The Northern-European Initiative on Colorectal Cancer (NordICC)

NordICC The Northern-European Initiative on Colorectal Cancer

Colorectal cancer (CRC) is a major burden in western countries. The disease develops from precursor lesions during a long time-interval. Colonoscopy can detect and remove CRC precursor lesions and may thus be effective for CRC prevention. Many national and international health organisations demand evidence from randomised trials to reduce incidence or mortality of the target disease before advocating population-wide cancer screening. However, while colonoscopy screening for the prevention of colorectal cancer is established in the United States and several European countries, no randomised trials exist to quantify the possible benefit of colonoscopy screening. NordICC is a randomised trial investigating the effect of colonoscopy on CRC incidence and mortality.

NordICC is a multicentre, randomised trial in Nordic countries, the Netherlands and Poland. A minimum of 66 000 individuals, age 55-64 years, are drawn randomly from the population registries in the participating countries. 22 000 are invited for once-only colonoscopy (2:1 randomisation). Expected work-load with 50% compliance will be 11,000 colonoscopies. At the screening examination, all detected lesions are biopsied and removed whenever possible. The remaining 44 000 individuals (control group) are not offered any screening examination (care as usual).The primary study aims are CRC incidence and CRC mortality after 15 years of follow-up, with an interim analysis after 10 years of follow-up. In an intention-to-treat approach, a risk reduction of CRC mortality of 25% in the colonoscopy screening group compared to the control group is expected after 10 years follow-up, estimating 50% compliance in the screening group.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Colonoscopy

• Study Type: Interventional
• Enrollment (Actual): 95000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iceland
  • Reykjavik, Iceland
    • Landspitali University Hospital
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus University Medical Center
• Norway
  • Oslo, Norway
    • Oslo University Hospital
• Poland
  • Warsaw, Poland, 02-781
    • Maria Sklodowska-Curie Memorial Cancer Centre
• Sweden
  • Stockholm, Sweden
    • Karolinska Institute
• United States
  • Massachusetts
    • Boston, Massachusetts, United States
      • Harvard School of Public Health
  • New York
    • New York, New York, United States
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• This study is a population-based randomised controlled trial, with randomisation of individuals age 55-64 years living in the screening areas directly from the Population Registries to either screening group or control group. Eligible persons with the same home address will be randomised to the same group (household randomisation).

Exclusion Criteria:

• Individuals with previous colorectal surgery (resections, enterostomies)
• Individuals in need of long-lasting attention and nursing services (somatic or psychosocial, mental retardation).
• On-going cytotoxic treatment or radiotherapy for malignant disease
• Severe chronic (longer than trial duration) cardiac (NYHA III-IV)or lung disease
• Lifelong anticoagulant therapy with Warfarin
• A coronary event requiring hospitalization during the last 3 months
• A cerebrovascular event during the last 3 months
• Resident abroad
• Return of unopened letter of invitation and/or reminder (address unknown)
• Message from neighbour/family/post office on death of screenee (not updated in Population Registry)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colonoscopy screening; One-time colonoscopy is the screening tool used in this trial. All individuals in the screening group will be offered a full colonoscopy. At colonoscopy, all detected CRC precursor lesions will be removed, whenever possible.	Procedure: Colonoscopy; Once-only colonoscopy screening
No Intervention: Control; The control group will not be offered any screening or intervention within the trial, but follow usual care in the participating countries. Individuals assigned to the control group will not be informed about their status as controls in the trial. This approach facilitates a truly population-based study, which will be used to estimate the effect of the screening intervention in the general population, mimicking national CRC screening programs. All ethics committees at the participating centres have approved the study protocol before recruiting individuals to the trial. In Sweden, the national ethics committee particularly reviewed the non-information of the control group and found it ethically acceptable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of the screening group vs. the control group in an intention-to-treat model after 15 years of follow-up with regard to CRC mortality and CRC incidence	15 years after screening (interim analysis after 10 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
CRC mortality and CRC incidence of screening attendees compared to the control group and non-attendees	15 years after screening (interim analysis after 10 years)
Mortality from all causes	15 years after screening (interim analysis after 10 years)

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Memorial Sloan Kettering Cancer Center; Karolinska Institutet; Erasmus Medical Center; Harvard School of Public Health (HSPH); Landspitali University Hospital; Uppsala University Hospital; Maria Sklodowska-Curie National Research Institute of Oncology
• Investigators: Study Director: Hans-Olov Adami, MD PhD, Harvard School of Public Health, Boston, USA; Principal Investigator: Michael Bretthauer, MD PhD, Oslo University Hospital; Principal Investigator: Michal Filip Kaminski, MD PhD, Marie Cure Sklodowska Cancer Center

Publications and helpful links

General Publications

• 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.
• Bretthauer M, Loberg M, Wieszczy P, Kalager M, Emilsson L, Garborg K, Rupinski M, Dekker E, Spaander M, Bugajski M, Holme O, Zauber AG, Pilonis ND, Mroz A, Kuipers EJ, Shi J, Hernan MA, Adami HO, Regula J, Hoff G, Kaminski MF; NordICC Study Group. Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death. N Engl J Med. 2022 Oct 27;387(17):1547-1556. doi: 10.1056/NEJMoa2208375. Epub 2022 Oct 9.
• Bretthauer M, Kaminski MF, Loberg M, Zauber AG, Regula J, Kuipers EJ, Hernan MA, McFadden E, Sunde A, Kalager M, Dekker E, Lansdorp-Vogelaar I, Garborg K, Rupinski M, Spaander MC, Bugajski M, Hoie O, Stefansson T, Hoff G, Adami HO; Nordic-European Initiative on Colorectal Cancer (NordICC) Study Group. Population-Based Colonoscopy Screening for Colorectal Cancer: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):894-902. doi: 10.1001/jamainternmed.2016.0960.
• Pisera M, Kaminski MF, Kraszewska E, Rupinski M, Regula J. Reinvitation to screening colonoscopy: a randomized-controlled trial of reminding letter and invitation to educational meeting on attendance in nonresponders to initial invitation to screening colonoscopy (REINVITE). Eur J Gastroenterol Hepatol. 2016 May;28(5):538-42. doi: 10.1097/MEG.0000000000000578.
• Kaminski MF, Bretthauer M, Zauber AG, Kuipers EJ, Adami HO, van Ballegooijen M, Regula J, van Leerdam M, Stefansson T, Pahlman L, Dekker E, Hernan MA, Garborg K, Hoff G. The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer. Endoscopy. 2012 Jul;44(7):695-702. doi: 10.1055/s-0032-1306895. Epub 2012 Jun 21.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): July 1, 2036

Study Registration Dates

• First Submitted: April 17, 2009
• First Submitted That Met QC Criteria: April 17, 2009
• First Posted (Estimate): April 20, 2009

Study Record Updates

• Last Update Posted (Actual): June 19, 2017
• Last Update Submitted That Met QC Criteria: June 16, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: NordICC