Frequently Asked Questions
This information is for people in the UK. These are questions that you might have about the EMPA-KIDNEY Study (the Study of Heart and Kidney Protection with Empagliflozin). You can also download a copy of the Participant Information Leaflet and other study documents from the Downloads section.
Twenty years ago, a group of medications which block a biological system, called the renin-angiotensin system (RAS), were shown to protect the kidney and the heart. Because of these clinical trials, these medications are now widely used (and participants may be taking one: their names end in ‘–pril’ or ‘–sartan’). These simple treatments have meant some people have not needed to start dialysis and have saved lives.
However, despite taking RAS blockers, many people with kidney problems continue to develop worsening of their kidney disease and/or heart problems. Scientists are searching for new treatments to reduce the remaining risk of kidney and heart problems in people with kidney disease.
There is now a new medication called empagliflozin (pronounced em-pa-gli-FLOE-zin) which was originally developed to treat high blood sugar in people with diabetes, but has recently been shown to have beneficial effects on both the heart and kidney.
Empagliflozin causes blood sugar (equivalent to 10 teaspoons a day) to pass into the urine. It likely also increases the amount of salt (sodium) passing into the urine. This results in a modest fall in body weight and blood pressure.
Importantly, a large clinical trial has shown that empagliflozin reduces the number of deaths from heart disease in people who already have both heart disease and type 2 diabetes. Because of these results, empagliflozin is used in selected patients with diabetes around the world.
The same study suggested empagliflozin might reduce kidney problems. From the way we think the pills work, there is good reason to believe this new medication could benefit people who have kidney disease, whether they have diabetes or not.
Local doctors have reviewed existing blood and urine test results which show some evidence that invited individuals have protein in the urine or reduced kidney function in the past. Most people are probably already aware of this, but may not be, and it is also possible that the protein in the urine or reduced kidney function is no longer present.
Potential participants have therefore been invited to a study appointment to test their blood and urine again, and to discuss taking part in the study.
The scientists need a range of people to join the study, including those with only early signs of kidney disease risk as well as people who have already seen a kidney doctor.
Participants do not have to have diabetes to take part, in fact the study needs lots of people with and without diabetes to join.
For EMPA-KIDNEY to be able to give reliable results, it is important that people stay in the study and take their study pill every day for about 3-4 years, wherever possible.
The study needs to be this long so it is a definitive test of the effects of the pills on kidney disease which can take years to progress. The results of the study could have a major impact on how kidney patients around the world are treated.
By joining the study, we are asking participants to attend the study clinic 3 times in the first 6 months, and then attend every 6 months after that.
At each study appointment, a trained researcher (usually a nurse) will ask about participants' health and provide a new supply of study pills. A blood sample will be taken to monitor the kidneys and other effects of the study pills.
At a small number of visits, we will also ask participants to provide a urine sample.
With permission, we would also like to store left over blood and urine for future scientific research, including tests on genes. This part of the study is optional, so a person can still participate in the study if they do not want their left over blood and urine stored long-term.
No-one has to take part in this study. It is entirely the decision of each person invited. It is important to be aware that if a person joins this study, it will not affect any decisions about other medical treatment that might they might need or be receiving from their own doctors.
If a person does decide to come to the first study appointment they will be given an opportunity to ask questions about the study. Once we have rechecked the blood and urine tests, we will also check with the hospital doctor leading the study in the local hospital that they think the person is appropriate to join the study and we will also tell their GP that they wish to take part.
By joining this study, each participant will become part of our efforts to save the lives of people with kidney problems and hopefully reduce the need for kidney dialysis in years to come.
Half the people taking part in this study will get the empagliflozin pill and half will get the dummy inactive pill (known as placebo). Which treatment a participant gets will be decided by the computer by chance (like tossing a coin). This is called randomization.
Participants, and their doctors, will not know which treatment they have been given and the study staff will not know either. This ensures the study gives results which are reliable and trustworthy.
First appoIntment (Screening Visit)
At the first study appointment (called the Screening Visit), with participant agreement, a trained study nurse will check previous blood and urine test results and then explain the study. There will be plenty of time to ask questions.
Participants will then be asked to sign a Consent Form if they agree to take part.
The study nurse will then ask some more details about medical history and current medication. They will also take a fresh blood sample (about 1 teaspoonful) and collect a urine sample to be sent to the local laboratory for testing.
If a participant is willing and able to take part in EMPA-KIDNEY, the study research nurse will give them a supply of pills to take for 2-3 months to see if taking extra pills every day is acceptable.
The research team will write to and inform participants' GPs to let them know that they are planning to join the study.
This first appointment is the longest appointment and could take up to an hour to complete.
Second Appointment (Randomization Visit)
2-3 months after the first visit, will be the second appointment (called the Randomization Visit). At this appointment we will check how participants got on taking the study pills. They will also be asked if they remain willing to commit to the study for around 3-4 years.
If participants are happy to join, a study nurse will perform a short interview, collect another blood sample (about 6 teaspoons this time), ask for a urine sample, and give out the next set of study pills.
This appointment should only take 30-45 minutes to complete.
Other appointments (Follow-up Visits)
The next appointment (called a Follow-up Visit) will be 2 months after the Randomization Visit. After that appointment, the study research nurse will see participants 4 months later and then every 6 months.
At each Follow-up Visit, the study nurse will ask about any new medical problems since the last appointment, give the next supply of study pills and take a blood sample (between 3-6 teaspoons each time) and possibly a urine sample.
Each Follow-up Visit is designed to ideally take less than 30 minutes (although the time needed to collect blood samples and dispense study pills can vary from hospital to hospital).
Following the last study Follow-up Visit, participants will stop the study pills. About 4 weeks later, they will be asked to provide one further blood test (about 1 teaspoonful) and a urine sample.
This table gives a summary of what will happen at each appointment.
† Some Follow-up Visits only
We hope participants will be able to continue to take the study pills for the full course of the study.
For the study to produce reliable results, it is necessary both for participants to remember to take their study pills as best they can, and for the study team to collect complete information about the health of as many participants as possible.
Participation is voluntary. Each person has the right to decide they no longer wish to, or are no longer able to, participate in any aspect of the study at any time. All data as well as blood and urine samples already collected until the time of discontinuation will be kept and used as described.
If a participant withdraws, their usual rights as an NHS patient will not be affected in any way.
If a participant is asked to stop their study pills by a doctor, or choose to stop them themself, it would be very helpful if they would allow the study team to stay in touch. To make sure the study produces reliable results we would also need, wherever possible, to continue to collect blood samples at the study clinic for the full study duration (3-4 years).
A participant may decide that they no longer wish to come to the study clinic. What would happen in this case is described in more detail in the Data Protection section.
The amount of blood taken at appointments will vary at different times during the study but will usually be between 3 and 6 teaspoons of blood each time.
The blood samples provided will be used to measure things such as kidney, liver, heart function, and levels of blood sugar and salts in the body. The study team want to measure these things to assess the effects of the study pills.
The urine samples will be measured for protein markers of kidney disease and damage.
Some of these tests are not routinely performed by all hospitals, so some of the blood and urine will be transported to Oxford. This is why study blood and urine samples will need to be taken at the study appointments rather than at a GP’s surgery.
The study research nurse will also ask participants if they would allow left over blood and urine samples, together with health data collected in this study, to be stored long-term to help investigate other effects of empagliflozin and other future research.
Leftover blood and urine samples are those which have already been collected for the purposes of the study, and would be discarded otherwise. There is no additional health risk to participants.
Participants have the choice whether or not they would like to participate in this optional part of the study. If someone decides that they do not want to give permission, they can still take part in the main part of the study.
Doctors already know about some of the causes of kidney disease and heart disease. Scientists also think that other factors might play a part, but there is limited understanding of how they work.
In particular, we have limited knowledge about the effect of genes/DNA on the risks of kidney disease, heart disease, strokes, diabetes and a range of other health problems that might be linked to these diseases. These include diseases that doctors might refer to as metabolic, cardiovascular, infectious or malignant diseases.
If we have participants' permission to keep their samples, then in the years to come they might be able to make new scientific discoveries using both the information collected in the study and by defrosting and analysing samples (including testing some or all of participants' genes/DNA).
With participant consent, the blood/urine samples will be stored in a freezer overseen by the University of Oxford for up to 30-years after the study is completed, and will then be destroyed.
All blood and urine samples will be stored with a unique number, which means participants cannot be directly identified from them (i.e. they are “de-identified” from names and other written personal details).
Please note that much like fingerprints, it is theoretically possible to identify someone if their samples are genetically analyzed or if their samples are put together with other data about that person. But the chances of successful re-identification by someone without permission to do so are very low because we implement adequate organizational and security measures to protect participant data.
For this future research to happen we may need to share “de-identified” samples with laboratories outside Oxford which can perform specialized tests. Samples may also be sent to Boehringer Ingelheim1 to process, together with information collected in the study, for the research purposes described above.
Results from this research may also be shared with health regulators.
Please note that neither participants nor their doctors will be given any information from the analysis of blood and urine samples, including any details of genes/DNA. In particular, having these samples stored and tested will not affect the ability to get medical or life insurance.
1When we say Boehringer Ingelheim, in this case we mean it to also include Boehringer Ingelheim Group of Companies, who may work with other public or commercial private partnerships.
Participants may be helping themselves, but it is expected that the information from this study may help doctors and scientists to improve treatment for people who have kidney disease. If empagliflozin is shown to have benefits, results from this study may help to prevent deaths from heart disease and the need for dialysis or transplantation around the world.
Please note that participants are donating their time, information and blood/urine samples, for which we are grateful, but they or their relatives will not be able to receive any financial benefits from any discoveries or products developed using the results from this study or any future research using their health information and data.
Most treatments have side effects, which some people may experience, and others may not.
EMPA-KIDNEY is testing empagliflozin, which has already been tested in over 8,000 people. Among these people, it has been generally well-tolerated. It now has a licence from health regulators for use in some types of people who already have type 2 diabetes.
Nevertheless participants may experience some symptoms when taking empagliflozin which come from the way the drug works in the body. For example, empagliflozin causes increase salt and water loss into the urine and some people report noticing a need to pass urine more often. Some have reported symptoms suggestive of dehydration, such as increased levels of thirst or feeling faint. It may be necessary to change some of a participants other pills to compensate. Such symptoms (and other common symptoms) may also happen if participants are on the inactive pill (placebo), as they are common in people being treated for a kidney problem or diabetes.
For people with diabetes, there is a risk of a condition called ketoacidosis. If a potential participant has had ketoacidosis in the last 5 years they cannot join the study. Ketones build up if there is too little insulin in the body, a situation which also leads to persistently high levels of blood sugar. When taking empagliflozin, ketoacidosis can develop without blood sugar levels being particularly high. The symptoms of ketoacidosis are non-specific, including feeling or being sick, tummy ache and shortness of breath. Others may notice the smell of pear drops or nail varnish on the breath. Ketoacidosis is treated with increased insulin and fluid intake. Hospital treatment with a drip and insulin may be needed. There is extra information available on ketones in a separate information leaflet for those participants with diabetes.
As with all medicines, some people can develop an allergic reaction, including itchy skin or a skin rash. Very rarely, some people may require immediate treatment in a hospital or emergency room for swelling around the mouth and throat causing difficulty in breathing.
Local doctors may also notice that kidney function slightly decreases on starting empagliflozin. This may be transient and may not be a bad thing as it may be a sign of the protective effect of empagliflozin (or perhaps just natural changes in kidney function). They may also notice a slight increase in the concentrations of cholesterol and red blood cells in the blood.
Throughout the study, the research team will carefully monitor participants and their blood tests for possible side effects. Some side effects may necessitate study pills to be stopped temporarily or permanently.
The study research nurse will keep participants up to date with any new important information we learn about the pills.
If participants do experience unexpected symptoms and want to ask questions, they can contact their local study research nurse, or an EMPA-KIDNEY study doctor based in Oxford, on Freefone 0808 164 4060 (available 24 hours a day, 7 days a week).
Empagliflozin also works by increasing sugar in the urine. This can occasionally cause pain on passing urine and/or increase the chance of a urine or genital tract infection, like thrush. Confirmed infections are usually easily treated with a course of antibiotics or antifungal pills. If such treatment is ever needed, a GP or local study team could help diagnose and treat it.
Low blood sugar may also occur in people with diabetes who are already taking insulin or certain diabetes pills (like gliclazide). Common low blood sugar symptoms include: sweating, shakiness, hunger, restlessness, slurred speech, and confusion. A sugary drink normally reverses the problem.
Although empagliflozin does not appear to cross the placenta, it is possible empagliflozin could affect an unborn child. Women who are pregnant, plan to get pregnant or are breast-feeding cannot join the study. Women who could become pregnant must agree to use highly effective contraception throughout the study and for a week after the end of the study (types of contraception which are considered highly effective are listed in the footnote below2).
If a participant becomes pregnant during the study (or wishes to do so), they should stop taking the study pills and tell the local study nurse or study doctor promptly so appropriate action can be taken.
If participants have private medical insurance or require travel insurance, their policy may be affected by joining the study, they should check this with with their insurance provider.
2Highly effective methods of contraception include implants, injections, combined oral contraceptive pills (started at least 3 months before joining the study), intrauterine devices (often known as a coils), vasectomised partner, or true and complete abstinence (i.e. not calendar or temperature methods).
The results will be published in health or scientific journals, on websites (including ClinicalTrials.gov and www.clinicaltrialsregister.eu) and will be discussed at major conferences. Others will learn from the results, which we hope will show that more lives can be saved by using empagliflozin. No individual participant will be identified in any report or publication.
We will try our best to inform participants and their GPs of the study results, and any related publicity. We will use study newsletters and videos on the study’s website to inform people about what the study shows.
Participants' contribution to the study could be even more valuable if we have their permission to get information about their health after the very last study appointment. This way we can learn about any longer-term health effects of the study pills. This might include a questionnaire or phone call once a year. Also, the study scientists can continue to get information about participants' health, such as details from local doctors, NHS England (or other central NHS registry) and the UK Renal Registry.
Participants have all the usual rights of an NHS patient if they join the study or not.
The University of Oxford has arrangements in place to provide for harm arising from participation in the study. In the unlikely event of anyone being harmed by taking part, insurance cover is provided by the study sponsor Boehringer Ingelheim International GmbH. Any compensation would be paid in accordance with the guidelines of the Association of British Pharmaceutical Industry.
If participants have concerns about any aspect of the study they can speak with the EMPA-KIDNEY team by calling a 24-hour Freefone number: 0808 164 4060 (UK only). If they remain unhappy about the study in other ways and wish to complain formally, they can do this through the NHS Complaints Procedure. They can get details from their local hospital.
Participants can contact the EMPA-KIDNEY team if they have any questions.