ULTRA-high-risk Surveillance to Avoid Future Events: the ULTRA-SAFE Trial

NCT07378930 | Not Yet Recruiting DMC

• 1 other identifier: 202511135RINA
• Study Type: interventional
• Target: 940
• Locations: 0 countries
• Sites: N/A

Brief Summary

The ULTRA-SAFE clinical trial is a prospective, randomized study designed to address the limitations of current "one-size-fits-all" colorectal cancer surveillance guidelines. While international standards recommend a three-year follow-up colonoscopy for all high-risk patients, data suggests that those with multiple advanced adenomas face a significantly higher recurrence risk (20%) compared to those with only low-risk adenomas (9%). To provide more personalized care, the trial compares a Standard Arm (colonoscopy at year three) against a FIT Arm, where participants undergo annual fecal immunochemical testing in years one and two. A positive FIT triggers an earlier colonoscopy, with the goal of reducing the 3-year prevalence of metachronous advanced colorectal neoplasms (meta-ACRN) from 20% to approximately 12.7%. The study has enrolled roughly 940 participants to statistically validate whether this early screening intervention can effectively prevent future malignant events in ultra-high-risk populations.

Conditions

Colorectal Cancer Prevention; Surveillance Colonoscopy; Colorectal Neoplasms

Keywords

Colonoscopy surveillance; Colorectal cancer prevention; Post-polypectomy surveillance; Fecal immunochemical test

Outcome Measures

Primary Outcomes (1)

• 3-year incidence of metachronous ACRN

  The incidence of metachronous advanced colorectal neoplasm (ACRN: adenoma larger than 1cm OR with villous components OR with high-grade dysplasia OR colorectal cancer) at third-year surveillance colonoscopy in both arms

  three years after recuitment

Secondary Outcomes (2)

• Overall incidence of metachronous ACRN

  3 years after recruitment

• Overall incidence of metachronous colorectal cancer

  three years after recuitment

Study Arms (2)

Standard care arm

NO INTERVENTION

Surveillance colonoscopy performed at third year after initial colonoscopy

FIT arm

EXPERIMENTAL

Intervention: Early triage using Fecal immunochemical test Detailed: Participants in this group will undergo Fecal Immunochemical Testing (FIT) in the first and second years (FIT 1 \& 2) following their initial colonoscopy. If FIT 1 is positive, a colonoscopy will be scheduled within three months; regardless of those findings, a surveillance colonoscopy is still required in the third year. If FIT 1 is negative, the patient proceeds to FIT 2 in the second year. A positive FIT 2 likewise triggers a colonoscopy within three months, and a third-year surveillance colonoscopy remains mandatory unless the FIT 2-triggered colonoscopy occurs between 2.5 and 3.5 years after the initial procedure, in which case it fulfills the third-year requirement. If both FIT 1 and FIT 2 are negative, the participant will undergo their scheduled surveillance colonoscopy in the third year.

Diagnostic Test: Early triage using Fecal immunochemical test

Interventions

Early triage using Fecal immunochemical test DIAGNOSTIC_TEST

Fecal immunochemical test would be provided at first and second year after initial colonoscopy in FIT arm. Those with positive results would be arranged with early surveillance colonoscopy

FIT arm

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Adults aged 40 to 75 years.
• Initial Colonoscopy Findings: Detection and removal of at least two advanced adenomas during the baseline colonoscopy.
• Adherence: Willingness to comply with the assigned screening protocol, including fecal immunochemical testing (FIT) and follow-up colonoscopies

You may not qualify if:

• Age: Individuals younger than 40 or older than 75 years.
• High-Risk Predispositions: Patients with inflammatory bowel disease (IBD), Familial Adenomatous Polyposis (FAP), or a documented hereditary colorectal cancer syndrome (e.g., Lynch syndrome).
• Cancer History: A history of colorectal cancer (excluding carcinoma in situ).
• Contraindications: Patients for whom polypectomy is clinically inappropriate or unsafe.
• Adenoma Count/Type: Failure to meet the requirement of at least two advanced adenomas during the initial colonoscopy.
• Extensive Low-Risk Lesions: Presence of more than ten low-risk adenomas.
• Pregnancy: Currently pregnant individuals.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Wei-Yuan Chang, MS

CONTACT

+886-917-223-272; wychang1005@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: National Taiwan University Hospital

Model Details: The trial compares a Standard Arm, which receives routine follow-up colonoscopy at year three, against an Early Screening Group (FIT Arm). In the FIT Arm, participants undergo FIT at years one and two, triggering an earlier colonoscopy if positive. Based on assumptions regarding FIT sensitivity and false-positive rates, the intervention was predicted to reduce the 3-year prevalence of meta-ACRN. The primary endpoint is comparing the recurrence rate of meta-ACRN detected during the third-year surveillance colonoscopy between the two groups

Study Record Dates

• First Submitted: January 23, 2026
• First Posted: January 30, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): May 1, 2031
• Last Updated: January 30, 2026

Record last verified: 2026-01