CAMPATH, Calcineurin inhibitor reduction and Chronic allograft nephropathy trial

PATIENT INFORMATION SHEET

Information about a study you might be asked to join

What is the purpose of the study?

The study is called 3C. It aims to test new ways to improve kidney transplants and make them more effective.

Kidney transplantation is a very good treatment for people whose kidneys no longer function sufficiently to keep them alive. Unfortunately, kidney transplant function inevitably declines over time. On average, after about 10 years the transplant “fails” and the recipient either receives another transplant or returns to dialysis.

The aim of 3C is to test two ways to prevent this failure – and help transplant patients now and in the future live longer with better quality of lives.

All people who receive a kidney transplant need drugs to prevent their body from “rejecting” the new kidney. Standard medications to prevent rejection may also cause long-term damage to the kidney. The 3C Study is testing two new treatments which might avoid this long-term damage. No one knows which of the two treatments, if any, are better than existing medication.

The treatments being tested relate to your immediate treatment after transplant, and your long term care, starting about six months after your transplant. You may hear the immediate treatment referred to ‘induction treatment’ and the longer term care as ‘maintenance treatment’.

Why have I been chosen?

You have been introduced to the study because you may be about to receive a kidney transplant.

Do I have to take part?

No. It is up to you to decide whether or not you take part. You may wish to discuss your decision with your close family or friends and with your consultant. If you do decide to take part, you will be asked to sign a consent form. You will still be free to withdraw at any time and without the need to give a reason. If you decide not to take part, or later decide to withdraw, it will not affect the care you receive in any other way. This includes decisions about whether or when you would be suitable for a transplant.

What will happen to me if I take part?

We do not know which method of treatments, or combinations of treatment, is best. Patients will be put into different treatment groups, selected by chance (randomly), like the toss of a coin. At the end of the study scientists will analyse which treatment produces the best result. It may be that there is no clear cut answer.

At the time of transplant (‘induction’ treatment)

If you take part in the trial you will be allocated a treatment group at the time of your transplant operation. A computer will decide by chance (like the flicking of a coin) which induction treatment you receive. This will either be:

1. Standard treatment: basiliximab followed by standard medications. These will include steroids for at least 3 months, after which time they may be stopped if your doctor wishes to do so.
2. New treatment: CAMPATH treatment followed by lower doses of standard medications. Patients treated with CAMPATH will not need steroids.

Six months later (‘maintenance’ treatment)

Once again, your long-term treatment will be chosen at random by a computer. This will either be:

1. Standard maintenance treatment; or
2. New treatment: you would switch to the new drug being tested. This new drug is called sirolimus (Rapamune).

What then?

We plan to follow your progress for many years. During the first year, assessments related to this study will take place at the same time as your regular hospital visits and should not require any extra visits. These study assessments should not add significantly to the time taken for your regular care. After you have been in the study for one year, we will start to send you annual questionnaires (for about four years) to monitor your progress. Throughout this time and following it we would like to find out what happens to you by collecting information from national registries which routinely hold information about events that are important to the study.

Expenses and payments

You will not be paid for taking part in this study. There should be no extra cost to you as all the assessments needed for the trial will be done alongside your routine care. In the unlikely event that any extra visits are required it will be possible to reimburse reasonable travel expenses.

What do I have to do?

Involvement in this study should not require any extra visits or inconvenience to you. Like all transplant recipients you will need to take medication regularly and have regular blood tests.

What are the drugs that are being tested?

Induction treatments: these are given around the time of surgery, to reduce the risk of the body rejecting the new kidney in the first few weeks and months, when the risk of rejection is greatest. The new kidney is attacked by the patient’s immune system because it is ‘foreign’. The 3C study will compare two such induction treatments, which seek to prevent such an attack:

• CAMPATH has been in clinical use for many years, but its use for treating kidney patients long-term is not known. CAMPATH prevents some cells of the immune system from attacking the new kidney. The treatment is specific to those cells of the immune system that attack the kidney. The treatment does not affect other cells. CAMPATH has been used in organ transplantation and is licensed to treat some types of leukaemia. It is also used in conditions where the immune system is over-active. It is given by injection at the time of surgery, and a second dose may be given 24 hours later.
• Basiliximab is the current standard induction treatment. It also targets immune cells that can damage the new kidney, but works in a different way.

Maintenance treatments: these are drugs taken on a daily basis after transplantation also in order to reduce the long-term risk of rejection. The 3C study will compare two such treatments:

• Sirolimus has also been used for many years and is a drug which is licensed for use in transplant patients. It is taken by mouth once a day, and the amount given will be tailored to each individual’s requirement. The level of sirolimus can be measured by a blood test which guides how much each patient is given.
• Tacrolimus is part of the current standard maintenance treatment, and like sirolimus the amount given is tailored to each individual’s requirement based on blood tests.

What are the alternatives for treatment?

If you choose not to take part in this study, you will receive the treatment which is standard at the hospital where you have your transplant. This may include some of the drugs being tested in the 3C study.

What are the side-effects of the study treatments?

Apart from CAMPATH, all the drugs used in the 3C study are commonly used in kidney transplantation. As with all transplant drugs, they have side-effects. All transplant drugs come with the risk of infections and very rarely cancer. If you develop any side-effects from your treatment you will be able to discuss this with the doctors looking after you.

CAMPATH has been in use for many years. It does not seem to increase the risk of serious infections after transplantation. However, this will be closely monitored during the 3C study. Some patients develop short-term ‘flu-like’ symptoms at the time of the first dose. This lasts for no more than a few hours and is easily controlled with other medications. Basiliximab is usually well-tolerated, although rarely causes an allergic-type reaction.

The most common side-effects of sirolimus include mouth ulcers, rashes, oedema (swollen ankles) and diarrhoea. Its use is also associated with mild anaemia, slight elevations of fat levels in the blood and protein in the urine. Tacrolimus can cause diarrhoea, insomnia, headache and a tremor. It can cause deterioration in kidney function, and elevations in blood sugar and occasionally potassium (a salt in the blood).

What are the other possible disadvantages of taking part?

If you have private medical insurance we would recommend that you check with your insurance company before agreeing to take part, to ensure that doing so will not affect your insurance.

For women: Mycophenolate - which all patients receive in the trial - is not safe in pregnancy. The safety of CAMPATH in pregnancy is not known. If you become pregnant during the trial (or wish to do so), you should tell your doctor so appropriate action can be discussed.

For men: Please share this information with your partner if it is appropriate. If you are allocated to receive CAMPATH and your partner might become pregnant, you must use reliable forms of contraception during the first six months of the trial. If you are allocated to receive CAMPATH and your partner becomes pregnant during the first six months of the study, you should inform your study doctor so appropriate action can be discussed.

What are the possible benefits of taking part?

We cannot promise the study will help you, but we hope that some patients in the study will experience benefit. We expect all kidney transplant patients to benefit from the findings in due course.

What happens at the end of the study?

You and your transplant doctors will be informed of the study results when all patients have been in the trial for 2½ years. Based on these, you and your doctors can decide whether or not you should continue on the treatment you have been given as part of the study. The results will be made public in professional medical journals and at international conferences as soon as possible after the study finishes. At no time will you be identified personally in any published report.

What if there is a problem?

If you have any complaint about the way you have been dealt with during the study or concerns about any possible ill-effects of treatment, please call the study team on Freefone 0800 585323. More detailed information on this is given in Part 2. The contact number for complaints is Freefone 0800 585323.

Will my taking part in this study be kept confidential?

Yes. All information about your participation in this study will be kept confidential. Details about this are included in Part 2.

Contact details

Any questions about the study should be directed to the study Principal Investigator at your hospital or the study’s coordinating centre in Oxford.

The study coordinating centre can be contacted:

• By telephone: 24 hour Freefone service 0800 585323
• By post: 3C Study, CTSU, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LF
• By e-mail: ccc@ctsu.ox.ac.uk