IMPROVE-CKD TRIAL 

Cardiovascular disease (CVD) is the most common complication and cause of death in people with chronic kidney disease. High levels of phosphate, a mineral normally cleared by functioning kidneys, are a risk factor of CVD. Taking phosphate binder medication with food to bind phosphate in the diet, and reduce gut absorption, has long been a treatment for high phosphate levels in people with kidney disease.

Previous studies have examined the effect of phosphate binders on people on dialysis, and research has found lowering phosphate levels may be effective in reducing the risk factors for cardiovascular disease. However, to date there have been no studies that specifically look at the effect of lanthanum carbonate medication (a phosphate binder) on this CVD risk factor in chronic kidney disease patients who are not on dialysis. So, we developed a study to examine whether lanthanum carbonate could reduce the risk of heart disease, an area of keen interest to the nephrology community. 

The IMPROVE-CKD trial started in March 2012, and data collection finished in August 2019. We enrolled 278 adult participants with stage 3 or 4 chronic kidney disease across 18 hospitals in Australia, New Zealand and Malaysia. Half of participants received lanthanum carbonate for 96 weeks, and the other half received a placebo. This has been the longest and largest trial of its kind to date.

Over the 2-year study period, pulse wave velocity (a measure of stiffness of arteries) and CT scans (looking at calcium build up in arteries) were performed, medical information was collected, and blood samples were taken. 

The IMPROVE-CKD trial found lanthanum carbonate does not have a beneficial effect on aortic calcification (calcium in the main artery in the body, the aorta) or arterial stiffness, compared with a placebo.

When reviewing research results, it’s important to remember that they are only based on participants included in the trial. Other trials may provide new information or different results. So, determining which treatments work best for people is almost always the culmination of several trial results.

Some may consider a negative finding like this as less important than other trial results, but this information is still critical for Nephrologists to determine best treatment pathways for patients. The pill burden and economic impact for people with chronic disease is very high, and if we can show that certain treatments provide limited benefit, then that is just as important as finding something that works.

In addition to our main findings, there is still a lot of useful information being extracted and analysed from the data collection of the IMPROVE-CKD trial. The scientific and economic impact of large trials, which examine areas sometimes overlooked by pharmaceutical companies, are significant and of great interest to the medical profession.  

The main results of the IMPROVE-CKD trial have been published here in the Journal of the American Society of Nephrology.

The IMPROVE-CKD study was sponsored by The University of Queensland, coordinated by the Australasian Kidney Trials Network, and funded through research grants from the National Medical and Medical Research Council (NHMRC) and Shire International GmbH, a member of the Takeda group of companies.

Hospitals involved in the trial included: John Hunter Hospital, Westmead Hospital, Royal North Shore Hospital, Concord Repatriation and General Hospital, Logan Hospital, Princess Alexandra Hospital, Flinders Medical Centre, Royal Adelaide Hospital, Austin Health, Eastern Health, The Royal Melbourne Hospital (Melbourne Health), Western Health, North Shore Hospital, Dunedin Hospital, Hospital Sultanah Aminah Johor Bahru, Hospital Pulau Pinang, Hospital Tuanku Ja’afar Seremban and Universiti Kebangsaan Malaysia Medical Centre.

Professor Carmel Hawley is the Chair of the Executive Operations Secretariat of the Australasian Kidney Trials Network. 

Associate Professor Nigel Toussaint from The Royal Melbourne Hospital, co-led the trial with Professor Eugenia Pedagogos, from Melbourne’s Western Health. Professor Rob Walker from Dunedin Hospital, was the lead Investigator in New Zealand.

Dr. Hooi Lai Seong, was the lead investigator in Malaysia.

Image 1: Mohammed Haneefa Nizmudeen/iStock

Image 2: HYWARDS/iStock

Image 3: Mohammed Haneefa Nizmudeen/iStock