Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy
NCT ID: NCT02772965
Last Updated: 2023-04-12
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
306 participants
INTERVENTIONAL
2016-10-31
2022-04-07
Brief Summary
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Detailed Description
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Number of subjects: 425 Duration of treatment for each subject: up to 156 weeks (3 years)
The primary endpoint is percent of patients who experienced treatment failure over time.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Methotrexate
Methotrexate (10, 12.5, or 15 mg), once weekly. Weight-based dosing. Ondansetron (4 mg), twice weekly, 1 hour prior to methotrexate dose and the morning after methotrexate dose.
Folic Acid (1 mg) daily
Methotrexate
1. Oral methotrexate (MTX): The weekly dose will be 15 mg for children ≥ 40kg, 12.5 mg for children 30 to \<40 kg, and 10 mg for children 20 to \<30 kg.
2. A twice per week, 4mg dose of ondansetron will be provided as pre-treatment to prevent nausea (study provider may opt-out of this component based on clinical judgement).
3. A 1 mg dose of folic acid per day will be provided. This will help to reduce the risk of side effects in the MTX group.
Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.
Sugar pill (placebo)
Placebo for methotrexate, once weekly. Placebo for ondansetron, twice weekly, 1 hour prior to methotrexate placebo dose and the morning after methotrexate placebo dose.
Folic Acid (1 mg) daily
Sugar pill (placebo)
1. Placebo for methotrexate: The weekly dose will mimic that of methotrexate.
2. Placebo for ondansetron: The weekly dose will mimic that of ondansetron (study provider may opt-out of this component based on clinical judgement).
3. A 1 mg dose of folic acid per day will be provided to maintain blinding.
Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.
Interventions
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Methotrexate
1. Oral methotrexate (MTX): The weekly dose will be 15 mg for children ≥ 40kg, 12.5 mg for children 30 to \<40 kg, and 10 mg for children 20 to \<30 kg.
2. A twice per week, 4mg dose of ondansetron will be provided as pre-treatment to prevent nausea (study provider may opt-out of this component based on clinical judgement).
3. A 1 mg dose of folic acid per day will be provided. This will help to reduce the risk of side effects in the MTX group.
Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.
Sugar pill (placebo)
1. Placebo for methotrexate: The weekly dose will mimic that of methotrexate.
2. Placebo for ondansetron: The weekly dose will mimic that of ondansetron (study provider may opt-out of this component based on clinical judgement).
3. A 1 mg dose of folic acid per day will be provided to maintain blinding.
Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Diagnosis of Crohn's Disease (CD) established confirmed by the treating clinician, and established by standard clinical criteria (radiography, endoscopy, histology).
* Ability to provide parental permission and child assent (where applicable), or adult consent for patients ages 18-20.
Exclusion Criteria
* Lack of stable home address that study medications can be mailed to
* Anticipated short length of follow up at study center (plans for family to move, transition to adult GI (gastrointestinal) provider, etc.). Patients expected to leave practice \< 12 months from enrollment should not be enrolled.
* Concurrent pelvic or abdominal abscess. A recent history of abdominal or pelvic abscess, which is controlled, does not exclude the subject.
* Prior intra-abdominal surgery without a clinically significant relapse (i.e. patients starting on anti-TNF for post-op prophylaxis or for endoscopic recurrence only should not be included)
* Receipt of a live virus vaccine within the last 30 days
* Pregnancy, planning to become pregnant, or high risk of pregnancy as determined by the local investigator
* Breastfeeding
* Refusal to stay abstinent or utilize 2 forms of birth control while on study medication (for female patients)
* BMI \> 98% for gender and age
* Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years). A recent history of basal cell or squamous cell carcinoma, which is considered surgically cured, does not exclude the subject.Those with a recent history of colonic adenoma or dysplastic lesions should be excluded.
* Known high alcohol consumption (more than seven drinks per week)
* Patients with serum albumin \< 2.5 g/dl
* Patients with white blood cell count (WBC) \< 3.0 x109th/L
* Patients with platelet count \< 100 x109th/L
* Patients with initial elevation of liver enzymes (AST or ALT) \> 1.5 times above normal limit
* Patients with known active infection with Clostridium difficile (C. difficile) (untreated infection based on clinician assessment does not apply to colonization or infection controlled with current or prior treatment.)
* Patients with pre-existing hepatic disease
* Patients with pre-existing renal dysfunction (creatinine \> 0.8 for children age\<10, creatinine \> 1.2 mg/dl for children age 10-18, and creatinine \> 1.5 mg/dl for adults age 18 years and older).
* Patients with a pre-existing chronic lung disease other than well controlled asthma
* Current treatment with one of the following drugs: Probenecid (Probalan), Acitretin (Soriatane), Streptozocin (Zanosar), Azathioprine (Imuran, Azasan), 6-mercaptopurine (Purinethol, Purixan)
* Other concerns about the patient/family's ability to participate in the study
20 Years
ALL
No
Sponsors
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Patient-Centered Outcomes Research Institute
OTHER
ImproveCareNow (ICN)
OTHER
The Leona M. and Harry B. Helmsley Charitable Trust
OTHER
Children's Hospital Medical Center, Cincinnati
OTHER
Grifols Diagnostics Solutions, Inc
UNKNOWN
National Institutes of Health (NIH)
NIH
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
NIH
University of North Carolina, Chapel Hill
OTHER
Responsible Party
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Principal Investigators
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Michael D Kappelman, MD
Role: STUDY_DIRECTOR
University of North Carolina, Chapel Hill
Locations
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Children's of Alabama
Birmingham, Alabama, United States
Stanford Children's Health
Alto, California, United States
Yale-New Haven Children's Hospital
New Haven, Connecticut, United States
Nemours Children's Health System - Wilmington
Wilmington, Delaware, United States
Nemours Children's Health System - Jacksonville
Jacksonville, Florida, United States
Nicklaus Children's Hospital
Miami, Florida, United States
Nemours Children's Health System - Orlando
Orlando, Florida, United States
Children's Healthcare of Atlanta at Egleston/Emory University
Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
University of Iowa Children's Hospital
Iowa City, Iowa, United States
MassGeneral Hospital for Children
Boston, Massachusetts, United States
Boston Children's Hospital
Boston, Massachusetts, United States
University of Michigan | CS Mott Children's Hospital
Ann Arbor, Michigan, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
St. Louis Children's Hospital | Washington University
St Louis, Missouri, United States
Children's Hospital and Medical Center Omaha
Omaha, Nebraska, United States
Mount Sinai Kravis Children's Hospital
New York, New York, United States
Upstate Golisano Children's Hospital
Syracuse, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Levine Children's Hospital
Charlotte, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies & Children's Hospital
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Dayton Children's Hospital
Dayton, Ohio, United States
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, United States
The University of Vermont Children's Hospital
Burlington, Vermont, United States
Pediatric Specialists of Virginia
Fairfax, Virginia, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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References
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Kappelman MD, Wohl DA, Herfarth HH, Firestine AM, Adler J, Ammoury RF, Aronow JE, Bass DM, Bass JA, Benkov K, Tobi CB, Boccieri ME, Boyle BM, Brinkman WB, Cabera JM, Chun K, Colletti RB, Dodds CM, Dorsey JM, Ebach DR, Entrena E, Forrest CB, Galanko JA, Grunow JE, Gulati AS, Ivanova A, Jester TW, Kaplan JL, Kugathasan S, Kusek ME, Leibowitz IH, Linville TM, Lipstein EA, Margolis PA, Minar P, Molle-Rios Z, Moses J, Olano KK, Osaba L, Palomo PJ, Pappa H, Park KT, Pashankar DS, Pitch L, Robinson M, Samson CM, Sandberg KC, Schuchard JR, Seid M, Shelly KA, Steiner SJ, Strople JA, Sullivan JS, Tung J, Wali P, Zikry M, Weinberger M, Saeed SA, Bousvaros A. Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial. Gastroenterology. 2023 Jul;165(1):149-161.e7. doi: 10.1053/j.gastro.2023.03.224. Epub 2023 Mar 31.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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PCS-1406-18643
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
PCD-MTX-001
Identifier Type: OTHER
Identifier Source: secondary_id
16-0476
Identifier Type: -
Identifier Source: org_study_id
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