Who can take part in the ASAC trial?
The trial is open for inclusion of patients above 18 years who are scheduled for curative treatment of colorectal cancer liver metastases. The patients are randomized to either acetylsalicylic acid (ASA) 160 mg daily or placebo one tablet daily for three years. Individuals cannot take part in the study if they regularly take aspirin, non-steroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen), corticosteroids, anti-coagulants (e.g. warfarin or heparin), or other medications that can increase bleeding risk. They can also not be included if they are at risk of developing side effects from aspirin (e.g. a stomach ulcer) or have an inherited bleeding disorder. Patients with severe kidney or heart failure or liver cirrhosis can also not participate.
What is a placebo?
A placebo is an «imitation» tablet. It looks like an ASA tablet but it doesn’t contain any active medicine. The ASAC trial uses a placebo so that we can make as clear an assessment as achievable about the effects of ASA. To make sure the results are as reliable as possible, neither the participants, nor the doctors, will know or be able to choose who is taking active medication and who is taking a placebo. This is called a double-blind trial.
Study treatment and unblinding
Participants who consent to participate in the ASAC trial are randomly assigned by a computer to take either ASA 160 mg or a placebo, which they will take once a day for up to three years or till disease recurrence. The start of treatment is usually four weeks after surgery. All participants have 50% chance of receiving ASA. In case of medical emergency, all doctors at Department of HPB surgery at Oslo University Hospital can find out which treatment a participant is taking. This is known as unblinding. Almost all clinical scenarios can be managed by assuming a trial participant is taking ASA 160 mg once a day and withholding the trial medication. We only expect unblinding to be necessary in rare clinical circumstances where knowledge of treatment allocation is essential to guide clinical management. In case of emergency unblinding, please contact: Oslo University Hospital, Tel: +47-23070000 or Study Nurses: Victoria Bringsjord (vicbri@ous-hf.no) or Gyda G Christiansen (gydchr@ous-hf.no) UNBLINDING CAN ONLY BE PERFORMED BY AN HPB-SURGEON ON CALL AT OSLO UNIVERSITY HOSPITAL AND SHOULD ONLY BE CONSIDERED WHERE KNOWLEDGE OF TREATMENT ALLOCATION IS ESSENTIAL TO GUIDE CLINICAL MANAGEMENT.
Taking the study medication
All included patients will receive study medication for one-year´s usage and take one tablet once a day, every day for up to three years. Tablets should be swallowed whole with water, preferably with a meal. It is very important that the tablets are taken every day. If you forget to take a tablet, do not take additional tablets to catch-up. If you are going to receive a surgical or dental treatment, please inform that you are participating in the ASAC trial and may be on ASA 160 mg. You can in case of treatment stop taking the tablets for 5 days. Please register how many days the tablets are not taken.
Other medications
It is very important that trial participants do not take other medications that contain ASA whilst they are taking part in the study. It is also important that participants do not take ASA bought over the counter from a pharmacy or shop. This may be unsafe and significantly increases the risk of side effects, like ulcer. Your study doctor or GP will be able to advise you on this. The following medications should not be taken at the same time as long as you are on study medication. If you are unsure whether you can take a medication please discuss with your study doctor or GP. • Any medications that contain acetylsalicylic acid, which include: Albyl-E, Aspirin, Asasantin, Acetylsalisylsyre, Diprasorin, Paralen, Globoid. • Anti-coagulation medication, which includes: Marevan, Warfarin, Fragmin, Klexane, Heparin. • Anti-platelet medication, which include: Clopidogrel, Persantin, Dipyridamole, Prasugrel, Ticagrelor, Abciximab, Eptifibatide, Epoprostenol, Fondaparinaux • Other medications: Corticosteroids, Methotrexate, digoxin, lithium, valproate, phenytoin, Sulfonureids
Quality of Life assessment
All trial participants will fill-out Quality of Life (QoL) questionnaires (SF-36 and EQ-5D) at time of inclusion and at each follow-up. We are interested in determining the effect of Aspirin 160 mg on Health-related Quality of Life outcome measures. The participants can fill out the QoL questionnaires either on-line by logging into ViewdocMe, written, or by-proxy by contacting an ASAC study nurse. The QoL forms take approximately 10 minutes to fill out.
How often are the follow-ups?
All participants are followed up according to the National Guidelines for patients with Colorectal Liver Metastases. All patients are controlled with a CT scan of the chest and abdomen and blood level of tumour antigen CEA. In Norway this is performed every 4 months the first year and further every 6 months. In Sweden the patients are controlled every 6 months. All controls are performed at the local hospitals, but the results are submitted to the ASAC trial centre to be registered in the electronic CRF. Once a year (every 12 months) the participants will be controlled at the ASAC trial centre and also receive next years study medication.
What happens at disease recurrence?
If a study participant is diagnosed with disease recurrence within the trial period of 3 years, either as lung metastases, liver metastases, or local recurrence in the abdomen, the ASAC trial centre will be informed promptly and the study medications will be discontinued. The participant will however be treated according to the National Guidelines. We will follow-up all participants for the whole study period (3 years) with registration of QoL.