Participating Hospitals FAQs
If a patient is on a beta-blocker (selective or non-selective) such as Bisoprolol, Metoprolol, Atenolol, Propranolol (Inderal, InnoPran), Nadolol (Corgard), Pindolol (Visken), etc. they are ineligible for BOPPP.
However, if a patient is on a beta-blocker for managing hypertension that can be replaced with Diuretics e.g. Indapamide; ACE inhibitors e.g. Ramipril; or, Angiotensin II receptor blockers e.g. Losartan, etc. then the beta-blocker should be discontinued for 1 week. After a 7-day washout period, they are eligible for BOPPP providing they meet all other eligibility criteria.
If this six month period has passed, this participant should be re-evaluated at their next annual varices surveillance appointment, unless they receive an endoscopy as an inpatient. Please maintain accurate pre-screening records to keep track of patients like these.
Photo-documentation of oesophogeal varices are recommended in the trial protocol but we accept that there will be times where your image capture software fails for whatever reason. Photos may also not have been taken in OGDs prior to your site being opened for recruitment.
As a minimum, please document on ALL OGD reports:
- Size of OV
- Number of columns of OV
- Presence/absence of red signs – this is important as red signs suggest increased risk of bleeding and exclude the patient.
- Any gastric or duodenal varices present
In this case, very helpful to make a file note around eligibility review to say that patient has been diagnosed endoscopically with small OV although photo-documentation is suboptimal on report. That way, we know there has been PI oversight and discretion, and eligible patients are not barred from appropriate recruitment because of this issue around the photos.
Yes – as the patient has an active malignancy without curative therapy planned. Whilst TACE will delay malignancy development it is not curative therapy.
As long as the patient has a diagnosis of cirrhosis and portal hypertension and small oesophageal varices, then the presence of a portal vein thrombus will not exclude the patient.
If the patient has a thrombus without cirrhosis, then the patient would not be eligible as they do not meet inclusion criteria.
Please liaise with your PI and / or sub-investigators regarding concerns over inclusion / exclusion criteria and email email@example.com if your are not sure.
Any patients on medication for hypertension that do not involve a beta-blocker should be eligible for BOPPP. There are no known drug interactions with the active IMP (Carvedilol) and Lorstan so this patient would be eligible.
If you have any concerns regarding drug interactions – always refer to the Carvedilol Summary of Product Characteristics found in the Site Resources web-page (click Summary of Product Characteristics) and speak with your PI or sub-investigators. Alternative you can always email firstname.lastname@example.org.
At site level, the PI / sub-investigator should do as per standard of care for each patient. If there are clinical concerns regarding a cardiac arrhythmia it might be prudent to determine the presence of 2nd/3rd degree heart block by obtaining an ECG – otherwise the absence of 2nd/3rd degree heart block in the patients medical history is sufficient to confirm that the patient does not have this exclusion criteria.
We should not exclude patients if they are non-English speaking and we will look into translating the PIS and ICF on a case by case basis. In all cases, please contact email@example.com as soon as you find an eligible non-English speaking patient.
When you contact us, please confirm the language required and the support that will be needed for the patient to participate in BOPPP. Consider the use of “language line” that would be used during standard care appointments and if a translator is required in person.
If translators are needed in person you must guarantee that the patients appointment will run on time or in a research focused clinic as this will affect translator availability and time required to complete the visit.
Research nurses can be involved in the consent process but as BOPPP is a CTIMP, the Principal Investigator or a delegated sub-investigator need to confirm eligibility and complete the consent process by signing the consent form.
Your site will be reimbursed up to £30 per patient per visit for three research only visits. These are at Screening, Baseline and the Week 1 up-titration visit. If Screening and Baseline occur during a standard of care appointment, then travel expenses would not be appropriate to pay.
Please contact firstname.lastname@example.org if the patients travel expenses would be in excess of the £30 per patient per visit so we can discuss this with you on a case by case basis.
Procedures and Resources
BOPPP medication levels will be monitored by the BOPPP Pharmacist (Angela Cape) in an ongoing manner. The BOPPP Pharmacist is unblinded so they will know if stocks are getting low and may affect trial delivery. Monitoring will include monthly assessment of site screening, recruitment and withdrawal. If you have concerns over stock levels, please email the trial Pharmacist (email@example.com) and BOPPP email account (firstname.lastname@example.org).
Firstly, ascertain what the participant wants to withdraw from as this may refer to not completing the participant questionnaires, not taking the BOPPP medication and/or withdrawing permission from allowing us to analyse the participants Health Episode Statistics (HES) data.
Secondly, contact email@example.com to inform the central trial team so this can be documented and discussed with the BOPPP Statistician. In the case of withdrawing from BOPPP medication, please ask the participant if we can still collect data about their health and ascertain why the participant would like to withdraw. Record the discussion in patients medical notes and email
firstname.lastname@example.org, completing the relevant pages on MACRO.
Drug & Side Effects
In all situations, where you are concerned with side effects from the medication you are taking for BOPPP, please contact your BOPPP research nurse at the Hospital that is treating your liver disease. The contact number is in the Participant Information Sheet that was given to you when you were approached to participate.
Below are some symptoms and advice that may be associated to the BOPPP medication:
Chest pain – If you have any chest pain that is ongoing at rest – please go to your local Emergency Department. If you are experiencing chest pain that is intermittent – please go to your GP.
Fainting or collapse – If you have fainted or collapsed more than once – please go to your local Emergency Department. If you have fainted or collapsed once – please go to your GP.
Abnormal heart beats – If you have noticed that your heart is beating abnormally slow or fast – please go to your GP.
Rash – If you have noticed any rash on your skin that is new – please go to your GP.
Erectile dysfunction – If you have had any issues or problems with erections during intercourse – please go to your GP.
If you have lost your BOPPP medication, please immediately call your research nurse. Their phone number will be in the Participant Information Sheet that was given to you at the start of the trial.
Once you have spoken to the research nurse, you may have to visit the hospital again to collect your medication. If you are not able to visit the hospital, your BOPPP medication may be posted to you.
If you temporarily forget to take the BOPPP medication, pick up where you left off by taking your medication as scheduled. Never try to make up for missing doses.
At each visit to hospital, the research nurse will ask you how often you took your BOPPP medication. Please make sure you let the research nurse know at that time.
BOPPP is designed for patients with liver cirrhosis and small oesophageal varices. If you have liver cirrhosis and small oesophageal varices there is a Participant Information sheet that can be viewed here.
After reading this information sheet, if you are still interested in taking part, you will need to speak with the clinician dealing with your liver disease at the Hospital you are being treated at. To find out if the Hospital in charge of your liver disease is recruiting patients for BOPPP, please click here.
Sometimes we do not know which treatment is best. To find out, we compare different treatments by putting patients into groups with each receiving a different treatment. This would apply to anybody taking part in BOPPP. However, by taking part, you will be closely monitored for the duration of the trial and will be in regular contact with a Liver Unit Research Nurse.
At the end of the study, we will provide every patient a non-technical summary of the trial results. This document will show if early treatment with beta-blockers reduces the risk of bleeding in patients with liver cirrhosis and small oesophageal varices. This will allow you, your Liver Consultant and General Practitioner make an informed decision about your best long term treatment option.
It is very important that your GP knows about your participation in BOPPP. This is because there may be developments in your health where your GP needs to know what medications you are taking to avoid unnecessary drug interactions that might make you feel worse.
After you are given your BOPPP medication, the Research Nurse at the Hospital treating your liver disease will write to your GP, telling them that you are in the BOPPP trial. The GP will be provided with a copy of the Participant Information Sheet that you read before you decided to take part.
Your GP may be contacted by the Hospital treating your liver disease if you experience any adverse event out side of hospital to obtain relevant information to make sure that the severity of the event and relationship to the BOPPP medication is assessed accordingly.
Sometimes we do not know which treatment is best to give patients. To find out, we compare different treatments by putting patients into groups with each group receiving a different treatment. To ensure the groups are the same to start with, each patient is put into a group by chance i.e. randomly, selected using a computer that has no personal information about you.
One group is called the ‘active’ group and will receive Carvedilol and the other group, called the ‘control’ group, will receive a placebo treatment. There is a one in two chance of being allocated to either treatment (like flipping a coin).
The placebo treatment is a blank (or dummy) treatment and is made to resemble a Carvedilol tablet. Placebo does not contain any active drug. Using a placebo is called a ‘placebo controlled trial’ and ensures that the trial results are reliable by checking that any effects are actually due to the active drug and not influenced by you or your doctor from what we ‘expect’ to happen.
Neither you nor the research team nor the medical team will know which treatment you are receiving so this does not influence the trial results. This is called ‘blinding’. However, should we need to know what treatment you are on, there are mechanisms in place to ‘unblind’ if necessary.
All participants will be followed up at regular 6 month intervals and will have various routine tests. All of the tests in BOPPP are standard as part of your normal medical care when you have liver disease (cirrhosis).
There are two research specific questionnaires that we ask participants to complete: 1) a Quality of Life questionnaire and 2) a Healthcare Use questionnaire.
Trial treatment will be started at a small dose and increased after one week if required. You will be supported by a research nurse through your participation in the trial. This will not include conventional clinical care.
We ask all participants to take the study medication (beta-blocker of placebo) for 3 years in total. This does not stop you from withdrawing at any time and for any reason – without affecting your clinical care at your Hospital.
You will be asked to take one or two tablets every day. Neither you nor the research team nor the medical team will know which treatment you are receiving so this does not influence the trial results. This is called ‘blinding’. However, should we need to know what treatment you are on, there are mechanisms in place to ‘unblind’ if necessary.
Every 6 months, you will be seen at your hospital by your usual Consultant team as part of routine clinical care and have the usual range of tests that you would have normally. There are no extra research tests in this trial. During the same visit, you will also be seen by a Research Nurse who will ask you to complete 2 research questionnaires. Your study medication will be given to you at this visit.
Some travel insurance companies will ask you if for you are taking part in a clinical trial. This may affect your travel insurance insurance premiums with some companies, so you will need to do some research for companies will allow you to take part without affecting your premiums.
If you know of any travel insurance companies that are not influenced by patients taking part in clinical trials please email email@example.com so we can include that information on this website.
If you are aware that your BOPPP patient has had an untoward medical event, please do the following:
- Contact the patients Hepatology consultant and or/ BOPPP research team at the Hospital they are being treated for their liver disease using the contact information in the Participant Information Sheet that you were sent when your patient consented to take part.
- Alternatively, if the above contact details are not obtainable – email firstname.lastname@example.org to inform the central trial management team that an adverse event has been identified, so they can inform the BOPPP research team involved on your behalf.
- Remind your patient to contact the BOPPP research nurse.
Note – in the event that an adverse event needs to be followed up through to a conclusion, the Hospital treating your patients liver disease may need medical information from you to ensure that the severity of the event and relationship to the trial medication is assessed accordingly.