI) questionnaire.
Initially, 6 centers will participate with a minimum target enrollment goal of 36 evaluable pediatric research participants (to a maximum of 40) age > 4 years or < 18 years old with UC or IBD-U (average 6/center).
The primary endpoint will be the relationship between IFX exposure (area under the curve of the PK model) and Day 7 clinical response defined as Pediatric Ulcerative Colitis Activity Index (PUCAI) ≤ 35. Secondary endpoints will be Week 8 clinical remission, and Week 26 steroid-free, colectomy-free remission. We will initially enlist 6 centers, and enroll 36-40 evaluable patients in 2 years.
This study described by this protocol is designed as pilot and feasibility study, which we anticipate will ultimately be expanded to larger study. Therefore, to demonstrate feasibility and begin the development of a biorepository on this patient population, certain biospecimens will be collected for this study and anticipated future translational studies as follows:
- Blood will be used for IFX pharmacokinetic assays (e.g. levels, antibodies) and future biomarker discovery.
- Blood DNA we anticipate will be used for genotype/phenotype correlations and genetic predictors of rapid infliximab clearance and non-response.
- Colon tissue RNA will be used for determining how local gene expression patterns predict or explain infliximab clearance or non-response.
- Colon tissue DNA we anticipate will be used for studies of how the microbiome or epigenetic changes relate to severe UC or response to infliximab.
- Colon tissue will be used for determining the relationship between tissue TNF levels (or other proteins) and infliximab clearance or non-response.
- Stool will be collected for serial measurement of fecal calprotectin and future microbiome studies
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Research participants age 4 to 17 will be eligible for this study. Our target is a minimum of 36 evaluable research participants (to a maximum of 40) across up to 6 participating centers.
Key inclusion criteria (8 listed)
- Age criteria: ≥ 4 or < 18 years of age
- Diagnosis of UC or IBD-U by established criteria
- Admitted to the hospital
- Colitis extending beyond the rectosigmoid colon
- PUCAI ≥ 65 at admission and ≥ 45 at first dose of infliximab
Key exclusion criteria (11 listed)
- Diagnosis of Crohn's disease
- Enteric infection with a bacterial pathogen (including clostridium difficile), per review of medical records
- Colon tissue positive for CMV by PCR, immunohistochemistry, or in situ hybridization, per review of the medical records
- Colitis currently extending only to the rectosigmoid colon (proctosigmoiditis)
- Prior treatment with infliximab or other anti-TNF agent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabAlso: RemicadeNo standard dosing regimen will be used and the dose of infliximab will be determined by the treating physician | Drug | – |
Primary outcome
The primary endpoint will be the relationship between IFX exposure (area under the curve of the PK model) and Day 7 clinical response defined as Pediatric Ulcerative Colitis Activity Index (PUCAI) <35.
Time frame: 7 days
IFX exposure and Day 7 PUCAI
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2020.
- Derived from this study: PubMed 36031093Whaley KG, Xiong Y, Karns R, Hyams JS, Kugathasan S, Boyle BM, Walters TD, Kelsen J, LeLeiko N, Shapiro J, Waddell A, Fox S, Bezold R, Bruns S, Widing R, Haberman Y, Collins MH, Mizuno T, Minar P, D'Haens GR, Denson LA, Vinks AA, Rosen MJ. Multicenter Cohort Study of Infliximab Pharmacokinetics and Therapy Response in Pediatric Acute Severe Ulcerative Colitis. Clin Gastroenterol Hepatol. 2023 May;21(5):1338-1347. doi: 10.1016/j.cgh.2022.08.016. Epub 2022 Aug 27.
- Individual participant dataSharing planned: No
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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.
Michael J Rosen, MD, MSCI principal investigator
Children's Hospital Medical Center, Cincinnati
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colitis, Ulcerative and Bowel Diseases, Inflammatory, run by Children's Hospital Medical Center, Cincinnati at 7 sites in 2 countries.
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 8 inclusion and 11 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 10 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary endpoint will be the relationship between IFX exposure (area under the curve of the PK model) and Day 7 clinical response defined as Pediatric Ulcerative Colitis Activity Index (PUCAI) <35. (time frame: 7 days). 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 NCT02799615, which also lists 1 linked publication.
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 10 Apr 2020.