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Anti-tumor necrosis factor (TNF) monotherapy versus combination therapy with low-dose methotrexate in pediatric Crohn's disease
Investigator (PI): Kappelman, Michael
Performing Organization (PO): (Current): University of North Carolina at Chapel Hill, School of Medicine, Department of Pediatrics, Division of Pediatric Gastroenterology / (919) 966-2435
Supporting Agency (SA): Patient-Centered Outcomes Research Institute (PCORI)
Initial Year: 2015
Final Year: 2023
Record Source/Award ID: PCORI/PCS-1406-18643
Funding: Total Award Amount: $7,885,900
Award Type: Contract
Award Information: PCORI: More information and project results (when completed)
Abstract: PCORI has identified the need for large studies that look at real-life questions faced by diverse patients, caregivers, and clinicians. To address this need, PCORI launched the Pragmatic Clinical Studies initiative in 2014. Pragmatic clinical studies allow for larger-scale studies with longer timelines to compare the benefits and harms of two or more approaches known to be effective for preventing, diagnosing, treating, or managing a disease or symptom. They focus on everyday care for a wide range of patients. This research project is one of the studies PCORI awarded as part of this program. This research project is in progress. PCORI will post the research findings on the PCORI website within 90 days after the results are final. What is the research about? Crohn's disease affects about 600,000 Americans, including approximately 40,000 children. The condition causes inflammation in the digestive tract. People with Crohn's disease experience abdominal pain, cramping, and bloody diarrhea that can reduce their quality of life and may even require hospitalization or surgery. For children, Crohn's disease often gets worse over time and may affect both physical and emotional development. Most people with Crohn's disease need lifelong treatment. Doctors may prescribe antibiotics, steroids, or other types of medicines that reduce inflammation or change the way the immune system behaves. This study focuses on children and young adults with Crohn's disease who are starting treatment with medicine called anti-TNF treatment to reduce inflammation. The study looks at whether anti-TNF treatment works better alone or with a medicine called low-dose methotrexate, which reduces the body's immune response. Who can this research help? Children and young adults with Crohn's disease, their caregivers, and their doctors can use information from this study to help choose a treatment. What is the research team doing? The research team is recruiting 425 children and young adults with Crohn's disease at up to 50 medical centers across the United States. ImproveCareNow--a network of patients, families, researchers, and health care professionals who are affected by Crohn's disease or doing research on it--is helping the team to identify people under age 21 who have Crohn's disease and are starting anti-TNF treatment. All patients in the study take anti-TNF treatment. In addition, the research team is assigning patients by chance to take either a low dose of methotrexate or a sugar pill that has no medical effect. Patients do not know whether they are receiving methotrexate or the sugar pill. The team is following patients for two years to track whether symptoms get better and whether the improvement lasts. They are also looking at whether any symptoms that reappear need to be treated with steroids, hospitalization, or surgery, and whether patients develop side effects. The research team is also tracking other symptoms that are important to patients, such as pain and tiredness. The research team is involving health care professionals in planning the study. The team is also working with an advisory group that includes patients, parents, hospitals, health care professionals, a Crohn's disease organization, pharmaceutical companies, and organizations that pay for health care. Research methods. Design: The study design is a randomized controlled trial. Population: The study population is people under 21 years with Crohn's disease who are starting anti-TNF treatment. Interventions/comparators are low-dose oral methotrexate and sugar pill. Outcomes: Outcomes are (1) primary: remission of symptoms without steroids, hospitalization, or surgery; and (2) secondary: patient-reported pain and fatigue, and occurrence of moderate or serious side effects related to treatment. The timeframe is 2-year follow-up for primary outcome.
Abstract Archived: Crohn's disease (CD), which affects about 600,000 Americans, causes abdominal pain and bloody diarrhea, leading to frequent hospitalizations, surgery, and decreased quality of life. Pediatric CD (PCD) affects about 38,000 children, is often progressive, and can impair both physical and emotional development. PCD treatment usually includes corticosteroids, anti-inflammatory aminosalicylates, immunosuppressives, or drugs that target tumor necrosis factor (TNF). We will conduct a large, pragmatic clinical trial to determine whether an intervention using an anti-TNF drug plus low-dose oral methotrexate is more effective than anti-TNF therapy alone among children with moderate-to-severe PCD who have not previously had anti-TNF therapy. Our specific aims are to (1) determine whether methotrexate, in combination with anti-TNF therapy, is more effective than anti-TNF therapy alone in the induction and subsequent maintenance of remission for 2 years; (2) compare patient-reported outcomes; (3) describe investigator-reported adverse events; and (4) collect blood serum from trial participants to facilitate future studies evaluating anti-TNF concentrations and antibody formation. Participants, recruited through the Improve Care Now (ICN) Learning Health System, will be less than 18 years old, have moderate-to-severe PCD, and be just beginning anti-TNF therapy. Participants will be randomly assigned to receive either anti-TNF therapy and oral methotrexate (combination therapy) or anti-TNF monotherapy alone; they will be followed for two years. The primary measure of effectiveness will be achieving and maintaining a symptom-free remission, without the need for steroids, hospitalization, or surgery. In addition, we will identify and prioritize a set of patient-reported outcomes that will be used as another measure of effectiveness. Finally, we will compare the occurrence of moderate or severe treatment-related side effects. We engaged clinicians in the planning of this trial and have partnered with the Crohn's and Colitis Foundation of America (CCFA), the nation's leading inflammatory bowel disease advocacy organization, as well as children's hospitals, payers, and pharmaceutical companies. An advisory board of patients, parents, the CCFA, industry, payers, and health system leaders will meet with the investigators twice yearly to review study progress, troubleshoot as needed, and help plan dissemination strategies. This study will have substantial impact on patient decision making, care, and outcomes. Conducting this trial within ICN will allow the same network that generates the research to implement evidence into practice.

MeSH Terms:
  • Administration, Oral
  • Child
  • Crohn Disease /*drug therapy
  • Humans
  • Methotrexate /*administration & dosage
  • Outcome Assessment, Health Care
  • Program Evaluation
  • Quality of Life
  • Remission Induction
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha /*antagonists & inhibitors
  • /blood
  • United States
Country: United States
State: North Carolina
Zip Code: 27599
UI: 20153605
CTgovId: NCT02772965
Project Status: Ongoing
Record History: ("2020: Project extended to 2023. Archived abstract to Abstract Archived 1 field and added new abstract. Alternate Title: Comparing treatments for children with Crohn's disease.\n2017: Project extended to 2021.",)