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What is the purpose of the TRACK trial?

People with advanced kidney disease have high rates of heart and vascular disease. There are few treatments that are proven to improve the health of these patients. The purpose of this research study is to find out whether a low dose of blood thinning medication (rivaroxaban 2.5 mg twice daily) can reduce heart and vascular disease (such as heart attack and stroke), which are very common in people with advanced kidney disease. This dose of rivaroxaban is half the dose required to achieve the full blood-thinning effect at this level of kidney function.

People with advanced kidney disease not only have higher rates of heart and vascular disease compared to the general population, they also have higher rates of bleeding. As such, it is important to study the potential benefits (less heart and vascular disease) and the potential risks (more bleeding), to understand whether these medicines are beneficial overall.

With this research we hope to learn whether the blood thinning medicine, low-dose rivaroxaban, has more benefits than harms in preventing heart and vascular disease in people with advanced kidney disease.

Who can participate in the trial?

Adult people who have advanced stages of kidney disease (stage 4 or stage 5), or those who need long-term dialysis are eligible to participate. Additionally, they need to have pre-existing heart or vascular disease or at risk of having heart or vascular disease, such as age over 65 years or diabetes.

However, not all patients with kidney disease and heart or vascular disease can take part. Kidney doctors will assess whether potential participants meet all required criteria.

How many people will participate in the trial and how long the trial will last?

Approximately 2000 people will take part in this trial. The trial will last about 5 years, but many participants will be in the study for between 2 to 3 years, depending on when they join the trial in the 5-year period.

What treatment will be tested in the trial?

As part of this study, participants will receive either low-dose rivaroxaban tablets (the blood thinning medicine) or a placebo (a look alike tablet that contains no active medication). Participants will be randomly assigned (like a flip of a coin) to receive either the rivaroxaban or the placebo. This study is a ‘double blind trial’, so neither participants nor their treating doctor (or the other staff in the hospital) will know which tablet (rivaroxaban or placebo) is given. If participants ever have a problem such as needing an urgent operation, and their doctor needs to find out which tablet they were assigned, he/she can do so. 

Rivaroxaban is blood thinning medication. It is approved by medicine regulatory bodies in the USA, Europe, Canada and Australia, for the prevention of heart and vascular disease in people with normal kidney function or mild to moderate kidney disease, but it is not specifically approved in people with advanced kidney disease. This trial is designed to see if the medication is beneficial to patients with advanced kidney disease.

What does participation in this research involve?

Before starting in the study (Screening):

Local doctors and study nurses will review previous blood tests and medical records to see whether potential participants fit the eligibility criteria and whether they are willing to participate in the trial.

Start of the study (Run-In):

Participants that are eligible for the study and agree to participate by signing the Study Consent Form, will then enter the run-in phase of the study. During this phase, all participants will receive placebo tablets for approximately 3 weeks, to make sure they can follow the study medication schedule. Local doctors and study nurses will collect the following information:

Collection of your clinical data will begin from the time you sign the Study Consent Form. At the start of the study, this will include:

  • demographic information (e.g. birth date, gender, self-reported ethnicity)
  • details of your medical history and medications you are taking,
  • limited medical examination (blood pressure, heart rate, body weight)
  • answers from a short questionnaire about their well-being
  • laboratory results from recent routinely collected pathology tests (no new tests are required).

Randomisation:

If participants are able to take the study medication regularly, at the end of the run-in phase of the study, they will be eligible to be randomly (like the toss of a coin) assigned to either low-dose rivaroxaban or placebo. At this visit, the study team will:

  • check whether participants have taken the study medication regularly (by completing a count of the tablets taken)
  • check their willingness to be randomised
  • use a computer system to randomly assign participants to a study medication
  • provide a supply of the study medicine in bottles

Study visits (Follow-Up):

The study staff will contact participants by phone and at regular clinic visits, during the study. If participants are needed to be seen at any other time, they can contact the study staff or their kidney specialist.

Clinic follow-up visit: Clinic visits take place every 6 months following randomisation. At these clinic visits the study staff will:

  • Ask whether participants have taken the study medicine as prescribed
  • Ask whether participants have been admitted to the hospital since their last study visit
  • Ask about any heart, vascular or bleeding events since their last study visit
  • Ask participants to complete a short questionnaire about well-being
  • Dispense the next supply of study medicine to last until the next study visit

Telephone follow-up assessment: will take place at 1 month and 3 months following randomisation, and then every 6 months thereafter between clinic follow-up visits. At these phone call follow-ups, the study staff will ask about:

  • Ask whether participants have taken the study medicine as prescribed
  • Ask whether participants have been admitted to the hospital since their last study visit
  • Ask about any heart, vascular or bleeding events since their last study visit

Towards the end of the study, participants will undergo a final visit which is the same as a clinic follow up visit (see above). At this final visit, all study medication should be returned to the study team. This final clinic visit will occur after 5 years, or when the study is finished, whichever is sooner.

End of study:

The study team will contact participants via telephone 4 weeks after you’re the final study visit to find out about health status after the study medication has cleared from their system.

Are any tests required during the trial?

No extra blood tests or study visits are needed specifically for this trial. Tests required as a part usual medical care will be conducted by local doctors as required.

What happens if a participant stops taking the study medication during the trial?

It is okay to stop taking the study medication at any time for any reason. Even if a participant stops taking the study medication permanently, the study team will ask them to continue to follow-up so that they can monitor your health and the effects of the study drug. If a participant stops taking the study medication temporarily, the study team will ask them to record the ceasing and recommencing dates and reasons on a Patient Alert Card, that will be provided.

What are the possible benefits of taking part in the study?

This trial will improve medical knowledge and may help future patients with advanced kidney disease who are at risk of heart and vascular disease, but it is not likely that it will be of direct benefit to participants. The research will provide doctors with important information about the benefits and harms of blood thinning medications in people with advanced kidney disease.

What are the possible risks of taking part in the study?

All medical treatments involve some risk of harm. The known risks of this study are mainly around the extra bleeding risk from blood thinning agents, but there may be risks associated with this study that we don’t know about yet or new problems that might come up during the study.

Even without a blood thinning medication, the risk of major bleeding in people with advanced kidney disease is five times higher than in patients with normal kidney function, with about 1 in every 10 (10%) patients with advanced kidney disease having a major bleeding event per year. Blood thinning medications, such as the study medication, are likely to increase this bleeding risk to around 1 in every 8 (12%) patients.

These bleeding complications can involve various body organs that could be minor (e.g. bruising), or rarely major which can be life threatening.

  • Up to 1 in 10 people:
  • Stomach, bowel, nose or gum,
  • Skin or under the skin such as bruising,
  • Oozing from a surgical wound,
  • Up to 1 in 100 people:
  • The brain or inside the skull,
  • Joints- causing pain and swelling,
  • Up to 1 in 1,000 people:
  • Muscle- causing swelling and pain.

Because of the increased risk of bleeding, there is also a risk of developing a low blood count (anaemia). Common symptoms of anaemia include decreased energy levels and getting tired with minimal activity.

Participants will be monitored closely by their doctors to minimise this risk. Participants need to tell their doctors as soon as possible if they experience any of the following symptoms:

  • Pale skin, tiredness and breathlessness,
  • Bruising,
  • Headache,
  • Swelling and pain of a joint or muscle,
  • Bleeding from mouth or nose,
  • Dark black coloured stool,
  • Brown or black vomit,
  • Blood in vomit or stool,
  • Oozing of blood from a surgical wound if you have undergone an operation.

Other side effects from rivaroxaban have been seen in clinical studies but have been rare, seen in up to 1 in 10,000 (<0.1%) of patients taking the medication. Some of these side effects are severe and include severe skin reactions, fevers, inflammation of internal organs (including the liver) and allergic reactions.  Participants can discuss these potential side effects with their study doctor at any time, including during the study.

We will provide participants with a Patient Alert Card that they should carry with them at all times. The card will provide details of the local study team and the study medication.  Participants should always let any treating doctors and nurses know that they are taking a study medicine. If their doctor decides to prescribe any new medication, participants are admitted to hospital for any reason, or are likely to undergo any operation, their doctors should be made aware of participation in the trial by showing the Patient Alert Card.

 What if new information arises during this research trial?

Important new information about the medication being studied may become available during the course of the study.  If so, the study staff will notify participants and may need to discuss continuation of the trial or change some parts of the trial.

Can other medications be used during this trial?

While participants are taking the assigned medication for this trial, they might not be able to take some other medications, especially medications that affect blood clotting. Local doctors will discuss any medications which may need to be stopped, as well as any medication that should not be started while taking the study medication. Participants should always tell their study doctor about any changes to their medications or treatments during their participation in the trial.

Do people have to take part in this trial?

Participation in any research study is voluntary. If a person does not wish to take part they don’t have to. If they decide to take part and later change their mind, they are free to withdraw from the study at any stage.  Their decision whether to take part or not, or to take part and then withdraw, will not affect their treatment, and their relationship with local doctors and hospitals. If they choose not to participate, they will continue to receive usual medical care from their treating doctors.

What happens if participants withdraw from this trial?

Participants can choose at any time to withdraw from (take themselves out of) this trial. There is no need to give a reason for withdrawing from the trial. Their decision will not affect their usual medical care. If any participant chooses to withdraw from this trial, the study doctor and relevant study staff will not collect additional personal information, although personal information already collected will be retained to ensure that the results of the research project can be measured properly and to comply with law. Data collected up to the time of withdrawal will form part of the research project results.

 

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