UK Heart and Renal Protection (UK HARP-III)

Plain English Summary

Background and study aims
Chronic kidney disease affects about 1 in 10 adults. The illness can worsen over time. This means that some people eventually need to have dialysis or a kidney transplant. There are treatments that can slow the rate of decline of kidney function . However, despite such treatment some people still need transplantation or dialysis. The aim of the study is to investigate whether a new drug (LCZ696) has the potential to protect the kidneys better than the current standard treatment.

Who can participate?
Men and women aged 18 and over with chronic kidney disease who have increased levels of protein in their urine.

What does the study involve?
You will need to participate in the study for about 13 months. You will be asked to attend about seven hospital appointments, some of which may coincide with your routine renal outpatient appointments. In addition, we will measure your kidney function very precisely on two occasions during the study. At your first visit to the clinic a trained researcher (usually a nurse) will ask you about your medical history. The researcher will take your blood pressure and a sample of blood and urine. You will then be provided with a supply of the study tablets and asked to take two a day. This visit will take about 45 minutes. You may be asked to stop some of your current blood pressure treatment (because the study treatment will replace them). Over the course of the next few weeks you will have the chance to try out the study tablets. This will allow you and the study doctors and nurses to be sure the routine of taking these particular tablets agrees with you. Towards the end of this period you may be asked to collect your urine for 24 hours, but this is optional and you can still participate even if you don’t want to do this. After at least 4 weeks of taking the study tablets you will be asked to attend a second appointment to see if you would like to continue. We will measure your kidney function and your blood pressure and we will ask for another blood and urine sample. Your height and weight will also be recorded at this visit. If you have had no problems with the study treatments during the first few weeks and are happy to continue, you will be asked to commit to the study for another 12 months. This visit will take about 30 minutes. Following this appointment you will take two different tablets once daily: an active tablet and a placebo (dummy) tablet. You will be randomly allocated to take either active LCZ696 and placebo irbesartan, or placebo LCZ696 and active irbesartan. Irbesartan is an angiotensin receptor blocker and is commonly used to treat kidney disease. At further visits you will be asked to have a blood test after about two weeks to check your potassium level. This can be done at your GP surgery or your kidney clinic. The dose of your study treatment will then increase to the full dose (two tablets of active treatment and two tablets of placebo once daily).You will be asked to attend five further appointments (about 1, 3, 6, 9 and 12 months later) to see how you are getting on. Your blood pressure will be checked and a blood and urine sample will be taken at each visit. At the final visit you will have a second measurement of your kidney function. Each visit will last about 30 minutes.

What are the possible benefits and risks of participating?
You may be helping yourself, but you will most certainly be helping doctors and scientists improve treatment for people who have chronic kidney disease and who may be at risk of needing dialysis or a transplant. If successful, results from this study will help to design a larger trial of LCZ696 which could reliably show whether LCZ696 is better than current treatment in slowing the progression of chronic kidney disease. Most treatments have side effects which some people may experience and others do not. If you do experience any side effects while on the study they will be noted, so that scientists can learn from you. You can withdraw from the study if you wish. Irbesartan is generally very well-tolerated. It has been tested in thousands of people and is taken by hundreds of thousands of people worldwide. It lowers blood pressure so it can cause dizziness. Other side effects include nausea, muscle pain and fatigue. It can raise potassium levels in the blood and you will be monitored for this. Over 8,000 people have taken LCZ696 in other clinical trials and it is generally well-tolerated. It also lowers blood pressure so can cause dizziness and fatigue. Rarely it may cause swelling of the mouth and face. The treatment can raise potassium levels in the blood and you will be monitored for this. One patient who received LCZ696 had an allergic reaction which included abnormal liver function tests. At this stage, scientists cannot rule out the possibility of there being side effects (such as diarrhoea or muscle pains), or effects on other blood tests. Throughout the study you will be carefully monitored by our nursing team for possible side effects. At every visit, the study staff would discuss any new information about the drug with you. The study includes two measurements of your kidney function which involve an injection of a small amount of radioactive material. The dose of radioactivity is small (equivalent to one day of natural background radiation in the UK) and poses a negligible risk to health.

Where is the study run from?
The study is coordinated by the Clinical Trial Service Unit at the University of Oxford. There will be about 20 centres taking part around the UK.

When is the study starting and how long is it expected to run for?
The study will start in early 2014 and last for about one year. Participants will be recruited during the first 6 months and follow-up in the study is for 12 months.

Who is funding the study?
Novartis AG Pharma (UK)

Who is the main contact?
Dr Richard Haynes

Study website

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• United Kingdom

Study participating centres

Sponsor information

University of Oxford (UK)
University/education

University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom

Phone	+44 (0)1865 270000
Email	harp3@ctsu.ox.ac.uk
Website	http://www.ox.ac.uk
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Industry

Results and Publications

Study outputs

Additional files

ISRCTN11958993_BasicResults_14Mar2018.pdf

Uploaded 09/05/2018

Editorial Notes

16/07/2018: Publication reference added.
09/05/2018: Publication reference, publication and dissemination plan and IPD sharing statement added. The basic results of this trial have been uploaded as an additional file.

03/05/2016: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/02/2014 to 01/11/2014.
2. The overall trial end date was changed from 31/01/2015 to 01/03/2017.
3. The target number of participants was changed from 360 to 400.