With a generous grant of just under £3.5million from Vifor Fresenius Medical Care Renal Pharma Ltd, Kidney Research UK facilitated the PIVOTAL trial (Proactive IV iron therapy in haemodialysis patients), which was led by King’s College Hospital, in partnership with Glasgow University Clinical Trials Unit. This ran from November 2013 to July 2018 and was one of the largest clinical trials in people with kidney disease undertaken in the UK to date, with 2,141 patients enrolled across 50 hospital renal units. 

Researchers compared two different clinical approaches: they gave one group of patients a high dose of iron (proactive high dose) and gave the other group the standard treatment of a low dose of iron only if their iron levels got too low (reactive low dose).   

Researchers found that giving patients a higher dose of iron was safe, effective, and better for treating anaemia in patients on haemodialysis than giving a lower dose. They found that patients had better outcomes on higher dose iron with reductions in clinical events such as heart attacks, strokes, hospitalisation for heart failure and death. The results of the trial were published in the New England Journal of Medicine in 2019.  

Heart failure and haemodialysis

Heart failure is a chronic condition where the heart is unable to pump blood around the body as effectively as it should. It is a common complication and one of the leading causes of death in kidney patients on haemodialysis. 

In a new paper, published in the Journal of the American College of Cardiology: Heart Failure, researchers have used data from the PIVOTAL trial to study the risk of developing heart failure in more detail. Dr Pardeep Jhund, lead author of the paper explains: “We wanted to look at the risk of developing heart failure in more detail because it is often difficult to diagnose and treat.” 

In this more detailed analysis, the team were able to look more thoroughly at the timing of heart failure events, understand more about how to predict which patients would suffer these events, and analyse the risk of death after hospitalisation from heart failure events, particularly within the first 30 days.  

A higher dose of iron cuts heart failure risk

These new results showed that a proactive higher dose of iron dramatically reduces the risk of heart failure in kidney patients on haemodialysis. “We found that the patients who received a higher dose of iron were 44% less likely to be hospitalised for heart failure,” said Pardeep. “This is important because patients who are hospitalised for heart failure are at very high risk of dying.” 

For patients who weren’t hospitalised for heart failure during the 4-year trial, their risk of death was 22%, compared with 56% for those who had been hospitalised with heart failure. And of those who had been hospitalised, 19% died within 30 days of being admitted. 

The researchers also found that patients who received a proactive higher dose of iron were less likely to have multiple hospital admissions for heart failure.  

The team discovered that patients who had suffered with heart failure complications previously, and patients with diabetes were most at risk of heart failure events. 

Dr Aisling McMahon, executive director of research, innovation and policy at Kidney Research UK, said, “We are hugely proud of everyone who helped to make the PIVOTAL trial happen, particularly the patients who volunteered to participate. This is the largest clinical trial we have ever coordinated and we are delighted to see that it is still providing results that will lead to improved treatments and better outcomes for kidney patients on dialysis.”  

Another author of the study, Professor Sunil Bhandari said: “Heart failure is a common and often deadly complication in patients receiving dialysis and this current evidence will we hope improve both the quality and length of life of our patients.” 

Find out more

Read the full paper here to find out more about the results. 

Find out more about how we are working to transform treatments for kidney patients.