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Around three million people in the UK have kidney disease

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Iron trial results pave the way for improved haemodialysis Maria Thompson

29 January 2019

An update of the highly anticipated results of a Kidney Research UK facilitated clinical trial, designed to determine the optimum dose of IV iron for a kidney patient on haemodialysis, has been published in the New England Journal of Medicine (N Engl J Med 2019; 380:447-458).

Key research findings

  • The Proactive IV irOn Therapy in haemodiALysis patients (PIVOTAL) trial compared proactive, high-dose and reactive low-dose intravenous (IV) iron treatment in 2,141 UK haemodialysis patients;
  • Among these patients, who had recently started dialysis, high-dose intravenous iron administered proactively was better than a low-dose course administered reactively;
  • In the group of patients receiving high-dose iron, there was a significantly lower risk of death or major non-fatal cardiovascular events (such as heart attacks or heart failure), as compared to the low-dose group;
  • The group of patients receiving high-dose iron also required lower doses of erythropoiesis-stimulating agent (also known as EPO) and fewer blood transfusions.

Publication of the results in this prestigious, peer-reviewed medical journal signify the importance of the Proactive IV irOn Therapy in haemodiALysis patients (PIVOTAL) trial not just in the UK, but globally.

The trial demonstrated that a higher-dose of intravenous iron reduced the risk of death, hospitalisation for heart failure, and other major cardiovascular events, and reduced both erythropoietin (EPO) dose requirements and the need for blood transfusions in comparison to lower doses of iron.

There was also no increased infection risk in those receiving a higher dose of iron which is important, given previous research has suggested that iron might increase bacterial growth and infection.

The results explained

Have a look at our video in which research nurse, Elizabeth Clarke from Canterbury, explains the results:

Steering Committee member for the trial, Professor David Wheeler, said: “Intravenous iron is a routine part of anaemia management in haemodialysis patients worldwide. However, there has been little evidence to guide optimum dosing, and no consistency in approach across the UK or globally. The PIVOTAL trial was designed to address this shortfall in the evidence base, comparing proactive, high-dose and reactive low-dose intravenous iron treatment.

“PIVOTAL shows that patients treated with higher iron doses (who also received less EPO) experienced fewer cardiovascular events and no increase in serious adverse events when compared to those receiving lower doses.

“Clinicians use both EPO and iron to treat anaemia in haemodialysis patients. Giving more iron allows us to use less EPO. High doses of EPO have been associated with an increased risk of cardiovascular events, such as strokes. This is why clinicians like to minimise the EPO dose by giving more iron. The PIVOTAL trial provides reassurance that this is a good approach.”

Another outcome of the PIVOTAL trial is a reduction in the number of blood transfusions needed in those receiving high-dose iron. This is potentially positive news as blood transfusions can lead to the production of antibodies, which could increase the likelihood of kidney transplant rejection further down the line.

About the trial

Taking place exclusively in the UK, PIVOTAL was a randomised controlled trial which involved the collaboration of 50 doctors from 50 of the UK’s 80 renal units, along with over 50 research nurses and 2,141 kidney patients. It was led by King’s College Hospital, London in partnership with Glasgow University Clinical Trials Unit.

Professor Wheeler added: “PIVOTAL has demonstrated that the UK renal community can successfully deliver a large, randomised trial. The on-going enthusiasm, commitment and support shown by the participating sites has been a key factor in ensuring the success of this important study. We also need to thank all the patients who have taken part for many years. Their dedication to and participation in this landmark study has helped answer important questions about the treatment of haemodialysis patients with anaemia.”

“PIVOTAL has clarified a better approach to the treatment of anaemia in patients who have recently started haemodialysis.”

It is anticipated the results of PIVOTAL will lead to a review of national and international clinical practice guidelines.

Kidney Research UK has been instrumental in organising the collaboration required in this four-and-a-half year trial.

Kidney Research UK chief executive Sandra Currie said: “This is the first trial of its kind and one of the largest to have taken place in the UK dialysis population and we are immensely proud of everyone who took part and helped to make it happen. It brought together patients and clinical staff from right across the country to understand how we can improve the clinical care of patients on dialysis.

“This has been a huge project for the charity to facilitate and we are delighted to see it has yielded positive results. There was a gap in the understanding of intravenous iron therapy which needed to be addressed and we now believe that the results will lead to improved treatments and better outcomes for patients.”

The charity was supported by an unrestricted grant of just under £3.5million from Vifor Fresenius Medical Care Renal Pharma Ltd. The company also provided all the iron for the study, free of charge.

These results supersede those published on The New England Journal of Medicine website on 26 October 2018. The updated results can be viewed on: www.nejm.org/doi/full/10.1056/NEJMoa1810742

In the UK alone, there are 25,000 people on haemodialysis; 3,000 people die on dialysis every year.

Kidney patients on dialysis are deficient in iron because they lose more iron than they absorb from the gut. Added to this, their kidneys no longer produce enough of the red blood cell-forming hormone, EPO.

All patients are given iron intravenously via their dialysis machines because iron tablets don’t work for them.

The experience of a patient on the trial

Derek King a Pivotal trial patient
Derek King a Pivotal trial patient

Derek King (84), of Romney Marsh, was one of the patients who took part in the trial. It formed part of his regular four-hour haemodialysis sessions, held three times a week at the Canterbury Renal Unit.

Derek said: “I consider myself fortunate. I’ve lived my life and don’t have to rush around anymore, but some of the younger people on dialysis have got school work, jobs or young families to think of.

Hopefully their lives will improve as a result of this trial.”

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