Frequently Asked Questions
Information for participants
Click on the topics below for more information:
- Why are you doing THRIVE?
- Why have I been asked to participate in THRIVE?
- What does taking part involve?
- Are there any additional blood tests or procedures involved in participating?
- What are the potential benefits of taking part?
- What are the possible risks or side-effects of taking part?
- What do I have to do to join the study?
- What if I do not want to enter the study?
- What if I want to withdraw from the study?
- Will participating affect my other medical treatment?
- What happens if I need to go into hospital?
- Will my participation be kept confidential?
- Is it OK to go on holiday?
- How long will I be involved in THRIVE?
- When will I know the results of THRIVE?
Why are you doing THRIVE?
People who have already had a circulatory problem such as a heart attack or stroke are at increased risk of developing further circulatory problems. One of the causes of this circulatory disease is having too much LDL (bad) cholesterol in the blood. We know that lowering this bad cholesterol in the blood with drugs such as statins reduces the risk of a heart attack or stroke. Everybody in this study will therefore be given tablets to lower their bad LDL cholesterol. However, despite effective LDL-lowering treatments, some people still suffer recurrent heart or circulatory problems. This study hopes to find a way of reducing these risks even further.
As well as LDL (bad) cholesterol there is also HDL (good) cholesterol in the blood. In general, people with higher levels of good HDL cholesterol have fewer heart attacks, strokes or circulatory problems than people with lower levels. Niacin is a medication that increases the amount of good cholesterol in the blood. However, although niacin has been in use for more than 50 years, it is still not clear whether it prevents heart attacks and strokes. Part of the difficulty has been that patients treated with niacin frequently develop flushing (reddening) of the skin, and sometimes other side-effects, making it difficult for people to take their tablets regularly. Extended release (ER) preparations of niacin reduce these side-effects but do not completely avoid them. A new treatment, laropiprant, has been developed which reduces the flushing caused by niacin. It works by blocking the dilatation of the blood vessels in the skin responsible for the flushing. Therefore laropiprant has been combined in a single tablet with extended release (ER) niacin to make it easier for people to take these treatments regularly. This combination is known as ER niacin/laropiprant.
The aim of THRIVE (Treatment of HDL to Reduce the Incidence of Vascular Events) is to find out whether long-term treatment with ER niacin/laropiprant in people who have survived a heart attack, stroke or some other circulatory problem produces benefits by raising HDL (good) cholesterol. It is hoped that this will prevent heart attacks, strokes or the need for arterial bypass procedures (known as revascularisation) but this is as yet unknown.
Why have I been asked to participate in THRIVE?
THRIVE will involve about 25,000 men and women from the United Kingdom, Scandinavia (Denmark, Finland, Norway and Sweden) and China who, like you, are being invited to take part because they have a history of vascular disease. An invitation will have been sent to you from a Specialist from your local hospital because they think you might be suitable for the study. It is up to you to decide whether or not you would like to take part in this study.
What does taking part involve?
Everyone taking part will have agreed to do so voluntarily, knowing that it may involve them in taking study treatments for at least 4 years. If you agree to take part, the study nurse will need to see you in the clinic 3 or 4 times in the first 6 months and then 6-monthly. You will be asked some questions about your medical history, have a blood sample taken and measures of your height, weight and blood pressure. If you are eligible and wish to enter the study, you will be asked to sign a Consent Form and be given a copy to keep.
If you are not on a statin for your cholesterol you will be given study simvastatin 40 mg daily to take regularly. Alternatively, if you already take a cholesterol-lowering statin tablet, you will be asked to stop this and take study simvastatin 40 mg daily instead (with or without ezetimibe depending on the dose of statin you have been taking previously). If you are initially given simvastatin 40 mg alone and this is found not to lower your cholesterol enough, it will be changed to the combination of simvastatin and ezetimibe at the second visit.
For your early visits it will be helpful if you could fast. This means avoiding any food or drink (other than water) for at least 4 hours before the clinic. This helps with the reliability of the blood tests and these visits would be scheduled at a time of day to make it easy for you. At these visits the nurse will measure your cholesterol and give you these results.
Early in the study, you will be given a treatment-pack containing active ER niacin/laropiprant tablets. You will be asked to take one tablet a day for the first 4 weeks increasing to two tablets a day for the following four weeks. The study tablets are to be taken with food in the evening or at bedtime. After 8 weeks of taking laropiprant tablets plus the LDL-lowering tablet you would visit the clinic again. You would then decide if you are willing to continue taking study tablets for at least 4 years. The purpose of this part of the study is to make sure that the ER niacin/laropiprant agrees with you. If you do get side-effects at this stage, it may not be appropriate for you to continue in the study.
If you decide to continue, you will be given a further supply of study tablets and an appointment for 3 months time. Throughout the rest of the study, there will be three tablets to be taken each day, the LDL-lowering tablet (simvastatin or ezetimibe/simvastatin) and two tablets which contain either active ER niacin/laropiprant or a similar looking inactive dummy substance called a 'placebo'. Whether or not a participant receives active or dummy tablets (placebo) will be determined randomly (like tossing a coin). Each participant will have a 50% chance of receiving active ER niacin/laropiprant combination tablets and a 50% chance of receiving placebo ('dummy') tablets. The type of study treatment being taken will not generally be known by you or your doctor. This information will be known only by certain staff at the coordinating centre in Oxford, but it would be made available to your doctor if this were ever medically necessary. This design helps ensure that reliable information will be obtained about the effects of these potentially important treatments.
After the first 6 months you would need to attend for an appointment every 6 months. It will not be necessary to fast for these clinic visits. At every visit (each lasting 20-30 minutes), the study nurse will ask how your health has been since the last appointment, take a blood sample and provide you with more study treatment as required. In the unlikely event of a problem, we may need to ask you to return for an extra visit.
Throughout the study, your own doctors would remain fully responsible for all your other medical care as usual. However, if you did experience any unexpected symptoms which you thought may be related to either of the study treatments, medical advice is available at all times through a 24-hour Freefone service.
Are there any additional blood tests or procedures involved in participating?
You would need to have a blood test done every time you came to the study clinic. These would be done for a number of reasons. Firstly they would check that it is safe for you to continue taking study treatment. We would also use blood tests to decide which treatment you are given for your 'bad' LDL-cholesterol and samples would be sent to a central laboratory in Oxford for more detailed analyses (and your GP would be informed of the results of these). At some visits you may be asked to provide a urine specimen and measurements of your height, weight and blood pressure would also be recorded.
What are the potential benefits of taking part?
We hope that the study treatment may help you. However, this cannot be guaranteed. The information we get from this study may help us to treat future patients with vascular disease better and may help to prevent many thousands of heart attacks and strokes.
What are the possible risks or side-effects of taking part?
Laropiprant is not known to have any particular side-effects, but it is possible there may be some, as yet unknown, side-effects.
Niacin is a drug that has been used to treat cholesterol for over 50 years. However, its use has been limited by skin flushing (defined as a feeling of warmth, redness, itching and/or tingling) as well as other side effects it can produce. Even though laropiprant should reduce any flushing due to the niacin, some people (20-30% in the first week) taking ER niacin/laropiprant may still experience flushing episodes. These episodes are more likely to occur within the first few days of starting treatment and then usually disappear by the end of the first week. They may then recur if you miss the tablets for a few days and then restart. Although occasionally unpleasant, these flushing episodes are not dangerous.
Some people may also experience other side-effects due to niacin, including: gastrointestinal symptoms (tummy upset, nausea or diarrhoea); headaches; skin rashes and rarely allergic reactions. Occasionally niacin can also cause liver problems (fewer than 1 in 100 patients) and this will be monitored by a regular blood test every time you come to the clinic. These liver problems usually resolve when treatment with niacin is stopped but rarely can make people unwell. Niacin can also increase blood sugar levels particularly in people with diabetes. The significance of such changes is unclear, but will be monitored during the study.
The simvastatin and ezetimibe are generally well tolerated although occasional side-effects have been reported. Very occasionally they can cause a muscle problem called 'myopathy' which causes muscle pain and/or weakness with abnormal blood tests, but this is rare (typically less than 1 in 10,000 affected per year among people of European origin but, information from the study so far shows rates of about 1 or 2 per 1000 per year in Chinese people). The risk may be increased slightly by taking additional niacin. If, after joining the study, you were to develop some unexpected symptoms, in particular soreness or weakness of your muscles which is not the result of exercise or some other activity, you should contact your study nurse, or one of the doctors at the coordinating centre (24 hour Freefone 0800 585323) in order to obtain advice.
What do I have to do to join the study?
If you have been invited to participate in THRIVE, you would have been sent an invitation letter (we will have previously informed your GP and sought agreement to invite you to participate). If you feel you would like to participate in this study you should call the coordinating centre on Freefone 0800 585323 to confirm your first appointment. You may be asked a few questions to confirm that the study is suitable for you and to collect some further contact information in case we need to contact you before your first visit.
What if I do not want to enter the study?
If you do not want to participate in THRIVE, then please indicate this on the form that has been sent to you and post it back to us in the Freepost envelope provided, or call the coordinating centre on Freefone 0800 585323. This will ensure that you do not get approached again. If you decide not to take part, your usual standard of medical care will not be affected.
What if I want to withdraw from the study?
If you do decide to take part, you would, of course, be free to withdraw from the study treatment at any time without necessarily giving any reason (and without adversely affecting the medical care you can expect from your own doctors). If you stop during the first few months then no further enquiries would be made of you. But, if you decided to stop after the first few months, we would like to remain in contact with you for the next several years - even if you are no longer taking the study treatment.
Will participating affect my other medical treatment?
There are a few medications that should not be taken with simvastatin: for information on some of the medications that should be avoided if you are participating in THRIVE, please click here. If you are taking any of these prior to your first visit we would recommend that you do not participate. If they are started after you have entered the study, please call your nurse or the coordinating centre on Freefone 0800 585323 to discuss this further. All other prescribed treatments can be taken as usual. There are no other lifestyle or dietary restrictions required.
What happens if I need to go into hospital?
If you decide to participate in the long-term part of the study we will give you a THRIVE participant card. Please take this with you and show it to the doctors looking after you. They can contact a study doctor on Freefone 0800 585323 to discuss the study if this is necessary. Please remember to tell your study nurse about the admission at your next study visit.
Will my participation be kept confidential?
The coordinating centre would seek information from participants' own doctors and from NHS and other central registries about any serious illnesses (such as heart attacks, strokes, cancers etc) that occur. All such information would be used, in confidence, only for medical research purposes and for routine regulatory and audit purposes. When the research study finishes, we will inform you and your GP of the study results. We will also publish the study results in a professional medical journal as soon as possible after the study finishes. You would not be identified individually in any published report.
Is it OK to go on holiday?
Of course! We can organise your clinic visits to fit your itinerary. It would be important to take your study treatment with you and if necessary we can provide a letter for your travel insurance company/customs about this.
How long will I be involved in THRIVE?
Participation in THRIVE does require a commitment to take the study treatments regularly for at least 4 years and to attend study visits regularly. If you do not think that you would be willing or able to do this, then it would be better not to join in the first place.
When will I know the results of THRIVE?
We will write to you and your GP as soon as the results of the study are available (which is likely to be a few months after your final visit). We will also publish the study results in a professional medical journal as soon as possible after the study finishes.
