Treat-to-Target of Endoscopic Remission in Patients With IBD in Symptomatic Remission

NCT ID: NCT05230173

Last Updated: 2024-04-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-05

Study Completion Date

2028-06-01

Brief Summary

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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.

Detailed Description

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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 250 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 over 2 years (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 a 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 a 2-year follow-up period.

Conditions

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Ulcerative Colitis Crohn Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Switching Targeted Immunomodulators Treatment

Participants randomized to a strategy of switching TIM will be switched to one of the preferred agents recommended by clinical guidelines and covered by the participants' 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.

For participants randomized to switch to an alternative TIM, selection of alternative agent will be determined at the discretion of the local site physician in accordance with clinical guidelines on the management of moderate to severe ulcerative colitis, and management of moderate to severe CD from the AGA and ACG.9, 34, 35 These guidelines include recommendations on positioning of TIMs for first line use (TIM-naïve patients) and second-line use (in patients with prior exposure to TIMs).

Group Type OTHER

Pragmatic

Intervention Type OTHER

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.

Continuing Index Targeted Immunomodulators Treatment

Participants randomized to a strategy of continuing TIM will continue on their concomitant therapy.

Group Type OTHER

Pragmatic

Intervention Type OTHER

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.

Interventions

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Pragmatic

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Male or nonpregnant, nonlactating females, ≥ 18 years of age.
2. An established diagnosis of CD or UC for at least 6 months based on standard clinical criteria, confirmed by the treating provider.
3. Current treatment with an approved TIM for treatment of IBD, including biologic agents (e.g., TNFα antagonists, ustekinumab, vedolizumab) and small molecule inhibitors (e.g., Janus kinase inhibitors, ozanimod), including future TIMs that become commercially available during the conduct of the trial.
4. Dose of TIM should be stable for 3 or more months prior to qualifying endoscopy/radiology. No treatment escalation of TIM or addition of IMM, corticosteroid, or mesalamines after the qualifying endoscopy/radiology procedure up to randomization is permitted. Dose de-escalation after qualifying procedure is permissible at the discretion of the treating provider.
5. In corticosteroid-free symptomatic remission based on validated PROs (PRO2 score) and deemed to be experiencing no other IBD-related symptoms in the opinion of the treating provider. Includes patients who may be in medically induced remission (on index TIM); or surgically induced remission with post-op initiation of index TIM for prophylaxis and colonoscopy/imaging performed at least 3 months after initiation/optimization of TIM showing moderate-severe bowel inflammation. Validated PROs are defined as:

1. CD: PRO2 (2-item patient reported outcome) mean daily score of abdominal pain score ≤1 and stool frequency score ≤ 3; or
2. UC: PRO2, with absence of rectal bleeding (rectal bleeding score = 0) and with stool frequency score ≤1.
6. Evidence of moderate to severe bowel inflammation on local reading of colonoscopy, flexible sigmoidoscopy, balloon-assisted enteroscopy, capsule endoscopy or MR, CT enterography, or intestinal ultrasound, performed within 6 months prior to screening, defined at the investigator's discretion or as follows:

1. CD: Colonoscopy showing moderately to severely active inflammation based on 1 of the following variables/scores:

* Simple Endoscopic Score for Crohn's Disease (SES-CD) score ≥7 or score ≥4 for those with isolated ileal disease, or
* Presence of mucosal ulcers \>5 mm in size if SES-CD has not been recorded, or
* Simplified Endoscopic Mucosal Assessment for Crohn's Disease (SEMA-CD) score ≥2, or
* Rutgeerts score i2b or higher for patients in surgically induced remission with post-operative endoscopic recurrence \[Note, either SES-CD or Rutgeerts score can be used for participants with post-operative recurrence\]; or
2. CD: MRE or CTE showing moderately to severely active inflammation based on 1 of the following variables:

* Increased bowel wall thickness, or
* Mural hyperenhancement, or
* Peri-enteric fat stranding, or
* Radiographic features of ulceration, or
* Intramural T2 signal on fat suppressed images; or
3. CD: Capsule endoscopy showing moderately to severely active small bowel disease based on Lewis score \>790 (in case the disease is not accessible via endoscopy), or per local endoscopist if Lewis score is not reported; or
4. CD: Gastrointestinal ultrasound showing at least 1 of the following variables:

* Increased bowel wall thickness \>5 mm, or
* Color doppler score \>5/cm2, or
* Bowel stenosis, or
* Bowel stratification, or
* Fatty wrapping; or
5. UC: modified MES score of 2 to 3, or documentation of any endoscopic feature that would define an MES of 2 to 3 (e.g., friability, ulceration, spontaneous bleeding, complete loss of vascular pattern), if an MES has not been recorded.
7. Eligible to receive at least 1 alternative TIM (excluding their index TIM) for the treatment of their disease per approved drug label, based on clinical and reimbursement guidelines.
8. Able to participate fully in all aspects of this clinical trial.
9. Informed consent must be obtained and documented.

Exclusion Criteria

1. Presence of ostomy or ileoanal pouches.
2. Serious underlying disease other than UC or CD that in the opinion of the investigator may interfere with the participant's ability to participate fully in the study.
3. History of alcohol or drug abuse or any other medical or health condition that in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures.
4. Prior enrolment in the current study.
5. Mild endoscopic disease activity, where treating providers would not consider switching TIM.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Baylor College of Medicine

OTHER

Sponsor Role collaborator

Crohn's and Colitis Foundation

OTHER

Sponsor Role collaborator

Western University

OTHER

Sponsor Role collaborator

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role lead

Responsible Party

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Siddharth Singh

Associate Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Siddharth Singh, MD

Role: PRINCIPAL_INVESTIGATOR

UC San Diego Health

Locations

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Hoag Hospital

Irvine, California, United States

Site Status RECRUITING

UC San Diego Health

La Jolla, California, United States

Site Status RECRUITING

Cedars-Sinai

Los Angeles, California, United States

Site Status RECRUITING

Sutter Health

Palo Alto, California, United States

Site Status RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

University of Chicago Medicine

Chicago, Illinois, United States

Site Status RECRUITING

Dartmouth Hitchcock

Lebanon, New Hampshire, United States

Site Status RECRUITING

Saratoga Schenectady Gastroenterology Associates

Burnt Hills, New York, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Cornell University

New York, New York, United States

Site Status RECRUITING

University of Rochester

Rochester, New York, United States

Site Status RECRUITING

Hightower Clinical

Oklahoma City, Oklahoma, United States

Site Status NOT_YET_RECRUITING

Oregon Clinic

Portland, Oregon, United States

Site Status WITHDRAWN

Gastroenterology Associates

Providence, Rhode Island, United States

Site Status RECRUITING

GastroOne

Germantown, Tennessee, United States

Site Status WITHDRAWN

University of Texas Southwestern

Dallas, Texas, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

University of Utah Health

Salt Lake City, Utah, United States

Site Status RECRUITING

University of Virginia

Charlottesville, Virginia, United States

Site Status WITHDRAWN

Countries

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United States

Central Contacts

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Siddharth Singh, MD

Role: CONTACT

858-246-2352

Jason Hou, MD

Role: CONTACT

713-798-8220

Facility Contacts

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Caroline Hwang, MD

Role: primary

Siddharth Singh, MD

Role: primary

858-246-2352

Gil Melmed, MD

Role: primary

310-423-4100

Ryan McConnell, MD

Role: primary

484-995-1640

Mark Gerich, MD

Role: primary

303-724-7244

Jill Gaidos, MD

Role: primary

203-785-4138

Mark Mattar, MD

Role: primary

202-444-4898

Jana Al Hashash, MD

Role: primary

904-953-0131

David Rubin, MD

Role: primary

773-702-2950

Corey Siegel, MD

Role: primary

603-650-5261

Mark Metwally, MD

Role: primary

518-831-1500

David Hudesman, MD

Role: primary

855-698-4232

Dana Lukin, MD

Role: primary

212-746-5077

Brandon Sprung, MD

Role: primary

Tauseef Ali, MD

Role: primary

Samir Shah, MD

Role: primary

401-274-4800

David Fudman, MD

Role: primary

214-645-6355

Jason Hou, MD

Role: primary

713-798-8220

Ann Flynn, MD

Role: primary

801-587-7678

References

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Singh S, Nguyen JD, Fudman DI, Gerich ME, Shah SA, Hudesman D, McConnell RA, Lukin DJ, Flynn AD, Hwang C, Sprung B, Gaidos JKJ, Mattar MC, Rubin DT, Hashash JG, Metwally M, Ali T, Ma C, Hoentjen F, Narula N, Bessissow T, Rosenfeld G, McCurdy JD, Ananthakrishnan AN, Cross RK, Rodriguez Gaytan JR, Gurrola ES, Patel S, Siegel CA, Melmed GY, Weaver SA, Power S, Zou G, Jairath V, Hou JK. Treat-to-target of endoscopic remission in patients with inflammatory bowel disease in symptomatic remission on advanced therapies (QUOTIENT): rationale, design and protocol for an open-label, multicentre, pragmatic, randomised controlled trial. BMJ Open Gastroenterol. 2025 Mar 31;12(1):e001615. doi: 10.1136/bmjgast-2024-001615.

Reference Type DERIVED
PMID: 40164445 (View on PubMed)

Other Identifiers

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RCT01519

Identifier Type: -

Identifier Source: org_study_id

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