The purpose of this study is to compare the effectiveness and safety of a strategy of switching to an alternative targeted immunomodulator (TIM) therapy to treat to a target of endoscopic remission, versus continuing index TIM in patients with inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis \[UC\]) in symptomatic remission with moderate to severe endoscopic inflammation despite optimization of index TIM in a real-world setting.
This is a pragmatic, open-label, multicenter randomized control trial (RCT) conducted in asymptomatic patients with IBD who have persistent moderate to severe endoscopic inflammation despite optimization of index TIM. This study plans to recruit approximately 216 participants in the United States, who will either switching to treatment with alternative TIM to treat to a target of endoscopic remission or continue index optimized TIM. After randomization, patients will be followed prospectively within routine clinical practice for up to 2 years (104 weeks); 156 patients will be followed for the full 104 weeks, whereas 60 patients will be followed for a variable time period between 52 to 104 weeks. This trial will be conducted within select active sites in the United States and Canada The primary outcome will be time from randomization to treatment failure, as a composite of: 1. Moderate severe symptomatic relapse based on PRO2 (2-item patient reported outcome), with objective confirmation of inflammation within 2 months of event (fecal calprotectin \[FC\] \>150 mcg/g, or C reactive protein \[CRP\] \>5mg/L, or endoscopy showing moderate-severe inflammation, or magnetic resonance enterography (MRE)/computed tomography enterography (CTE)/intestinal ultrasound (IUS) showing active inflammation) with need for escalation of therapy; 2. Need for rescue therapy with corticosteroids for a documented symptomatic IBD flare; 3. IBD related hospitalization; 4. IBD-related surgery; 5. IBD-related structural complications (CD: symptomatic stricture, fistula or abscess; UC: symptomatic stricture); 6. Treatment-emergent adverse event requiring drug discontinuation. Secondary outcomes will include time from randomization to each of the components in the primary outcome, quality of life (overall quality of life, fatigue, IBD-related disability), burden of treatment (financial burden, burden of monitoring, treatment side effects), treatment satisfaction, and safety. In compliance with the pragmatic methodology of this study embedded in routine clinical care, there is no study visit mandated per study protocol. Participant visit schedules will follow local SOC with any additional visits at the treating physician's discretion. Data on all effectiveness, treatment burden and safety outcomes will be captured using a REDCap (Research Electronic Data Capture) database hosted at CCF. Data for the study will be extracted from medical record information and entered into the EDC system at baseline and then approximately every 6 months (at a minimum) thereafter, up to a 2-year follow-up period. Patient-reported outcome (PRO) measures (self-assessment questionnaires) will be utilized in this study to determine primary (efficacy) and secondary (quality of life and treatment burden and satisfaction) outcomes. Participants will complete the PRO2 at baseline and approximately every 12 weeks during the up to 2-year follow-up period; additional questionnaires (IBD-Control, PROMIS-7, Short Inflammatory Bowel Disease Questionnaire \[SIBDQ\], IBD Disability Index \[IBD-DI\], Treatment Burden Questionnaire, and Treatment Satisfaction Questionnaire for Medication) will be completed at baseline (following randomization) and up to 3 more additional times during the up to 2-year follow-up period.
Patients randomized to a strategy of switching TIM will be switched to one of the preferred agents recommended by clinical guidelines and covered by the patients' insurance formulary as part of routine care, and at the discretion of the site investigator and treating provider. No study-related medications will be provided. Patients (and their providers) in either treatment arm will be allowed to stop or start new TIMs and other IBD-directed therapies in case of symptomatic relapse or intolerance to therapies, at the discretion of the treating provider-patient team.
Mayo Clinic Arizona
Scottsdale, Arizona, United States
Time to Treatment Failure
Time to treatment failure, as a composite of: (1) moderate severe symptomatic relapse based on PRO2, with objective confirmation of inflammation within 2 months of event (FC \>250 mcg/g, or CRP \>5mg/L, or endoscopy showing moderate-severe inflammation, or MRE/CTE/IUS showing active inflammation) with need for escalation of therapy; (2) need for rescue therapy with corticosteroids for a documented symptomatic IBD flare; (3) IBD related hospitalization; (4) IBD-related surgery; (5) IBD-related structural complications (CD: symptomatic stricture, fistula or abscess; UC: symptomatic stricture); (6) treatment-emergent adverse event requiring drug discontinuation
Time frame: From randomization up to 104 weeks
Treatment failure as defined in the composite primary outcome
Treatment failure as defined in the composite primary outcome
Time frame: Binary, up to 104 weeks
Time to each individual component of the composite primary outcome
Time to each individual component of the composite primary outcome
Time frame: From randomization up to 104 weeks
Overall Quality of Life
A) Scores of the SIBDQ. B) Scores of the IBD-Control. C) Scores of the PROMIS 7 scale. D) Scores of the on IBD-DI.
Time frame: Continuous, up to 104 weeks or Early Discontinuation
Treatment Burden/Satisfaction
A) Scores of Treatment Burden Questionnaire, including medication, time and administrative, lifestyle change, social life and financial burden. B) Scores of Treatment Satisfaction Questionnaire for Medication, measuring treatment satisfaction across domains of effectiveness, side effects, convenience and global satisfaction. C) Scores of the CoPaQ, including out-of-pocket costs, for management of IBD, including treatment, monitoring, outpatient visits, and any unplanned healthcare utilization.
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
216
Hoag Hospital
Irvine, California, United States
RECRUITINGUC San Diego Health
La Jolla, California, United States
RECRUITINGCedars-Sinai
Los Angeles, California, United States
RECRUITINGSutter Health
Palo Alto, California, United States
RECRUITINGUniversity of Colorado
Aurora, Colorado, United States
RECRUITINGYale University
New Haven, Connecticut, United States
RECRUITINGMedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
RECRUITINGMayo Clinic Jacksonville
Jacksonville, Florida, United States
RECRUITINGAdvent Health
Orlando, Florida, United States
RECRUITING...and 14 more locations
Time frame: Continuous, up to 104 weeks or Early Discontinuation
Overall Safety
A) Treatment-related serious adverse events (SAEs) or unexpected SAEs. B) Serious infections, defined as infections requiring hospitalization and/or intravenous antibiotics.
Time frame: Continuous, up to 104 weeks or Early Discontinuation