Pragmatic Randomised Trial of High Or Standard PHosphAte Targets in End-stage Kidney Disease (PHOSPHATE) (PHOSPHATE)
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|ClinicalTrials.gov Identifier: NCT03573089|
Recruitment Status : Not yet recruiting
First Posted : June 29, 2018
Last Update Posted : March 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Kidney Failure, Chronic Hyperphosphatemia||Drug: Liberal phosphate target Drug: Intensive phosphate target||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||3600 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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.|
|Estimated Study Start Date :||July 1, 2019|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2025|
Active Comparator: Liberal phosphate target
Liberal serum phosphate target of 2.0 to 2.5 mmol/L.
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.
Experimental: Intensive phosphate target
Intensive serum phosphate target of ≤1.50 mmol/L.
Drug: 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.
- Time to a composite endpoint of cardiovascular death or non-fatal major cardiovascular event [ Time Frame: 5 years ]Time to a composite endpoint of cardiovascular death, non-fatal myocardial infarction or coronary revascularization, stroke, or peripheral arterial event.
- Time to individual components of the primary composite endpoint, [ Time Frame: 5 years ]
- Time to all-cause death [ Time Frame: 5 years ]
- Utility-based quality of life EQ5D-5L [ Time Frame: 5 years ]EQ5D-5L will be used to assess patient self-reported quality of life measures.
- Differences in the serum concentrations of phosphate, PTH, calcium, alkaline phosphatase and albumin [ Time Frame: Time Frame: 5 years ]
- Phosphate-lowering medication usage [ Time Frame: 5 years ]
- Phosphate-lowering medication self-reported adherence [ Time Frame: 5 years ]
- Proportion of patients requiring parathyroidectomy [ Time Frame: 5 years ]
- Proportion of patients developing calciphylaxis [ Time Frame: 5 years ]
- Gastrointestinal Symptom Rating Scale [ Time Frame: 5 years ]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.
- Itch/pruritus visual analog scale [ Time Frame: 5 years ]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).
- Cost-effectiveness analysis: [ Time Frame: 5 years ]Difference in the incremental cost per Quality Adjusted Life Years gained
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03573089
|Contact: Ron Wald||+1 416-867-3703||WaldR@smh.ca|
|Contact: Thomas Hiemstra||+44 1223 3 firstname.lastname@example.org|
|Principal Investigator:||Sunil Badve||The University of Queensland|
|Principal Investigator:||Ron Wald||St. Michael's Hospital, Toronto|
|Principal Investigator:||Thomas Hiemstra||University of Cambridge|