The Northern-European Initiative on Colorectal Cancer

Study Overview
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Brief Summary
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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.

Official Title
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NordICC The Northern-European Initiative on Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Procedure: Colonoscopy


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colonoscopy screening<br>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<br>* Once-only colonoscopy screening<br>|
| No Intervention: Control<br>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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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) |