EMT2 – A double-blind randomised controlled trial of the omega-3 fatty acid EPA in patients undergoing liver surgery for colorectal cancer liver metastasis

EPA CAPSULES USED IN EMT2 RECEIVE A LICENCE FOR USE FOR PREVENTION OF HEART DISEASE IN THE UK
Update JULY 2021

The EPA capsules used in the EMT2 trial have now received approval from the MHRA (the drugs approvals agency in the UK) for use for prevention of cardiovascular (heart) disease in people with risk factors for heart disease (the medicine is called Vazkepa). As part of the licensing process, the MHRA wanted the Patient Information Leaflet to explicitly mention that the capsule coating contains small amounts of a substance called soya lecithin and that people with a known soya or peanut allergy should avoid the capsules

As a result of this new information the EMT2 trial team have now changed the trial patient information sheet to make sure that anyone with a known soya or peanut allergy, or a rare hereditary condition called hereditary fructose intolerance, does not join the trial. Please note that the capsules used in the trial have not changed and have always contained the same substances.

The trial team have also updated the information sheet to point out a small risk of irregular heart rate called atrial fibrillation that has recently been associated with EPA treatment and also a small increase in bleeding risk seen in a clinical trial of Vazkepa for those patients who already take anti-coagulant medication like warfarin. Neither of these new findings has altered how the trial is conducted.

People who are already in the trial and have been taking the capsules already without any allergy problem will need to read an updated information sheet and will be contacted via telephone by their local research team in order to provide written informed consent again. The local research team will be able to answer any questions that you may have about this news item or other aspects of the EMT2 trial.

EMT2 trial update during the COVID-19 pandemic – Update December 2020

Thanks to the commitment of trial participants and research staff, the EMT2 trial remains open and is recruiting well. Some hospitals have needed to stop recruitment temporarily in the past few weeks due to pressure of COVID-19 work but follow-up of patients in the trial has continued unaffected. There is no suggestion that the active treatment in EMT2 (EPA) affects the body’s immune response to vaccines so we do not expect that participation in the EMT2 trial will affect any individual’s vaccination priority or response to it.

EMT2 trial in the COVID-19 recovery phase

Thanks to hard work by the research sites and the Clinical Trials Unit, trial participant follow-up and capsule delivery via courier continued largely unaffected during COVID-19 lockdown. Now comes the hard task of re-opening for recruitment as hospital services start to return to normal and research staff return to pre-COVID roles. We are working with research sites under NIHR ‘Framework for restart’ guidance to make this happen as fast as we can.

COVID-19 UPDATE – MESSAGE FOR PARTICIPANTS

The Coronavirus epidemic (COVID-19) is causing disruption to all research trials taking place in the NHS, including EMT2. Research staff may have been asked to prioritise COVID-19 research and/or help treat patients with COVID-19. If this impacts on the trial from your perspective, your hospital research team will have been in touch to explain how to proceed. Otherwise, the trial is running as usual and your follow-up is unaffected. Below are two frequently-asked questions and answers from the participant letter, which was written at the start of the COVID-19 crisis, and which is available in full in the Downloads section:

DOES THE EPA IN THE ACTIVE CAPSULES AFFECT COVID-19 RISK?

We don’t think so. The EPA you are taking in the EMT2 trial is a natural omega-3 fatty acid substance, but we are using it at a much higher dose than you would get in your normal diet. There is no suggestion that omega-3 supplement use increases the risk of getting a viral infection or the course of an infection. There was a large international trial of the same dose and type of EPA that is being used in EMT2 called REDUCE-IT. The REDUCE-IT trial showed that there was no difference in the small number of patients who got influenza or other upper respiratory infections between patients receiving EPA or the dummy placebo.

WHAT HAPPENS IF THE NHS IS AFFECTED BY THE COVID-19 EPIDEMIC AND RESEARCH STAFF ARE NOT AVAILABLE TO MONITOR ME?

There are 10 NHS hospital sites with patients in EMT2 across England. Each hospital has a plan for how it is coping with COVID-19 and one aspect is to understand the effect on research trials if nurses and doctors become ill or have to go and help care for patients elsewhere in the hospital. Each hospital will make a decision whether it can safely monitor and support patients in all its trials including EMT2. Hospitals will probably stop new patient recruitment to trials so that they can look after patients already in trials. The excellent safety record of EPA and the fact that trial visits are infrequent and can be done by phone mean that EMT2 is less likely to be affected than other studies. If there is any problem running the trial, you will be contacted by your local hospital.

Please contact your research team at the hospital where you were recruited to the trial if you have any other questions.

OVERVIEW

This clinical trial has been designed to test whether a naturally-occurring omega-3 fatty acid called eicosapentaenoic acid (EPA for short) improves outcomes in patients who have an operation for the removal of bowel (also known as colorectal) cancer that has spread to the liver.

A small trial in Leeds suggested that a high-purity, high-dose preparation of EPA might be beneficial but only a bigger trial can give us a definite answer as to whether taking EPA will work. The EPA capsules are being compared with dummy (placebo) capsules so that we can be sure that EPA is or isn’t better than no supplement at all.

Taking part involves starting trial capsules before the operation and then continuing them after surgery even if the bowel cancer comes back. There are trial visits every 6 months that can either be combined with outpatient clinic visits or by telephone, if the hospital is a long way away.

Trial tests include the check-up CT scans that would be performed by the hospital department anyway, but also questionnaires about quality of life and some patients will be asked for extra blood tests.

NEWS

EMT2 Re-Started

Sept 2020 – The trial has re-started really well since July with 20 patients recruited by seven sites. We are seeking ethical approval to allow telephone consent in case hospital visits before liver surgery are restricted in the coming months.

Patients Recruited

253
As of Fri 08/10/2021

Target

448

STUDY TIMELINE

EMT2 is open for recruitment. The first patient was recruited in May 2018 and the patients are expected to be invited to join until the end of 2021. The last patients to join will take the capsules for at least 2 years so the results will be due in 2024.

PARTNERS

Trial Funder

Trial Organiser
Clinical Trial Research Unit
Trial Review and Approvals
The trial has been approved by a Research Ethics Committee, Health Research Authority and the Medicines & Healthcare Regulatory Authority who oversee all drug trials in the UK

FREQUENTLY ASKED QUESTIONS

WILL MY CANCER TREATMENT BE ALTERED BY JOINING THE TRIAL?

Your standard of treatment and care will not be affected by either volunteering or not taking part in the trial. Always remember that you can withdraw from the trial at any point, without giving a reason.

WHAT IS EPA?

EPA is one of the main omega-3 fatty acids found naturally in oily fish like sardines and mackerel, along with another fatty acid called DHA. DHA is thought to be important for brain and nerve development and function, whereas EPA has anti-inflammatory effects. The best evidence that omega-3s have anti-cancer activity is for EPA, which is why we are testing EPA on its own in EMT2.

WHAT ARE THE CAPSULES BEING USED IN EMT2?

The EPA capsules in EMT2 are pure EPA and give a high dose of EPA. The same capsules and dose of EPA has recently been shown to reduce risk of heart attack and stroke in individuals at high risk of such events in an international trial. The capsules (EPA and placebo capsules) are provided by Amarin Corp. and are called Vascepa®, which is already licensed for use in people with high blood lipid levels in the USA. The EPA is derived from fish and the capsule contains gelatin from an animal source so the trial is not suitable for Vegetarians.

WHY NOT TAKE AN OMEGA-3 CAPSULE AVAILABLE FROM THE SHOPS OR ONLINE?

Omega-3 capsules available on the high street contain a much lower dose of EPA than the trial capsules (approximately three times less EPA than a Vascepa® capsule). The fatty acid content in high street capsules is a complex mix of the multiple fatty acids found in fish oil, including some omega-6 fatty acids, the effects on cancer of which are unknown. We stipulate that no other omega-3 fatty acid supplements should be taken during the trial.

DOES EPA CAUSE ANY SIDE-EFFECTS?

Some people may experience some mild side effects relating to their digestive system such as nausea and diarrhoea, but these often can be minimised if the capsules are taken with meals.

HOW MANY TRIAL VISITS ARE THERE?

There will be regular contact by either telephone or study appointments (maybe 5-10), which will link to your standard care appointments, wherever possible. If transport is a problem then telephone follow-up can be done and capsules posted by Courier.
These visits will include a review of your progress, a health questionnaire, a prescription for new capsules and, for some participants, a blood test.

IS ALL MY TRIAL INFORMATION CONFIDENTIAL?

Confidentiality during the trial is important, and the information collected about you will be handled in accordance with the consent form and the 1998 Data Protection Act.

RECRUITMENT

RECRUITING CENTRES

The following hospitals sites are participating in the trial:
Basingstoke & North Hampshire HospitalBasingstoke
Queen Elizabeth HospitalBirmingham
St James’s HospitalLeeds
Queens Medical CentreNottingham
Northern General HospitalSheffield
Southampton General HospitalSouthampton
University Hospital AintreeLiverpool
Freeman HospitalNewcastle
Royal Free HospitalLondon
Addenbrookes HospitalCambridge
King's College HospitalLondon
University Hospital of Wales HospitalCardiff

TRIAL TEAM

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