STOP-ACEi
Research type
Research Study
Full title
Multi-centre Randomised Controlled Trial of Angiotensin Converting Enzyme inhibitor (ACEi) / Angiotensin Receptor Blocker (ARB) withdrawal in advanced renal disease; The STOP-ACEi Trial
IRAS ID
138827
Contact name
Sunil Bhandari
Contact email
Sponsor organisation
HEY NHS Trust
Eudract number
2013-003798-82
ISRCTN Number
62869767
Research summary
Research Summary
Chronic kidney disease (CKD) affects 1 in 10 adults in the UK and describes progressive loss of kidney function regardless of the original kidney disease. CKD can have serious implications for those affected, including a risk of CKD progressing to complete kidney failure so that replacement of kidney function by dialysis or transplantation is required. Kidney disease is expensive with a high proportion of the health-care budget spent on CKD; the cost of dialysis alone is ~£30,000/year. Patient quality of life can be poor, with dialysis leading to early death. Treating high blood pressure (BP) is the most important intervention that can slow CKD progression . Some people with CKD gain additional protection from Angiotensin Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARBs). These drugs treat high BP but also slow CKD progression by other means.
However recent research suggests that in some people with advanced CKD (stages 4 & 5) who are progressing to complete kidney failure and are receiving treatment with an ACEi and/or ARB, stopping these drugs leads to stabilization and improvement of kidney function and decreases or delays the need for dialysis. This indicates that in some patients the very tablets used to protect the kidneys may be contributing to a harmful decline in their function by some currently unknown mechanism.
To date, research on this is observational and a study to confirm the association between stopping these drugs and stabilisation of kidney function is required. In the STOP-ACEi trial we will randomly allocate suitable participants to either continue or stop their ACEi/ARB treatment and follow-up participants for 3-years. This study is needed before this treatment strategy can be put into routine clinical practice. In addition we will look at other effects of stopping these drugs such as cardiovascular effects and participant quality of life.
Summary of Results
Drugs called Angiotensin Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARBs), together known as Renin Angiotensin System (RAS) inhibitors, are used to treat high blood pressure, slow worsening kidney function, and lower the risk of kidney failure (known as end-stage kidney disease (ESKD) which requires treatment with dialysis or kidney transplantation) in patients with early chronic kidney disease (CKD). However, we did not know if patients treated with RAS inhibitors and who have progressed to more advanced CKD (stage 4 or stage 5) should stop or continue RAS inhibitors.
To determine whether stopping RAS inhibitors in people with advanced CKD leads to an improvement or stabilisation of kidney function required a study comparing the outcomes of people who had had these drugs stopped with a group who continued these drugs (The STOP-ACEi Trial). We recruited 411 participants with advanced CKD who were receiving RAS inhibitors from 37 kidney units in the United Kingdom, and randomly (like flipping a coin) allocated them to either stop or continue RAS inhibitors.
We then compared kidney function between the two groups at three years. We also assessed whether stopping or continuing RAS inhibitors had an influence on the development of ESKD or need for kidney replacement therapy, the number of hospitalisations, blood pressure, quality of life and physical function. We collected data on safety outcomes including death and heart related events (such as heart attacks).
The results of the trial showed no difference in kidney function at three years. The number of participants requiring dialysis, or a kidney transplant was also similar, as was the quality of life and physical function between the groups. Deaths and the number of heart event were similar in both groups.
This research suggests that it is safe to continue RAS inhibitors in patients with advanced CKD.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
13/YH/0394
Date of REC Opinion
29 Jan 2014
REC opinion
Further Information Favourable Opinion