COMPARE - Pediatric Inflammatory Bowel Disease (PIBD)

Официальное название

Clinical Outcomes of Medications Post Anti-TNF: Researching Effectiveness in Pediatric IBD

Обзор

The purpose of the study is to compare the clinical effectiveness and safety of newer inflammatory bowel disease (IBD) medications in anti-tumor necrosis factor (TNF) refractory patients with pediatric IBD (PIBD). Refractory means that there was no clinical response to anti-tumor necrosis factor (TNF) drugs or that the if there was a response, it is no longer present. The main question this study aims to answer is: Are the newer medications used to treat IBD just as safe and effective for treating IBD in children. Participants will already be taking these newer medications as assigned by their regular health care provider.Participants' care will be managed by their regular healthcare provider as part of usual (standard) care for those with PIBD. While taking these medications, participants will be asked to answer questions about their symptoms and health periodically over the course of the study.

Подробное описание

COMPARE is a multi-center, observational cohort study that includes both prospective and retrospective components and two patient population cohorts-Crohn's disease (CD) and ulcerative colitis (UC). The study will recruit pediatric IBD patients initiating non-anti-TNF biologics and small molecules that are FDA-approved for adult populations. The primary analyses in each cohort will compare the two most frequently used classes, with all IL-23 agents analyzed as a single class. Secondary comparisons will be conducted for any classes initiated by at least 50 participants. The investigators will also perform a retrospective cohort study using EHR data extracted from participating sites.

IL-23 agents could be any of the following medications:

* Vedolizumab (trade name Entyvio™) * Ustekinumab (trade name Stelara™) * Risankizumab (trade name Skyrizi™) * Guselkumab (trade name Tremfya™) * Mirikizumab (trade name Omvoh™) * Tofacitinib (trade name Xeljanz™) * Upadacitinib (trade name Rinvoq™)

While taking these medications, participants (or parent/caregiver proxies) will complete patient-reported outcome surveys (PROS) at baseline, every 2 months for the first 12 months, and every 6 months during the 2nd and 3rd years of follow-up. The surveys will collect information about the participants' general health and well-being while taking these medications.

Clinical follow-up will occur in the context of routine care (e.g., clinic visits, telehealth encounters) for a minimum of 1-year and up to 3 years after the index date, regardless of whether the participant remains on the index treatment. The study anticipates relatively standard follow-up for each participant, based on best clinical practice, while allowing for natural variation.

The study will collect data abstracted from the medical charts of enrolled participants. Baseline data, including potential confounders described in the statistical analysis plan, will be collected by sites upon participant enrollment or shortly thereafter. Follow-up data will be collected with each outpatient gastrointestinal (GI) visit, hospitalization, surgery, colonoscopy, imaging test (MRI, CT, intestinal ultrasound), laboratory test (unless electronically captured), IBD medication change, and adverse events.

In addition, structured electronic health record (EHR) data on enrolled participants will be extracted using automated queries utilizing the PCORnet® PCORnet Common Data Model (CDM) to supplement case report forms. EHR data extraction will include laboratory values, anthropometrics, emergency department (ED) visits (and diagnosis codes), hospitalizations (and diagnosis codes), antibiotic/antiviral prescriptions, encounter dates, and diagnosis codes for events of special interest (e.g., infections, malignancy, blood clots).

The study will collect and record adverse events from participants and their caregivers, as well as via regular EHR queries using the PCORnet® CDM.

Prospective enrollment is expected to take approximately 36 months with a minimum follow-up of 12 months for each participant (maximum of 36 months).

Первичные конечные точки

• Measure of Crohn's disease (CD) impact on patients' daily lives (TUMMY CD) [Срок оценки: Baseline, months 2, 4, 6, 8, 10, 12, 18, 24, 30, 36]
• Measures of ulcerative colitis (UC) impact on patients' daily lives (TUMMY UC) [Срок оценки: Baseline, months 2, 4, 6, 8, 10, 12, 18, 24, 30, 36]
• PROMIS Symptom Measure of Irritable Bowel Disease (IBD) [Срок оценки: Baseline, months 2, 4, 6, 8, 10, 12, 18, 24, 30, 36]
• Change in Pediatric PROMIS® Patient-Reported Outcome (PRO) Pain Interference Score for Crohn's Disease and Ulcerative Colitis (CD and UC) [Срок оценки: Baseline, months 6, 12, 18, 24, 30, 36]
• Change in Pediatric PROMIS® Fatigue Score for Crohn's Disease and Ulcerative Colitis (CD and UC) [Срок оценки: Baseline, months 6, 12, 18, 24, 30, 36]
• Change in Pediatric PROMIS® Anxiety Score for Crohn's Disease and Ulcerative Colitis (CD and UC) [Срок оценки: Baseline, months 6, 12, 18, 24, 30, 36]
• Change in Pediatric PROMIS® Depression Score for Crohn's Disease and Ulcerative Colitis (CD and UC) [Срок оценки: Baseline, months 6, 12, 18, 24, 30, 36]
• Change in sPCDAI Score for Crohn's Disease [Срок оценки: Each clinic visit (baseline through follow-up, up to 3 years)]
• Change in Pediatric Ulcerative Colitis Activity Index (PUCAI) Score [Срок оценки: Each clinic visit (baseline through follow-up, up to 3 years)]

Вторичные конечные точки (4)

• Change in Fecal Calprotectin Concentration (CD and UC) [Срок оценки: 12 months after after taking prescribed medication for CD or UC]
• Number of Participants Experiencing Adverse Events (CD and UC) [Срок оценки: After medication administration and every 3 months, up to 3 years]
• Proportion of Participants Experiencing Adverse Events (CD and UC) [Срок оценки: After medication administration and every 3 months, up to 3 years]
• Exploration of Heterogeneity of Treatment Effects (HTE) Across Clinical Subgroups (CD and UC) [Срок оценки: Baseline through follow -up for up to 3 years]

Критерии участия

Критерии включения

• Age < 18 years at study enrollment
• Diagnosis of CD, UC, or IBD-U by standard diagnostic criteria
• Prior non-response or loss of response to one or more anti-TNF agents
• Planning to initiate treatment with any of the following comparator agents: vedolizumab (α4β7 integrin antibody), ustekinumab (anti-IL-12/23 antibody), risankizumab, guselkumab, or mirikizumab, (IL-23 inhibitors), tofacitinib (JAK inhibitor), and upadacitinib (JAK inhibitor). Biosimilars or generic medications for any of the above will also be allowed and handled/analyzed in an identical manner to originators.
• Ability to provide child assent, if required per regulatory or local institutional guidelines, and parental informed consent in English or Spanish

Критерии исключения

• Plans to change care to a different center within 1 year
• Prior use of a comparator agent (i.e., only patients starting their first comparator medication as monotherapy following anti-TNF will be eligible)
• Contraindication to any of the treatments under investigation
• Patients with UC or IBD-U who have undergone colectomy
• Patients with current ostomy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 4 центра

• University of North Carolina at Chapel Hill — Chapel Hill
• Atrium Health — Charlotte
• Duke Health System — Durham
• University of Pittsburgh Medical Center, Children's Hospital — Pittsburgh

Идентификаторы

NCT: NCT07198113 · 25-2019 · Pro00118431

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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