The ASAC trial is a Scandinavian, multi-center, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose acetylsalicylic acid (ASA) can improve disease free survival in patients treated with resection for colorectal cancer liver metastases (CRCLM).

Several studies have shown beneficial effect of ASA on primary prevention of CRC and the investigators group and others have shown a potential association of ASA also taken after the diagnosis on CRC survival in registry-based studies (secondary prevention). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo for a period of 3 years or till disease recurrence. The patients will be treated and followed up according to standard of care and the National Guidelines.

The ASAC trial will be the first clinical interventional trial to assess the beneficial role of ASA in recurrence of CRC liver metastases and survival. ASA is an inexpensive, well tolerated, and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRC liver metastases if the study shows a beneficial effect. This trial will also investigate the effect of ASA as adjuvant treatment on Health-related Quality of Life and the cost-effectiveness.

Inclusion Criteria:

• First time CRCLM (synchronous or metachronous).
• Recurrence of CRCLM (not previously included in this trial).
• In synchronous CRCLM and "Liver first" approach, the primary tumor must be resected within 6 weeks after the liver
• Macroscopic (surgical) free resection margins (R0 or R1 resection).
• Must be ambulatory with a performance status Eastern Cooperative Oncology Group (ECOG) 0-2.
• Must be at least 18 years of age.
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonization - Good Clinical Practice (ICH GCP), and national/local regulations.

Exclusion Criteria:

• Concomitant use of ASA or other anticoagulants or platelet inhibitors such as warfarin or clopidogrel.
• Ongoing regular use of corticosteroids or NSAIDs.
• Inherited or acquired coagulopathy (haemophilia).
• Blood platelets (thrombocytes) < 100 x 10^9/L.
• Severe heart failure (classified as New York Heart Association (NYHA) class >III)
• Severe kidney failure >Stage 3b
• CRCLM previously treated with radiofrequency or microwave ablation technique
• Pregnancy or breastfeeding. For women in childbearing age there will be pregnancy test at monthly intervals (urine human chorionic gonadotropin (HCG) pregnancy tests (for home testing) will be given to the patients for monthly tests and the patient will self-report the results at each control). Furthermore, highly effective contraceptives will be required.
• Childbearing potential without proper contraceptive measures such as oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device to avoid pregnancy for the entire study period.
• Liver cirrhosis with a Child-Pugh score >B7.
• Alcoholism.
• Contraindication listed on the Summary of Product Characteristics (SmPC) of Trombyl: Hypersensitivity/allergies to ASA, Thrombocytopenia, Previous severe gastrointestinal haemorrhage/peptic ulcer due to ASA/NSAID, Active peptic ulcer, Haemophilia, Liver cirrhosis, Severe congestive heart failure.
• Need to use concomitant medications contraindicated according to SmPC of Trombyl.

Eligible patients will be allocated in a 1:1 ratio using a computer randomization procedure stratified by centre. The randomization will be blocked within each stratum.