Clinical trial NCT01239082: Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM)
Official title: CSP #577 - Colonoscopy vs. Fecal Immunochemical Testing in Reducing Mortality From Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2010-11-11
Enrollment: 50126
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: 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))
* Participation in a concurrent interventional study pertaining to the colon or rectum (including studies of colonoscopy or colorectal cancer screening. Waivers to this exclusion criteria can be requested and granted with the approval of the CONFIRM study co-chairs, the Cooperative Study Program and the leadership of the other study.
* Likely inability to track the individual over time (e.g. no permanent address at the time of screening for study entry)

Primary outcomes:
measure: The primary outcome is colorectal cancer mortality.
timeFrame: 10 years
Secondary outcomes:
measure: FIT Positive - If Colonoscopy is Warranted
timeFrame: 10 Years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix VA Health Care System, Phoenix, AZ
state: Arizona
city: Little Rock
country: United States
facility: Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
state: Arkansas
city: Fresno
country: United States
facility: VA Central California Health Care System, Fresno, CA
state: California
city: Loma Linda
country: United States
facility: VA Loma Linda Healthcare System, Loma Linda, CA
state: California
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System, San Diego, CA
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
city: Denver
country: United States
facility: VA Eastern Colorado Health Care System, Denver, CO
state: Colorado
city: West Haven
country: United States
facility: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
state: Connecticut
city: Washington
country: United States
facility: Washington DC VA Medical Center, Washington, DC
state: District of Columbia
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System, Gainesville, FL
state: Florida
city: Miami
country: United States
facility: Miami VA Healthcare System, Miami, FL
state: Florida
city: Orlando
country: United States
facility: Orlando VA Medical Center, Orlando, FL
state: Florida
city: Tampa
country: United States
facility: James A. Haley Veterans' Hospital, Tampa, FL
state: Florida
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur, GA
state: Georgia
city: Honolulu
country: United States
facility: VA Pacific Islands Health Care System, Honolulu, HI
state: Hawaii
city: Chicago
country: United States
facility: Jesse Brown VA Medical Center, Chicago, IL
state: Illinois
city: Indianapolis
country: United States
facility: Richard L. Roudebush VA Medical Center, Indianapolis, IN
state: Indiana
city: Louisville
country: United States
facility: Robley Rex VA Medical Center, Louisville, KY
state: Kentucky
city: Baltimore
country: United States
facility: Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
state: Maryland
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System, Ann Arbor, MI
state: Michigan
city: Detroit
country: United States
facility: John D. Dingell VA Medical Center, Detroit, MI
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City VA Medical Center, Kansas City, MO
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis VA Medical Center John Cochran Division, St. Louis, MO
state: Missouri
city: Manchester
country: United States
facility: Manchester VA Medical Center, Manchester, NH
state: New Hampshire
city: East Orange
country: United States
facility: East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ
state: New Jersey
city: Northport
country: United States
facility: Northport VA Medical Center, Northport, NY
state: New York
city: Durham
country: United States
facility: Durham VA Medical Center, Durham, NC
state: North Carolina
city: Salisbury
country: United States
facility: Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC
state: North Carolina
city: Cleveland
country: United States
facility: Louis Stokes VA Medical Center, Cleveland, OH
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma City VA Medical Center, Oklahoma City, OK
state: Oklahoma
city: Portland
country: United States
facility: VA Portland Health Care System, Portland, OR
state: Oregon
city: Philadelphia
country: United States
facility: Philadelphia MultiService Center, Philadelphia, PA
state: Pennsylvania
city: Providence
country: United States
facility: Providence VA Medical Center, Providence, RI
state: Rhode Island
city: Memphis
country: United States
facility: Memphis VA Medical Center, Memphis, TN
state: Tennessee
city: Dallas
country: United States
facility: VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center, Houston, TX
state: Texas
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City, UT
state: Utah
city: White River Junction
country: United States
facility: White River Junction VA Medical Center and Regional Office, White River Junction, VT
state: Vermont
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center, Richmond, VA
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound Health Care System Seattle Division, Seattle, WA
state: Washington
city: Clarksburg
country: United States
facility: Clarksburg Louis A. Johnson VA Medical Center, Clarksburg, WV
state: West Virginia
city: Madison
country: United States
facility: William S. Middleton Memorial Veterans Hospital, Madison, WI
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: VA Caribbean Healthcare System, San Juan, PR
Study officials:
affiliation: VA Puget Sound Health Care System Seattle Division, Seattle, WA
name: Jason A. Dominitz, MD MHS
role: STUDY_CHAIR
affiliation: White River Junction VA Medical Center, White River Junction, VT
name: Douglas J Robertson, MD MPH
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.