Clinical trial NCT03573089: Pragmatic Randomised Trial of High Or Standard PHosphAte Targets in End-stage Kidney Disease (PHOSPHATE)
Official title: An Investigator-initiated, International, Multi-centre, Prospective, Randomized, Open-label, Parallel-group, Superiority, and Pragmatic Large Simple Trial (LST) to Determine Whether the Currently Recommended Strategy of Intensive Reduction of Serum Phosphate Concentration Towards the Normal Level Results in Significant Patient-centred Benefits in End-stage Kidney Disease (ESKD) Patients Receiving Dialysis.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Kidney Failure, Chronic
Hyperphosphatemia
Keywords: Renal dialysis
Randomised controlled trial
Bone markers
Cardiovascular risk factors
Phosphate lowering agent
End stage kidney disease
Hyperphosphatemia
Lead sponsor: The University of Queensland
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Applied Health Research Centre
name: Cambridge University Hospitals NHS Foundation Trust
name: University of Otago
First posted: 2018-06-29
Enrollment: 3600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to a composite endpoint of cardiovascular death or non-fatal major cardiovascular event
timeFrame: 5 years
Secondary outcomes:
measure: Time to individual components of the primary composite endpoint,
timeFrame: 5 years
measure: Time to all-cause death
timeFrame: 5 years
measure: Utility-based quality of life EQ5D-5L
timeFrame: 5 years
Other outcomes:
measure: Differences in the serum concentrations of phosphate, PTH, calcium, alkaline phosphatase and albumin
timeFrame: Time Frame: 5 years
measure: Phosphate-lowering medication usage
timeFrame: 5 years
measure: Phosphate-lowering medication self-reported adherence
timeFrame: 5 years
measure: Proportion of patients requiring parathyroidectomy
timeFrame: 5 years
measure: Proportion of patients developing calciphylaxis
timeFrame: 5 years
measure: Gastrointestinal Symptom Rating Scale
timeFrame: 5 years
measure: Itch/pruritus visual analog scale
timeFrame: 5 years
measure: Cost-effectiveness analysis:
timeFrame: 5 years
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hosptial
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Western Sydney Renal Service
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Royal Brisbane and Women&#39;s Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bundaberg
country: Australia
facility: Bundaberg Hospital
state: Queensland
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: Hervey Bay
country: Australia
facility: Fraser Coast Renal Service
state: Queensland
city: Mackay
country: Australia
facility: Mackay Hospital
state: Queensland
city: Meadowbrook
country: Australia
facility: Logan Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Townsville
country: Australia
facility: Townsville University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Central and Northern Adelaide Renal and Transplant Service
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent&#39;s Hospital Melbourne
state: Victoria
city: Traralgon
country: Australia
facility: Latrobe Regional Hospital
state: Victoria
city: Armadale
country: Australia
facility: Armadale Hospital
state: Washington
city: Campina Grande
country: Brazil
facility: Sociedade Hospitalar Angelina Caron
state: Paraíba
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas Porto Alegre
state: Rio Grande Do Sul
city: Barro Preto
country: Brazil
facility: Fundacao Felice Rosso - Hospital Felicio Rocho
city: São Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: Calgary
country: Canada
facility: Foothills Hospital/ U of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Alberta Health Services
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: Kingston
country: Canada
facility: Queen's University
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Oakville
country: Canada
facility: Oakville Trafalgar Memorial Hospital
state: Ontario
city: Orillia
country: Canada
facility: Orillia Soldier's Memorial Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Hospital Network
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - University of Toronto
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Healthcare Toronto
state: Ontario
city: Longueuil
country: Canada
facility: The Charles Lemoyne Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montréal
country: Canada
facility: Hopital Maisonneuve Rosemont
state: Quebec
city: Montréal
country: Canada
facility: CHUM
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: Sacre Coeur Hospital
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec Universite Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Red Deer
country: Canada
facility: Red Deer Hospital;
city: Toronto
country: Canada
facility: Humber River Hospital
city: Toronto
country: Canada
facility: Michael Garron Hospital
city: Toronto
country: Canada
facility: Trillium Health Partners
city: Paris
country: France
facility: Aura Paris
city: Jerusalem
country: Israel
facility: Hadassah University
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Centre
city: Kfar Saba
country: Israel
facility: Meir Hospital
city: Ramat Gan
country: Israel
facility: Sheba Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato DHB
city: Hastings
country: New Zealand
facility: Hawkes Bay Hospital
city: Otahuhu
country: New Zealand
facility: Middlemore Hospital
city: Takapuna
country: New Zealand
facility: Waitematā Hospital
city: Whangarei
country: New Zealand
facility: Northland DHB
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
state: Khet Ratchathewi
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: Cambridgeshire
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
state: Devon
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital NHS Foundation Trust
state: Dorset
city: Sunderland
country: United Kingdom
facility: South Tyneside And Sunderland NHS Foundation Trust
state: Durham
city: Stevenage
country: United Kingdom
facility: East and North Hertfordshire NHS Trust
state: Hertfordshire
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University NHS Foundation Trust
state: Kent
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
state: Kent
city: Great Yarmouth
country: United Kingdom
facility: James Paget University Hospitals NHS Foundation Trust
state: Norfolk
city: Airdrie
country: United Kingdom
facility: NHS Lanarkshire
state: North Lanarkshire
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust
state: North Yorkshire
city: York
country: United Kingdom
facility: York and Scarborough Teaching Hospitals NHS Foundation Trust
state: North Yorkshire
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
state: Nottinghamshire
city: Inverness
country: United Kingdom
facility: NHS Highland
state: Scotland
city: Shrewsbury
country: United Kingdom
facility: Shrewsbury and Telford Hospital NHS Trust
state: Shropshire
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
state: South Yorkshire
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospital of North Midlands NHS Trust
state: Staffordshire
city: Bury St Edmunds
country: United Kingdom
facility: West Suffolk Hospital
state: Suffolk
city: Brighton
country: United Kingdom
facility: University Hospitals Sussex NHS Foundation Trust
state: Sussex
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospital NHS Foundation Trust
state: West Yorkshire
city: Birkenhead
country: United Kingdom
facility: Wirral University Teaching Hospital NHS Foundation Trust
state: Wirral
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Hospital NHS Foundation Trust
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust
city: Leicester
country: United Kingdom
facility: University Hospitals Of Leicester NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
city: Reading
country: United Kingdom
facility: Royal Berkshire NHS Foundation Trust
city: Southend-on-Sea
country: United Kingdom
facility: Mid and South Essex NHS Foundation Trust
Study officials:
affiliation: The University of Queensland
name: Sunil Badve
role: PRINCIPAL_INVESTIGATOR
affiliation: St Michael&amp;#39;s Hospital
name: Ron Wald
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cambridge
name: Rona Smith
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Otago
name: Suetonia Green
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Glasgow
name: Patrick Mark
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Queensland
name: Rathika Krishnasamy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hamilton Centre for Kidney Research
name: Michael Walsh
role: PRINCIPAL_INVESTIGATOR
References: