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

Kidney Failure, Chronic Clinical Trial

— 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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03573089
• Other study ID #: 17.02
• Status: Recruiting
• Phase: N/A
• Start date: December 10, 2019
• Est. completion date: December 31, 2028

Study information

• Verified date: May 2023
• Source: The University of Queensland
• Contact: Ron Wald
• Phone: +1 416-867-3703
• Email: WaldR[@]smh.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3600
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hyperphosphatemia
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Liberal 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.
• Intensive 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.

Locations

Country	Name	City	State
Australia	Central and Northern Adelaide Renal and Transplant Service	Adelaide	South Australia
Australia	Armadale Hospital	Armadale	Western Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Bundaberg Hospital	Bundaberg	Queensland
Australia	Cairns Hospital	Cairns	Queensland
Australia	Royal Prince Alfred Hosptial	Camperdown	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Fraser Coast Renal Service	Hervey Bay	Queensland
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Mackay Hospital	Mackay	Queensland
Australia	Logan Hospital	Meadowbrook	Queensland
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	St Vincent's Hospital Melbourne	Melbourne	Victoria
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Latrobe Regional Hospital	Traralgon	Victoria
Australia	Western Sydney Renal Service	Westmead	New South Wales
Australia	Wollongong Hospital	Wollongong	New South Wales
Brazil	Sociedade Hospitalar Angelina Caron	Campina Grande	Paraíba
Brazil	Hospital de Clinicas Porto Alegre	Porto Alegre	Rio Grande Do Sul
Canada	Foothills Hospital/ U of Calgary	Calgary	Alberta
Canada	Alberta Health Services	Edmonton	Alberta
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	Queen's University	Kingston	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	The Charles Lemoyne Hospital	Longueuil	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	CHUM	Montréal	Quebec
Canada	Hopital Maisonneuve Rosemont	Montréal	Quebec
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Sacre Coeur Hospital	Montréal	Quebec
Canada	Oakville Trafalgar Memorial Hospital	Oakville	Ontario
Canada	Orillia Soldier's Memorial Hospital	Orillia	Ontario
Canada	Lakeridge Health	Oshawa	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	CHU de Quebec Universite Laval	Quebec City	Quebec
Canada	Scarborough Hospital Network	Scarborough	Ontario
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	St Michael's Hospital	Toronto	Ontario
Canada	St. Joseph's Healthcare Hamilton	Toronto	Ontario
Canada	St. Joseph's Healthcare Toronto	Toronto	Ontario
Canada	University Health Network - University of Toronto	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
New Zealand	Auckland City Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Waikato DHB	Hamilton
New Zealand	Hawkes Bay Hospital	Hastings
New Zealand	Middlemore Hospital	Otahuhu
New Zealand	Waitemata Hospital	Takapuna
New Zealand	Northland DHB	Whangarei
United Kingdom	NHS Lanarkshire	Airdrie	North Lanarkshire
United Kingdom	Wirral University Teaching Hospital NHS Foundation Trust	Birkenhead	Wirral
United Kingdom	Bradford Teaching Hospital NHS Foundation Trust	Bradford	West Yorkshire
United Kingdom	University Hospitals Sussex NHS Foundation Trust	Brighton	Sussex
United Kingdom	West Suffolk Hospital	Bury St Edmunds	Suffolk
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge	Cambridgeshire
United Kingdom	East Kent Hospitals University NHS Foundation Trust	Canterbury	Kent
United Kingdom	Gloucestershire Hospital NHS Foundation Trust	Cheltenham
United Kingdom	Dorset County Hospital NHS Foundation Trust	Dorchester	Dorset
United Kingdom	Royal Devon and Exeter NHS Foundation Trust	Exeter
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow	Kent
United Kingdom	James Paget University Hospitals NHS Foundation Trust	Great Yarmouth	Norfolk
United Kingdom	NHS Highland	Inverness	Scotland
United Kingdom	University Hospitals Of Leicester NHS Trust	Leicester
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	St George's University Hospitals NHS Foundation Trust	London
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United Kingdom	South Tees Hospitals NHS Foundation Trust	Middlesbrough	North Yorkshire
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham	Nottinghamshire
United Kingdom	University Hospitals Plymouth NHS Trust	Plymouth	Devon
United Kingdom	Royal Berkshire NHS Foundation Trust	Reading
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield	South Yorkshire
United Kingdom	Shrewsbury and Telford Hospital NHS Trust	Shrewsbury	Shropshire
United Kingdom	Mid and South Essex NHS Foundation Trust	Southend-on-Sea
United Kingdom	East and North Hertfordshire NHS Trust	Stevenage	Hertfordshire
United Kingdom	University Hospital of North Midlands NHS Trust	Stoke-on-Trent	Staffordshire
United Kingdom	South Tyneside And Sunderland NHS Foundation Trust	Sunderland	Durham
United Kingdom	York and Scarborough Teaching Hospitals NHS Foundation Trust	York	North Yorkshire

Sponsors (5)

Lead Sponsor	Collaborator
The University of Queensland	Applied Health Research Centre, Cambridge University Hospitals NHS Foundation Trust, National Health and Medical Research Council, Australia, University of Otago

Countries where clinical trial is conducted

Australia,  Brazil,  Canada,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Differences in the serum concentrations of phosphate, PTH, calcium, alkaline phosphatase and albumin		Time Frame: 5 years
Other	Phosphate-lowering medication usage		5 years
Other	Phosphate-lowering medication self-reported adherence		5 years
Other	Proportion of patients requiring parathyroidectomy		5 years
Other	Proportion of patients developing calciphylaxis		5 years
Other	Gastrointestinal Symptom Rating Scale	The Gastrointestinal Symptom Rating Scale (GSRS) is a 15-item instrument designed to assess the symptoms associated with common GI disorders. It has five subscales (reflux, diarrhea, constipation, abdominal pain and indigestion). Subscale scores range from 1-7 and higher scores represent higher symptom burden i.e. more discomfort.	5 years
Other	Itch/pruritus visual analog scale	The Pruritis 5-D scale contains five domains: duration, degree, direction, disability and distribution. The scores of each of the five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus).	5 years
Other	Cost-effectiveness analysis:	Difference in the incremental cost per Quality Adjusted Life Years gained	5 years
Primary	Time to a composite endpoint of cardiovascular death or non-fatal major cardiovascular event	Time to a composite endpoint of cardiovascular death, non-fatal myocardial infarction or coronary revascularization, stroke, or peripheral arterial event.	5 years
Secondary	Time to individual components of the primary composite endpoint,		5 years
Secondary	Time to all-cause death		5 years
Secondary	Utility-based quality of life EQ5D-5L	EQ5D-5L will be used to assess patient self-reported quality of life measures.	5 years

External Links

•   Australasian Kidney Trials Network Website