Clinical trial NCT00119912: NORCCAP: Norwegian Colorectal Cancer Prevention Trial
Official title: Norwegian Colorectal Cancer Prevention Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Adenoma
Keywords: screening
flexible sigmoidoscopy
fecal occult blood
cancer
colon
rectum
Lead sponsor: Norwegian Department of Health and Social Affairs
Sponsor class: OTHER_GOV
Collaborators: name: Norwegian Cancer Society
First posted: 2005-07-14
Enrollment: 100000
Sex: ALL
Minimum age (years): 50
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to see if screening with flexible sigmoidoscopy (a flexible viewing tube) may reduce large bowel cancer and cancer deaths. The researchers also want to see if the addition of screening for occult blood in stools may contribute further to this aim. Additionally, the researchers also want to see to which extent (and in which direction) the study may influence overall endoscopic activity in the general population in the screening area and in areas where controlled screening is not established.

Detailed description: Although flexible sigmoidoscopy (FS) as a screening tool has a much higher test sensitivity than fecal occult blood tests (FOBT) for colorectal cancer and high-risk adenomas, randomised trials with long-term follow-up are missing. The primary aim is to evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions (polypectomy of adenomatous polyps)

Secondary aims:

1. Evaluation of cost/effectiveness of screening for CRC and significant, benign lesions using flex-sig only compared to flex-sig in combination with faecal tests
2. To evaluate to which extent (and in which direction) the study may influence overall endoscopic activity in the general population in the screening areas and in areas where controlled screening is not established
3. Determine the prevalence of known types familial CRC in a general population and try to define other groups with intermediate increased risk
4. Clarify possible psychosocial effects of endoscopic screening and how it may influence lifestyle and lifestyle related morbidity and overall mortality

Population:

21,000 men and women, aged 50-64 years, living in the city of Oslo or the county of Telemark are drawn by randomisation (approx. 1:5) from the population registry and invited to have a flexible sigmoidoscopy examination. The control group constitutes 79,000 individuals. Those invited for flexible sigmoidoscopy are further randomised (1:1) to bring or not to bring 3 successive stool samples for FOBT on attendance for FS.

Method:

This is a once-only screening concept with bowel cleansing being limited to a 240 ml Sorbitol enema given on attendance. The threshold for work-up colonoscopy is low as a positive screening test is defined as any polyp \>9mm, any histologically verified adenoma irrespective of size and a positive FOBT. The screening phase is limited to the period January 1999- January 2002 and the first follow-up results will not be reported until all entries have passed the 5-year mark (i.e. in early 2007).

Eligibility criteria: Inclusion Criteria:

* Men and women
* Living in Oslo or Telemark
* Age 50-64 years

Exclusion Criteria:

* Patients with previous open colorectal surgery (resections, enterostomies)
* Individuals in need of long lasting attention and nursing services (somatic or psychosocial reasons, mental retardation)
* On-going cytotoxic treatment or radiotherapy for malignant disease
* Severe chronic cardiac or lung disease (NYHA III-IV)
* Patients with heart valve replacement on life long anticoagulant therapy
* A coronary event during the last 3 months if having lead to hospitalisation
* Cerebrovascular accident during the last 3 months
* Resident abroad

Primary outcomes:
measure: 1. Evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions (polypectomy of adenomatous polyps).First evaluation after 5 years.
timeFrame: Evaluations in 2007 (published),2012,2017
Secondary outcomes:
measure: 1. Determine the prevalence of known types familial CRC in a general population and try to define other groups with intermediate increased risk. Results "in press" 2005.
timeFrame: Evaluated in 2005 (published)
measure: 2. Clarify possible psychosocial effects of endoscopic screening and how it may influence lifestyle and lifestyle related morbidity and overall mortality. Evaluation in 2005.
timeFrame: Evaluated in 2005 (published)
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Institute of Population-based Cancer Research
Study officials:
affiliation: Institute of Population-based Cancer Research
name: Giske Ursin, M.D.
role: STUDY_CHAIR
References:
citation: Hoff G, Grotmol T, Skovlund E, Bretthauer M; Norwegian Colorectal Cancer Prevention Study Group. Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial. BMJ. 2009 May 29;338:b1846. doi: 10.1136/bmj.b1846.
citation: Holme O, Bretthauer M, Eide TJ, Loberg EM, Grzyb K, Loberg M, Kalager M, Adami HO, Kjellevold O, Hoff G. Long-term risk of colorectal cancer in individuals with serrated polyps. Gut. 2015 Jun;64(6):929-36. doi: 10.1136/gutjnl-2014-307793. Epub 2014 Nov 16.
citation: Berstad P, Loberg M, Larsen IK, Kalager M, Holme O, Botteri E, Bretthauer M, Hoff G. Long-term lifestyle changes after colorectal cancer screening: randomised controlled trial. Gut. 2015 Aug;64(8):1268-76. doi: 10.1136/gutjnl-2014-307376. Epub 2014 Sep 2.
citation: Holme O, Loberg M, Kalager M, Bretthauer M, Hernan MA, Aas E, Eide TJ, Skovlund E, Schneede J, Tveit KM, Hoff G. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA. 2014 Aug 13;312(6):606-15. doi: 10.1001/jama.2014.8266.
citation: Larsen IK, Grotmol T, Almendingen K, Hoff G. Impact of colorectal cancer screening on future lifestyle choices: a three-year randomized controlled trial. Clin Gastroenterol Hepatol. 2007 Apr;5(4):477-83. doi: 10.1016/j.cgh.2006.12.011. Epub 2007 Mar 23.
citation: Larsen IK, Grotmol T, Almendingen K, Hoff G. Lifestyle as a predictor for colonic neoplasia in asymptomatic individuals. BMC Gastroenterol. 2006 Jan 13;6:5. doi: 10.1186/1471-230X-6-5.
citation: Larsen IK, Grotmol T, Almendingen K, Hoff G. Lifestyle characteristics among participants in a Norwegian colorectal cancer screening trial. Eur J Cancer Prev. 2006 Feb;15(1):10-9. doi: 10.1097/01.cej.0000186636.27496.bb.
citation: Stormorken AT, Hoff G, Norstein J, Bowitz-Lothe IM, Hanslien E, Grindedal E, Moller P. Estimated prevalence of hereditary cancers and the need for surveillance in a Norwegian county, Telemark. Scand J Gastroenterol. 2006 Jan;41(1):71-9. doi: 10.1080/00365520510023891.
citation: Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G. Biopsy of colorectal polyps is not adequate for grading of neoplasia. Endoscopy. 2005 Dec;37(12):1193-7. doi: 10.1055/s-2005-921031.
citation: Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G. Lifestyle-related risk factors and chemoprevention for colorectal neoplasia: experience from the large-scale NORCCAP screening trial. Eur J Cancer Prev. 2005 Aug;14(4):373-9. doi: 10.1097/00008469-200508000-00010.
citation: Skovlund E, Bretthauer M, Grotmol T, Larsen IK, Hoff G. Sensitivity of pain rating scales in an endoscopy trial. Clin J Pain. 2005 Jul-Aug;21(4):292-6. doi: 10.1097/01.ajp.0000110636.14355.3e.
citation: Hoff G, Grotmol T, Thiis-Evensen E, Bretthauer M, Gondal G, Vatn MH. Testing for faecal calprotectin (PhiCal) in the Norwegian Colorectal Cancer Prevention trial on flexible sigmoidoscopy screening: comparison with an immunochemical test for occult blood (FlexSure OBT). Gut. 2004 Sep;53(9):1329-33. doi: 10.1136/gut.2004.039032.
citation: Bretthauer M, Skovlund E, Grotmol T, Thiis-Evensen E, Gondal G, Huppertz-Hauss G, Efskind P, Hofstad B, Thorp Holmsen S, Eide TJ, Hoff G. Inter-endoscopist variation in polyp and neoplasia pick-up rates in flexible sigmoidoscopy screening for colorectal cancer. Scand J Gastroenterol. 2003 Dec;38(12):1268-74. doi: 10.1080/00365520310006513.
citation: Bretthauer M, Hoff GS, Thiis-Evensen E, Huppertz-Hauss G, Skovlund E. Air and carbon dioxide volumes insufflated during colonoscopy. Gastrointest Endosc. 2003 Aug;58(2):203-6. doi: 10.1067/mge.2003.340.
citation: Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G. The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years. Scand J Gastroenterol. 2003 Jun;38(6):635-42. doi: 10.1080/00365520310003002.
citation: Bretthauer M, Jorgensen A, Kristiansen BE, Hofstad B, Hoff G. Quality control in colorectal cancer screening: systematic microbiological investigation of endoscopes used in the NORCCAP (Norwegian Colorectal Cancer Prevention) trial. BMC Gastroenterol. 2003 Jun 13;3:15. doi: 10.1186/1471-230X-3-15.
citation: Bretthauer M, Hoff G. The use of CO2 in colonoscopy. Gastrointest Endosc. 2003 Mar;57(3):436-7; author reply 437-8. doi: 10.1067/mge.2003.108. No abstract available.
citation: Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G. Grading of distal colorectal adenomas as predictors for proximal colonic neoplasia and choice of endoscope in population screening: experience from the Norwegian Colorectal Cancer Prevention study (NORCCAP). Gut. 2003 Mar;52(3):398-403. doi: 10.1136/gut.52.3.398.
citation: Bretthauer M, Hoff G, Thiis-Evensen E, Grotmol T, Holmsen ST, Moritz V, Skovlund E. Carbon dioxide insufflation reduces discomfort due to flexible sigmoidoscopy in colorectal cancer screening. Scand J Gastroenterol. 2002 Sep;37(9):1103-7. doi: 10.1080/003655202320378329.
citation: Bretthauer M, Hoff G, Thiis-Evensen E, Grotmol T, Larsen IK, Kjellevold O, Skovlund E. Use of a disposable sheath system for flexible sigmoidoscopy in decentralized colorectal cancer screening. Endoscopy. 2002 Oct;34(10):814-8. doi: 10.1055/s-2002-34273.
citation: Larsen IK, Grotmol T, Bretthauer M, Gondal G, Huppertz-Hauss G, Hofstad B, Efskind P, Jorgensen A, Hoff G. Continuous evaluation of patient satisfaction in endoscopy centres. Scand J Gastroenterol. 2002 Jul;37(7):850-5.
citation: Bretthauer M, Gondal G, Larsen K, Carlsen E, Eide TJ, Grotmol T, Skovlund E, Tveit KM, Vatn MH, Hoff G. Design, organization and management of a controlled population screening study for detection of colorectal neoplasia: attendance rates in the NORCCAP study (Norwegian Colorectal Cancer Prevention). Scand J Gastroenterol. 2002 May;37(5):568-73. doi: 10.1080/00365520252903125.
citation: Bretthauer M, Thiis-Evensen E, Huppertz-Hauss G, Gisselsson L, Grotmol T, Skovlund E, Hoff G. NORCCAP (Norwegian colorectal cancer prevention): a randomised trial to assess the safety and efficacy of carbon dioxide versus air insufflation in colonoscopy. Gut. 2002 May;50(5):604-7. doi: 10.1136/gut.50.5.604.
citation: Jodal HC, Loberg M, Holme O, Adami HO, Bretthauer M, Emilsson L, Ransohoff DF, Hoff G, Kalager M. Mortality From Postscreening (Interval) Colorectal Cancers Is Comparable to That From Cancer in Unscreened Patients-A Randomized Sigmoidoscopy Trial. Gastroenterology. 2018 Dec;155(6):1787-1794.e3. doi: 10.1053/j.gastro.2018.08.035. Epub 2018 Aug 27.
citation: Holme O, Loberg M, Kalager M, Bretthauer M, Hernan MA, Aas E, Eide TJ, Skovlund E, Lekven J, Schneede J, Tveit KM, Vatn M, Ursin G, Hoff G; NORCCAP Study Groupdagger. Long-Term Effectiveness of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality in Women and Men: A Randomized Trial. Ann Intern Med. 2018 Jun 5;168(11):775-782. doi: 10.7326/M17-1441. Epub 2018 Apr 24.
citation: Berstad P, Botteri E, Larsen IK, Loberg M, Kalager M, Holme O, Bretthauer M, Hoff G. Lifestyle changes at middle age and mortality: a population-based prospective cohort study. J Epidemiol Community Health. 2017 Jan;71(1):59-66. doi: 10.1136/jech-2015-206760. Epub 2016 Jun 16.
citation: Swanson SA, Holme O, Loberg M, Kalager M, Bretthauer M, Hoff G, Aas E, Hernan MA. Bounding the per-protocol effect in randomized trials: an application to colorectal cancer screening. Trials. 2015 Nov 30;16:541. doi: 10.1186/s13063-015-1056-8.
citation: Riedel BM, Molloy AM, Meyer K, Fredriksen A, Ulvik A, Schneede J, Nexo E, Hoff G, Ueland PM. Transcobalamin polymorphism 67A->G, but not 776C->G, affects serum holotranscobalamin in a cohort of healthy middle-aged men and women. J Nutr. 2011 Oct;141(10):1784-90. doi: 10.3945/jn.111.141960. Epub 2011 Aug 24.
citation: Hoff G, Bretthauer M. Appointments timed in proximity to annual milestones and compliance with screening: randomised controlled trial. BMJ. 2008 Dec 17;337:a2794. doi: 10.1136/bmj.a2794.