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

The University of Queensland

Status: Enrolling

Conditions: Hyperphosphatemia; Kidney Failure, Chronic

Treatments: Drug: Liberal phosphate target; Drug: Intensive phosphate target

Study type: Interventional

Funder types: Other

Identifiers

NCT03573089

AKTN 17.02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3,600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,600 participants in 2 patient groups

Liberal phosphate target

Active Comparator group

Description:

Liberal serum phosphate target of 2.0 to 2.5 mmol/L.

Treatment:

Drug: Liberal phosphate target

Intensive phosphate target

Experimental group

Description:

Intensive serum phosphate target of ≤1.50 mmol/L.

Treatment:

Drug: Intensive phosphate target