Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM)

NCT ID: NCT01239082

Last Updated: 2025-11-10

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

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

50126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-30

Study Completion Date

2028-12-01

Brief Summary

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Colorectal cancer (CRC) is currently the second most common cause of cancer death in the United States, and one of the most preventable cancers. It has been shown in several randomized controlled trials that screening using fecal occult blood testing (FOBT) reduces CRC mortality by 13-33%. While there is strong consensus amongst experts regarding the value of CRC screening, the best approach to screening is not clear. Of the widely recommended modalities, FOBT and colonoscopy are the most commonly used within the United States. FOBT is inexpensive, non-invasive, and its use as a screening tool is supported by the highest quality evidence (i.e. randomized controlled trials). Moreover, newer FOBT, such as fecal immunochemical tests or FITs, have advantages over conventional FOBT in terms of both test characteristics and ease of use that make them quite attractive as a population-based screening tool.

While colonoscopy is invasive and has higher up-front risks and costs than FOBT, it does afford the opportunity to directly assess the colonic mucosa and is widely believed to be the best test to detect colorectal cancer. In addition, colonoscopy allows for the detection and removal of colorectal adenomas -a well recognized colorectal cancer precursor. There is indirect evidence that suggests colonoscopy is effective in reducing colorectal cancer mortality, but to date, no large clinical trials have been completed to support this assumption. While colonoscopy use is increasing, data is emerging that colonoscopy may not be as effective as previously believed. Prior support for colonoscopy as a screening test relied upon effectiveness estimates that now appear to be overly optimistic. Given the invasive nature of colonoscopy, the associated small, but real risk of complications, and dramatically higher costs than other screening tests, it is especially important to determine the true comparative effectiveness of colonoscopy relative to other proven non-invasive options.

The investigators propose to perform a, large, simple, multicenter, randomized, parallel group trial directly comparing screening colonoscopy with annual FIT screening in average risk individuals. The hypothesis is that colonoscopy will be superior to FIT in the prevention of colorectal cancer mortality measured over 10 years. Individuals will be enrolled if they are currently eligible for CRC screening (e.g. no colonoscopy in the past 10 years and no FOBT in the past 1 year) and are between 50 and 75 years of age. The investigators will exclude individuals for whom colonoscopy is indicated (e.g. signs or symptoms of CRC, first degree family member with CRC, personal history of colorectal neoplasia or inflammatory bowel disease).

All participants will complete baseline demographic, medication, and lifestyle questionnaires (e.g. diet, non-steroidal anti-inflammatory use, frequency of exercise) prior to randomization in a 1:1 ratio to either screening colonoscopy or annual FIT screening (Figure 1). Those testing positive by FIT will undergo evaluation to determine appropriateness for colonoscopy. Screening will be performed in a manner consistent with the currently accepted standard of care in order to determine the comparative effectiveness of the two screening strategies. Participants will be surveyed annually to determine if they have undergone colonoscopy or been diagnosed with CRC.

The primary study endpoint will be CRC mortality within 10 years of enrollment. The secondary endpoints are (1) the incidence of CRC within 10 years of enrollment and (2) major complications of colonoscopy. Mortality will be determined through queries of the VA Vital Status File. Cause of death will be determined primarily using death certificates from the National Death Index-Plus database, augmented by adjudication of medical records for known CRC cases where CRC is not listed as a cause of death on the death certificate. The investigators postulate that screening colonoscopy will result in a 40% reduction in CRC mortality over 10 years relative to annual FIT screening. Using a log-rank test with a 2-sided test of significance, =0.05, a sample size of 50,000 participants will be required to test the primary hypothesis with 82% power, assuming a 1% annual rate of crossover from FIT to colonoscopy and a 0.5% annual rate of loss to follow-up. The planned study duration is 12.5 years with 2.5 years of recruitment and 10 years of follow-up for all enrolled participants.

Detailed Description

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Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Arm 1

Colonoscopy (one time screening)

Group Type OTHER

Colonoscopy

Intervention Type PROCEDURE

One time screening Colonoscopy to screen for colorectal cancer

Arm 2

FIT (annually)

Group Type OTHER

FIT

Intervention Type PROCEDURE

Annual FIT testing

Interventions

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Colonoscopy

One time screening Colonoscopy to screen for colorectal cancer

Intervention Type PROCEDURE

FIT

Annual FIT testing

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Male and female adults aged 50-75 years of age
* Veteran
* Able to provide informed consent

Exclusion Criteria

* Symptoms of lower gastrointestinal tract disease warranting colonoscopic evaluation, including:

* More than one episode of rectal bleeding within the past 6 months
* Documented iron deficiency anemia
* Significant documented unintentional weight loss (\>10% of baseline weight) over 6 months
* Family history of CRC in a first degree relative at any age
* Prior history of colonic disease including:

* Inflammatory bowel disease (e.g. ulcerative colitis or Crohn's disease)
* One or more colorectal neoplastic polyps (i.e. adenomas)
* Colorectal cancer
* Prior history of colonic resection
* Prior colonic examination, including:

* Colonoscopy within the past 9.5 years
* Sigmoidoscopy within the past 5 years
* Barium enema within the past 5 years
* CT colonography within the past 5 years
* gFOBT or FIT in the past 10 months
* Stool DNA test within the past 3 years
* Pregnancy
* Prisoner
* Significant comorbidity that would preclude benefit from screening or pose significant risk for the performance of colonoscopy (e.g. severe lung disease, end-stage renal disease, end-stage liver disease, severe heart failure, recent diagnosis of cancer (with the exception of non-melanoma skin cancer))
* Likely inability to track the individual over time (e.g. no permanent address at the time of screening for study entry)
Minimum Eligible Age

50 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jason A. Dominitz, MD MHS

Role: STUDY_CHAIR

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Douglas J Robertson, MD MPH

Role: STUDY_CHAIR

White River Junction VA Medical Center, White River Junction, VT

Locations

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Phoenix VA Health Care System, Phoenix, AZ

Phoenix, Arizona, United States

Site Status

Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR

Little Rock, Arkansas, United States

Site Status

VA Central California Health Care System, Fresno, CA

Fresno, California, United States

Site Status

VA Loma Linda Healthcare System, Loma Linda, CA

Loma Linda, California, United States

Site Status

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, United States

Site Status

VA San Diego Healthcare System, San Diego, CA

San Diego, California, United States

Site Status

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, United States

Site Status

VA Eastern Colorado Health Care System, Denver, CO

Denver, Colorado, United States

Site Status

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, United States

Site Status

Washington DC VA Medical Center, Washington, DC

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

Site Status

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, United States

Site Status

Miami VA Healthcare System, Miami, FL

Miami, Florida, United States

Site Status

Orlando VA Medical Center, Orlando, FL

Orlando, Florida, United States

Site Status

James A. Haley Veterans' Hospital, Tampa, FL

Tampa, Florida, United States

Site Status

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, United States

Site Status

VA Pacific Islands Health Care System, Honolulu, HI

Honolulu, Hawaii, United States

Site Status

Jesse Brown VA Medical Center, Chicago, IL

Chicago, Illinois, United States

Site Status

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, United States

Site Status

Robley Rex VA Medical Center, Louisville, KY

Louisville, Kentucky, United States

Site Status

Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Baltimore, Maryland, United States

Site Status

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, United States

Site Status

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, United States

Site Status

John D. Dingell VA Medical Center, Detroit, MI

Detroit, Michigan, United States

Site Status

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

Site Status

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, United States

Site Status

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

St Louis, Missouri, United States

Site Status

Manchester VA Medical Center, Manchester, NH

Manchester, New Hampshire, United States

Site Status

East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ

East Orange, New Jersey, United States

Site Status

Northport VA Medical Center, Northport, NY

Northport, New York, United States

Site Status

Durham VA Medical Center, Durham, NC

Durham, North Carolina, United States

Site Status

Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC

Salisbury, North Carolina, United States

Site Status

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, United States

Site Status

Oklahoma City VA Medical Center, Oklahoma City, OK

Oklahoma City, Oklahoma, United States

Site Status

VA Portland Health Care System, Portland, OR

Portland, Oregon, United States

Site Status

Philadelphia MultiService Center, Philadelphia, PA

Philadelphia, Pennsylvania, United States

Site Status

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, United States

Site Status

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, United States

Site Status

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, United States

Site Status

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Site Status

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, United States

Site Status

White River Junction VA Medical Center and Regional Office, White River Junction, VT

White River Junction, Vermont, United States

Site Status

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, United States

Site Status

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, United States

Site Status

Clarksburg Louis A. Johnson VA Medical Center, Clarksburg, WV

Clarksburg, West Virginia, United States

Site Status

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, United States

Site Status

VA Caribbean Healthcare System, San Juan, PR

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Dominitz JA, Robertson DJ, Ahnen DJ, Allison JE, Antonelli M, Boardman KD, Ciarleglio M, Del Curto BJ, Huang GD, Imperiale TF, Larson MF, Lieberman D, O'Connor T, O'Leary TJ, Peduzzi P, Provenzale D, Shaukat A, Sultan S, Voorhees A, Wallace R, Guarino PD. Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design. Am J Gastroenterol. 2017 Nov;112(11):1736-1746. doi: 10.1038/ajg.2017.286. Epub 2017 Oct 10.

Reference Type BACKGROUND
PMID: 29016565 (View on PubMed)

Robertson DJ, Dominitz JA, Beed A, Boardman KD, Del Curto BJ, Guarino PD, Imperiale TF, LaCasse A, Larson MF, Gupta S, Lieberman D, Planeta B, Shaukat A, Sultan S, Menees SB, Saini SD, Schoenfeld P, Goebel S, von Rosenvinge EC, Baffy G, Halasz I, Pedrosa MC, Kahng LS, Cassim R, Greer KB, Kinnard MF, Bhatt DB, Dunbar KB, Harford WV Jr, Mengshol JA, Olson JE, Patel SG, Antaki F, Fisher DA, Sullivan BA, Lenza C, Prajapati DN, Wong H, Beyth R, Lieb JG 2nd, Manlolo J, Ona FV, Cole RA, Khalaf N, Kahi CJ, Kohli DR, Rai T, Sharma P, Anastasiou J, Hagedorn C, Fernando RS, Jackson CS, Jamal MM, Lee RH, Merchant F, May FP, Pisegna JR, Omer E, Parajuli D, Said A, Nguyen TD, Tombazzi CR, Feldman PA, Jacob L, Koppelman RN, Lehenbauer KP, Desai DS, Madhoun MF, Tierney WM, Ho MQ, Hockman HJ, Lopez C, Carter Paulson E, Tobi M, Pinillos HL, Young M, Ho NC, Mascarenhas R, Promrat K, Mutha PR, Pandak WM Jr, Shah T, Schubert M, Pancotto FS, Gawron AJ, Underwood AE, Ho SB, Magno-Pagatzaurtundua P, Toro DH, Beymer CH, Kaz AM, Elwing J, Gill JA, Goldsmith SF, Yao MD, Protiva P, Pohl H, Kyriakides T; CONFIRM Study Group. Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial. JAMA Netw Open. 2023 Jul 3;6(7):e2321730. doi: 10.1001/jamanetworkopen.2023.21730.

Reference Type RESULT
PMID: 37432690 (View on PubMed)

Shaukat A, Kahi CJ, Burke CA, Rabeneck L, Sauer BG, Rex DK. ACG Clinical Guidelines: Colorectal Cancer Screening 2021. Am J Gastroenterol. 2021 Mar 1;116(3):458-479. doi: 10.14309/ajg.0000000000001122.

Reference Type DERIVED
PMID: 33657038 (View on PubMed)

Other Identifiers

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577

Identifier Type: -

Identifier Source: org_study_id