Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy

• Register: ClinicalTrials.gov
• Last refreshed on: 24 April 2023
• Main ID: NCT02772965
• Date of registration: 27/04/2016
• Prospective Registration: Yes
• Primary sponsor: University of North Carolina, Chapel Hill
• Public title: Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy COMBINE
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Pragmatic Clinical Trial To Evaluate The Effectiveness Of Low Dose Oral Methotrexate In Patients With Pediatric Crohn's Disease Initiating Anti-TNF Therapy
• Date of first enrolment: October 2016
• Target sample size: 306
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02772965
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Michael D Kappelman, MD
• Affiliation: University of North Carolina, Chapel Hill

Key inclusion & exclusion criteria

Inclusion Criteria:

- Pediatric Crohn's Disease (PCD) patients, < 21 years of age, =20 kg, initiating
anti-TNF therapy with infliximab or adalimumab (including biosimilars).

- 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:

- Prior use of anti-TNF or other biological therapy for CD

- 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



Age minimum: N/A
Age maximum: 20 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pediatric Crohn's Disease

Intervention(s)

Drug: Methotrexate

Other: Sugar pill (placebo)

Primary Outcome(s)

Percent of Participants Experiencing Treatment Failure [Time Frame: From randomization until treatment failure, assessed up to 3 years.]

Secondary Outcome(s)

Mean Patient Reported Outcome Measurement and Information System (PROMIS ) Pain Interference T-score-52 Weeks [Time Frame: Weeks 52 from randomization]

Percent of Patients With Positive Anti-TNF Antibody [Time Frame: Between 6 months and 2 years from randomization]

Mean Patient Reported Outcome Measurement and Information System (PROMIS ) Pain Interference T-score-week 104 [Time Frame: 104 weeks from randomization]

Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T Score-week 104 [Time Frame: 104 weeks from randomization]

Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T Score-week 52 [Time Frame: Week 52 from randomization]

Secondary ID(s)

16-0476

1U19AR069525-01

PCD-MTX-001

PCS-1406-18643

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

The Leona M. and Harry B. Helmsley Charitable Trust

Children's Hospital Medical Center, Cincinnati

ImproveCareNow (ICN)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Grifols Diagnostics Solutions, Inc

National Institutes of Health (NIH)

Patient-Centered Outcomes Research Institute

Results

• Results available: Yes
• Date Posted: 12/04/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02772965