Hyperphosphatemia, Kidney Failure, Chronic
Conditions
Keywords
Renal dialysis, Randomised controlled trial, Bone markers, Cardiovascular risk factors, Phosphate lowering agent, End stage kidney disease, Hyperphosphatemia
Brief summary
During end-stage kidney disease, clinical guidelines suggest reducing elevated phosphate levels in the blood. However, the effect of lowering blood phosphate levels on important patient-centred outcomes has never been tested. This trial will evaluate whether compared to high levels, lowering blood phosphate levels would reduce death or major events due to heart disease, improve physical health, and be cost-effective.
Detailed description
Hyperphosphataemia is highly prevalent in patients with end-stage kidney disease (ESKD) and associated with increased mortality risk. The Clinical Practice Guidelines suggest lowering elevated phosphate levels towards the normal range (level 2C suggestion). However, trial data demonstrating that treatments that lower serum phosphate will improve patient-centred outcomes are lacking. The primary objective is to test the hypothesis that compared to a liberal serum phosphate concentration target of 2.0 to 2.5 mmol/L, intensive lowering of serum phosphate towards the normal level (≤1.50 mmol/L) with phosphate binders reduces the risk of fatal or non-fatal major cardiovascular events in ESKD patients receiving dialysis. The secondary objectives are to test the hypothesis that intensive lowering of serum phosphate towards the normal level with phosphate binders would improve physical health, fatigue, health-related quality of life, patient satisfaction, and pruritus; and be cost-effective. In this pragmatic, multinational, randomised controlled large simple trial, a total of 3600 adult ESKD patients receiving dialysis will be randomised either to intensive (≤1.50 mmol/L) or liberalized (2.0-2.5 mmol/L) serum phosphate target. The choice and dose of phosphate binders will be at the treating physician's discretion and local practice to achieve and maintain serum phosphate concentration within the required target range according to randomisation. The primary endpoint is the composite endpoint of cardiovascular death, non-fatal major cardiovascular or peripheral arterial events. The secondary outcome measures will be individual components of the primary composite endpoint, all-cause death, and utility-based quality of life EQ5D-5L.
Interventions
DRUGLiberal phosphate target
All phosphate-lowering medications in use at baseline will be discontinued. Phosphate-lowering medications will be prescribed only if serum phosphate concentration exceeds 2.50 mmol/L. The choice and dosages of phosphate-lowering medications will be at the discretion of treating physicians and/or participants.
DRUGIntensive phosphate target
This will be achieved by prescribing phosphate-lowering medications aimed to intensively lower serum phosphate concentration towards normal level (≤1.50 mmol/L). The choice and dosages of phosphate-lowering medications will be at the discretion of treating physicians and/or participants.
Sponsors
The University of Queensland
National Health and Medical Research Council, Australia
Applied Health Research Centre
Cambridge University Hospitals NHS Foundation Trust
University of Otago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥45 years, or Age ≥18 years with diabetes, 2. ESKD on haemodialysis or peritoneal dialysis, for at least 3 months, 3. Currently prescribed at least one phosphate-lowering medication at any dose 4. Able to provide informed consent
Exclusion criteria
1. Elective kidney transplantation scheduled, 2. Concomitant major illness / comorbidity that may result in death in the next 6 months in the view of the treating physician, 3. Participation in an interventional study that is likely to affect serum phosphate concentration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to a composite endpoint of cardiovascular death or non-fatal major cardiovascular event | 5 years | Time to a composite endpoint of cardiovascular death, non-fatal myocardial infarction or coronary revascularization, stroke, or peripheral arterial event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to individual components of the primary composite endpoint, | 5 years | — |
| Time to all-cause death | 5 years | — |
| Utility-based quality of life EQ5D-5L | 5 years | EQ5D-5L will be used to assess patient self-reported quality of life measures. |
Countries
Australia, Brazil, Canada, France, Israel, New Zealand, Singapore, Thailand, United Kingdom
Contacts
CONTACTRon Wald
CONTACTRona Smith
PRINCIPAL_INVESTIGATORSunil Badve
University of New South Wales
PRINCIPAL_INVESTIGATORRon Wald
Unity Health Toronto
PRINCIPAL_INVESTIGATORRona Smith
University of Cambridge
PRINCIPAL_INVESTIGATORSuetonia Green
University of Otago
PRINCIPAL_INVESTIGATORPatrick Mark
University of Glasgow
PRINCIPAL_INVESTIGATORRathika Krishnasamy
The University of Queensland
PRINCIPAL_INVESTIGATORMichael Walsh
Hamilton Centre for Kidney Research
Outcome results
None listed