Screening for Stomach Diseases and Colorectal Neoplasms With the Fecal Testing

Screening for Stomach Diseases and Colorectal Neoplasms With the Fecal Testing: a Population-based Randomized Study

1. The abundant results from this trial will be helpful for assessing the feasibility of increasing stool sampling and shortening screening interval in population setting for lower and upper gastrointestinal tract lesions, their long-term effects, and the respective cost-effectiveness.
2. The study will evaluate the value of population-based screen and treatment for H. pylori infection when the HPSA is combined with the FIT.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Stomach Disease
• Intervention / Treatment: Other: FIT(Eiken OC-Sensor) One-year interval; Other: FIT(Eiken OC-Sensor) One-day sampling; Other: FIT(Eiken OC-Sensor) Two-year interval; Other: FIT(Eiken OC-Sensor) Two-day sampling; Other: HpSA (Firstep Helicobacter pylori Antigen Rapid Test); Other: FIT only

Detailed Description

Growing body of evidences have shown that fecal immunochemical test (FIT) outperform guaiac fecal occult blood test (gFOBT) in terms of sensitivity, neoplasm detection rate and public participation. Though direct outcome evidence is still lacking for FIT, it is anticipated to have higher colorectal cancer (CRC) mortality and incidence reduction compared with gFOBT. In Taiwan, nation-wide CRC screening program has been launched since the year of 2004 ,which provides biennial FIT screening for adults aged 50 to 69 years. Currently available data from the Bureau of Health Promotion has shown a significant stage-shift effect, an early indicator of screening effectiveness, by this screening program.

Nevertheless, the aforementioned advantages of FIT, missed neoplasms and interval cancer still exists under the current one-day stool sampling method with biennial screening interval, which might affect the effectiveness of overall screening program. Increase the number of stool samples or shortening of screening interval may be helpful for early detection of clinically significant neoplasms but it remains unclear whether such an approach may lower the screenee compliance or public participation. Moreover, its impact on the demand of confirmatory colonoscopy and cost-effectiveness of the whole screening program is still largely unknown and need to be further investigated.

In this study, we firstly aim to randomly allocate screening attendee to one of the following four arms: one-day sampling with annual screening, one-day sampling with biennial screening, two-day sampling with annual screening, and two-day sampling with biennial screening. Participation rate, positive rates of FIT, detection rate for neoplasms, positive predictive value, and long-term outcome including cancer incidence and mortality will be calculated and compared among four groups.

Secondly, in the Taiwanese population, which is a typical presentation of Asian populations, although the incidence of colorectal cancer is rapidly increasing, Helicobacter pylori-related upper gastrointestinal pathologies remain highly prevalent, which may imply that mass screening solely based on FIT could be insufficient as significant upper GI pathologies can be missed. Since the FIT does not predict upper GI pathologies, the adjunct of an「Helicobacter pylori stool-antigen test (HpSA) 」 may be a potential candidate to realize a pan-detecting assay based on stool samples in a population in which both lower and upper GI lesions are equally prevalent. Therefore, in the present study, we will also evaluate the value of simultaneous FIT and HpSA test in the community-based mass screening. We invited subjects in a randomized study to receive the FIT or the FIT plus HPSA. Those who are tested positive for HPSA will receive upper endoscopic examination and anti-H. pylori treatment. For the short-term indicators, we will evaluate the participation rate and diagnostic yield when the HPSA is added. For the long-term indicators, we will compare the incidence and mortality of gastric cancer as well as complicated peptic ulcers.

To summary, this study includes two randomized trials:

1. To make a comparison between one-day sampling with annual screening, one-day sampling with biennial screening, two-day sampling with annual screening, and two-day sampling with biennial screening using FIT;
2. To make a comparison between FIT plus HpSA and FIT alone for screening.

Finally, the cost-effectiveness analysis will be also conducted using previously established Markov model of CRC natural history and stomach diseases (such as dyspepsia, peptic ulcer disease, and gastric cancer) using the results ascertained from this trial. The primary outcomes were gastric cancer incidence and mortality rates as well as colorectal cancer incidence and mortality rates.

• Study Type: Interventional
• Enrollment (Actual): 99314
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 50 to 69 years average-risk subjects for FIT
• 50 to 69 years subjects for HpSA

Exclusion Criteria (for the FIT-based RCT):

• Subjects who are unwilling to participate
• Subjects ineligible for colonoscopy (for the one-day vs two day FIT screening)

Exclusion Criteria (for the FIT+HPSA vs. FIT-only RCT)

• Subjects with a history of total gastrectomy
• Pregnancy
• Subjects with severe illnesses
• Subjects with prior participation in the pilot program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: one-day sampling with one-year interval; FIT one-day sampling with one-year interval	Other: FIT(Eiken OC-Sensor) One-year interval; Screening with one-year interval; Other: FIT(Eiken OC-Sensor) One-day sampling; One-day sampling
Active Comparator: one-day sampling with two-year interval; FIT one-day sampling with two-year interval	Other: FIT(Eiken OC-Sensor) One-day sampling; One-day sampling; Other: FIT(Eiken OC-Sensor) Two-year interval; Screening with two-year interval
Experimental: two-day sampling with one-year interval; FIT two-day sampling with one-year interval	Other: FIT(Eiken OC-Sensor) One-year interval; Screening with one-year interval; Other: FIT(Eiken OC-Sensor) Two-day sampling; Collect two stool samples in two separate days
Experimental: two-day sampling with two-year interval; FIT two-day sampling with two-year interval	Other: FIT(Eiken OC-Sensor) Two-year interval; Screening with two-year interval; Other: FIT(Eiken OC-Sensor) Two-day sampling; Collect two stool samples in two separate days
Experimental: Hp stool antigen (HpSA)+FIT; HpSA for detection of upper gastrointestinal tract diseases and upper endoscopy for H. pylori carriers; HPSA combined with FIT	Other: FIT(Eiken OC-Sensor) One-day sampling; One-day sampling; Other: FIT(Eiken OC-Sensor) Two-year interval; Screening with two-year interval; Other: HpSA (Firstep Helicobacter pylori Antigen Rapid Test); HpSA for detection of upper gastrointestinal diseases; screen and treat for H. pylori infection. Upper endoscopy for H. pylori carriers. HPSA+FIT compared with FIT alone.
Active Comparator: FIT only; HpSA + FIT compared with FIT alone	Other: FIT(Eiken OC-Sensor) One-day sampling; One-day sampling; Other: FIT(Eiken OC-Sensor) Two-year interval; Screening with two-year interval; Other: FIT only; HPSA+FIT compared with FIT alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Stomach Cancer	Number of incident stomach cancer The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years
Mortality of Stomach Cancer	Number of stomach cancer death The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality of Colorectal Cancer	Number of colorectal cancer death The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years
Incidence of Colorectal Cancer	Number of incident colorectal cancer The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Helicobacter Pylori Eradication Rate	Subjects who received anti-H. pylori treatment. The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years
Confirmatory Examination Referral Rate	Subjects who received confirmatory examinations (colonoscopy or flexible sigmoidoscopy plus double contrast barium enema for lower gastrointestinal tract disease; esophagogastroduodenoscopy for upper gastrointestinal tract disease) /subjects with positive stool test (FIT or HpSA) The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years
Detection of Advanced Adenoma and Cancer	Number of Advanced Adenoma and Colorectal Cancer The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years
Participation Rate of HpSA + FIT or FIT Only	Number of participants from invitation population The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years
Detection of Non-advanced Adenoma	Number of non-advanced adenoma from study population The recruitment period of participants was from January 1, 2014 to September 27, 2018. Final follow-up occurred December 31, 2020. For outcome measurement, the average follow-up time of the study participants was 5.5 years.	5.5 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Ministry of Health and Welfare, Taiwan
• Investigators: Principal Investigator: Han-Mo Chiu, M.D., Ph.D., Department of Internal Medicine & Health Management Center; Principal Investigator: Yi-Chia Lee, M.D., Ph.D., National Taiwan University Hospital

Publications and helpful links

General Publications

• Lee YC, Chiang TH, Chiu HM, Wu MS, Yeh YP, Hsiu-Hsi Chen T; Collaborators of the Taiwan Community-Based Integrated Screening Group. Community-Based Gastric Cancer Screening Coupled With a National Colorectal Cancer Screening Program: Baseline Results. Gastroenterology. 2021 May;160(6):2159-2161.e4. doi: 10.1053/j.gastro.2021.01.008. Epub 2021 Jan 11. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 5, 2012
• First Submitted That Met QC Criteria: November 30, 2012
• First Posted (Estimated): December 4, 2012

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: iFOBT; one-day sample; two-day sample; Helicobacter pylori stool antigen
• Additional Relevant MeSH Terms: Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplasms; Colorectal Neoplasms; Stomach Diseases
• Other Study ID Numbers: 201205030RIB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No