Pragmatic Randomised Trial of High Or Standard PHosphAte Targets in End-stage Kidney Disease (PHOSPHATE)

Not Applicable

Recruiting

• Conditions: Hyperphosphatemia; Kidney Failure, Chronic
• Interventions: Drug: Intensive phosphate target; Drug: Liberal phosphate target

• Registration Number: NCT03573089
• Lead Sponsor: The University of Queensland

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.

Study Timeline

• Study First Submitted: 2018-05-20
• Study First Submitted QC: 2018-06-18
• Study First Posted: 2018-06-29
• Study Start: 2019-12-10
• Status Verified: 2024-09
• Last Update Submitted: 2025-06-29
• Last Update Posted: 2025-07-01
• Primary Completion: 2027-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3600

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive phosphate target	Intensive phosphate target	Intensive serum phosphate target of ≤1.50 mmol/L.
Liberal phosphate target	Liberal phosphate target	Liberal serum phosphate target of 2.0 to 2.5 mmol/L.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Utility-based quality of life EQ5D-5L	5 years	EQ5D-5L will be used to assess patient self-reported quality of life measures.
Time to individual components of the primary composite endpoint,	5 years
Time to all-cause death	5 years

Trial Locations

Locations (115)

Royal Prince Alfred Hosptial; 🇦🇺 Camperdown, New South Wales, Australia

Nepean Hospital; 🇦🇺 Kingswood, New South Wales, Australia

St George Hospital; 🇦🇺 Kogarah, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 Saint Leonards, New South Wales, Australia

Western Sydney Renal Service; 🇦🇺 Westmead, New South Wales, Australia

Wollongong Hospital; 🇦🇺 Wollongong, New South Wales, Australia

Sunshine Coast University Hospital; 🇦🇺 Birtinya, Queensland, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

Bundaberg Hospital; 🇦🇺 Bundaberg, Queensland, Australia

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