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

NCT05230173 | Recruiting DMC

• 1 other identifier: RCT01519
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 22

Brief Summary

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.

Conditions

Ulcerative Colitis; Crohn Disease

Outcome Measures

Primary Outcomes (1)

• 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

  From randomization up to 104 weeks

Secondary Outcomes (5)

• Treatment failure as defined in the composite primary outcome

  Binary, 104 weeks

• Time to each individual component of the composite primary outcome

  From randomization up to 104 weeks

• Overall Quality of Life

  Continuous, until 104 weeks or Early Discontinuation

• Treatment Burden/Satisfaction

  Continuous, until 104 weeks or Early Discontinuation

• Overall Safety

  Continuous, until 104 weeks or Early Discontinuation

Study Arms (2)

Switching Targeted Immunomodulators Treatment

OTHER

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).

Other: Pragmatic

Continuing Index Targeted Immunomodulators Treatment

OTHER

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

Other: Pragmatic

Interventions

Pragmatic 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; Switching Targeted Immunomodulators Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or nonpregnant, nonlactating females, ≥ 18 years of age.
• An established diagnosis of CD or UC for at least 6 months based on standard clinical criteria, confirmed by the treating provider.
• 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.
• 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.
• 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:
• CD: PRO2 (2-item patient reported outcome) mean daily score of abdominal pain score ≤1 and stool frequency score ≤ 3; or
• UC: PRO2, with absence of rectal bleeding (rectal bleeding score = 0) and with stool frequency score ≤1.
• 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:
• 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
• CD: MRE or CTE showing moderately to severely active inflammation based on 1 of the following variables:
• Increased bowel wall thickness, or

You may not qualify if:

• Presence of ostomy or ileoanal pouches.
• 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.
• 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.
• Prior enrolment in the current study.
• Mild endoscopic disease activity, where treating providers would not consider switching TIM.

Sponsors & Collaborators

• University of California, San Diego: lead
• Baylor College of Medicine: collaborator
• Crohn's and Colitis Foundation: collaborator
• Western University: collaborator
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (22)

Hoag Hospital

Irvine, California, 92618, United States

RECRUITING

UC San Diego Health

La Jolla, California, 92037, United States

RECRUITING

Cedars-Sinai

Los Angeles, California, 90048, United States

RECRUITING

Sutter Health

Palo Alto, California, 94301, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

RECRUITING

University of Chicago Medicine

Chicago, Illinois, 60637, United States

RECRUITING

Dartmouth Hitchcock

Lebanon, New Hampshire, 03756, United States

RECRUITING

Saratoga Schenectady Gastroenterology Associates

Burnt Hills, New York, 12027, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Cornell University

New York, New York, 10021, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Hightower Clinical

Oklahoma City, Oklahoma, 73102, United States

NOT YET RECRUITING

Oregon Clinic

Portland, Oregon, 97220, United States

WITHDRAWN

Gastroenterology Associates

Providence, Rhode Island, 02904, United States

RECRUITING

GastroOne

Germantown, Tennessee, 38138, United States

WITHDRAWN

University of Texas Southwestern

Dallas, Texas, 75235, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

University of Utah Health

Salt Lake City, Utah, 84132, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22908, United States

WITHDRAWN

Related Publications (1)

• 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.

  PMID: 40164445 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease

Interventions

Pragmatic Clinical Trials as Topic

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Randomized Controlled Trials as Topic; Controlled Clinical Trials as Topic; Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Siddharth Singh, MD

  UC San Diego Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Siddharth Singh, MD

CONTACT

858-246-2352; sis040@health.ucsd.edu

Jason Hou, MD

CONTACT

713-798-8220; jkhou@bcm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: February 8, 2022
• Study Start: October 5, 2022
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 15, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)