Pragmatic randomised trial of High Or Standard PHosphAte Targets in End-stage kidney disease
Principal Investigators: Sunil Badve
Clinical Project Manager: Liza Vergara (AKTN), Laura Robison (AKTN)
Clinical Research Associate: Peta-Anne Paul-Brent
Trial Number: AKTN 17.02
Population: ESKD patients on dialysis >45 years or >18 years with diabetes in Australia, New Zealand, Canada and UK.
Intervention: Intensive and liberal target phosphate level
Follow-up: 5 years
Primary outcome: Composite of major cardiovascular events
Status: Recruitment to commence 2nd Q 2019
Target Recruitment: 3,600 participants (600 in Australia and New Zealand)
Although hyperphosphatemia is associated with increased mortality risk in ESKD patients, the KDIGO Guidelines suggestion of ‘lowering elevated phosphate levels towards the normal range’ is based on low quality evidence. Phosphate- lowering medications, the mainstay of phosphate-lowering treatment, are associated with substantially increased pill burden and non-adherence, adverse gastrointestinal symptoms, poor quality of life; and are extremely expensive. However, RCT evidence demonstrating that treatments that lower serum phosphate will improve patient-centred outcomes, such as survival and how patients feel or function, is still lacking. Currently available evidence demonstrates only an association and not a cause-effect relationship between phosphate and clinical outcomes in patients with ESKD.
A recent editorial justly asked “How can a medication class achieve 75% prevalence of use in a chronic disease population without evidence of clinical benefit”; and concluded that “Clinical trials of phosphate binders are the only way to determine the potential benefits and harms of these commonly used and expensive medications”. Therefore, an adequately powered RCT is urgently required to evaluate whether reduction of serum phosphate concentration toward the normal level with phosphate-lowering medications reduces the risk of cardiovascular death or non-fatal major cardiovascular events; improves physical health, fatigue, and patient satisfaction in ESKD patients receiving dialysis; and is cost-effective.