Two phosphAte taRGets in End-stage Renal Disease Trial (TARGET)

Study Overview
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Brief Summary
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Patients with end-stage renal disease (ESRD) who have elevated serum phosphate (P) levels have significantly higher mortality rates compared to those with normal P. In patients receiving conventional dialysis regimens, serum P may be lowered through dietary intervention and use of P binders, though these have potentially important side effects and may adversely impact quality of life. Whether lowering P, and / or targeting specific P levels improve survival and clinical outcomes is unknown. Despite this uncertainty, over 90% of patients with ESRD receive P lowering therapy and guidelines for the care of patients with ESRD are increasingly calling for more aggressive phosphate lowering. This intensive P lowering results in extra medications (and their associated side-effects), and higher health care costs. We are uncertain whether the intensification of P control results in measurable benefits to patients with ESRD. The overall goal of this pilot trial is to evaluate the feasibility of conducting a randomized controlled trial of intensive vs liberalized phosphate control among hemodialysis recipients.

Official Title
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Two phosphAte taRGets in End-stage Renal Disease Trial (TARGET): Intensive vs Liberalized Phosphate Control in Hemodialysis Recipients

Conditions
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End-stage Renal Disease

Intervention / Treatment
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* Drug: Calcium carbonate ( Intensive phosphate control)
* Drug: Calcium carbonate (Liberalized phosphate control)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 yrs Receiving chronic hemodialysis for > 90 days, Dialysis prescription is currently no more than 4 sessions per week and prescribed as 3-5 hrs per session Most recent P value 1.30-2.50 mmol/L Receipt of a calcium-based P binder Exclusion Criteria: Patient is booked (with a known surgical date) for a live donor kidney transplant in the next 26 weeks Planned switch to a dialysis schedule that involves > 16 hours per week of therapy within the next 26 weeks. Planned switch to peritoneal dialysis within the next 26 weeks Pregnancy Albumin-corrected serum calcium > 2.60 mmol/L in the past year requiring reduction of the calcium carbonate dose History of calciphylaxis Attending nephrologist believes that an otherwise eligible patient is mandated- on clinical grounds- to have a P value that is targeted to < 1.50 mmol/L or > 2.00 mmol/L Attending nephrologist believes an otherwise eligible patient is not a candidate for escalation of the current calcium dose Co-enrollment in a clinical trial where the intervention is deemed to interfere with the adherence, safety or efficacy of the intervention provided herein

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive phosphate control<br>Individuals randomized to this arm will be exposed to a treatment strategy that targets a P of < 1.50 mmol/L, reflecting the recommendations of current guidelines. Titration of the calcium carbonate dose will be the core of this approach and this will be complemented by usual recommendations regarding dietary P restriction. Dietitians will be available to provide counseling with regards to any aspect of the end-stage renal disease diet, as per usual dialysis unit practice. | Drug: Calcium carbonate ( Intensive phosphate control)<br>* Individuals randomized to this arm will be exposed to a treatment strategy that targets a P of < 1.50 mmol/L, reflecting the recommendations of current guidelines. Titration of the calcium carbonate dose will be the core of this approach and this will be complemented by usual recommendations regarding dietary P restriction. Dietitians will be available to provide counseling with regards to any aspect of the end-stage renal disease diet, as per usual dialysis unit practice<br>* Other names: Calcium carbonate;|
| Active Comparator: Liberalized phosphate control<br>Individuals in this arm will be exposed to a treatment strategy that allows P to rise above 2.00 mmol/L. This will be accomplished through structured reduction of P binders already in use (as per the algorithm detailed below). Rescue P binding will be instituted if P rises above 2.50 mmol/L. Dietitians will be available to provide counseling regarding any aspect of the end-stage renal disease diet, as per usual dialysis unit practice, but will not provide counseling on dietary P restriction unless the P rises above 2.50 mmol/L. | Drug: Calcium carbonate (Liberalized phosphate control)<br>* Individuals in this arm will be exposed to a treatment strategy that allows P to rise above 2.00 mmol/L. This will be accomplished through structured reduction of P binders already in use (as per the algorithm detailed below). Rescue P binding will be instituted if P rises above 2.50 mmol/L. Dietitians will be available to provide counseling regarding any aspect of the end-stage renal disease diet, as per usual dialysis unit practice, but will not provide counseling on dietary P restriction unless the P rises above 2.50 mmol/L.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum phosphate concentration |  | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who successfully achieved target serum P at week 26 based on the arm to which they were randomized |  | 26 weeks | 
| Treatment compliance as defined by taking the study medication at least 80% of the time |  | 26 weeks | 
| Number of serious adverse events |  | 26 weeks | 
| Number of hospitalizations for vascular reasons that are unrelated to dialysis access |  | 26 weeks | 
| Proportion of patients with a vascular death or non-fatal vascular event |  | 26 weeks | 
| Proportion of patients developing serum calcium > 2.60 mmol/L |  | 26 weeks | 
| Number of fractures |  | 26 weeks | 
| Number of patients developing calcific uremic arteriolopathy (ie, calciphylaxis) |  | 26 weeks | 
| Change in quality-of-life |  | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemodialysis, end-stage renal disease, mineral metabolism, serum phosphate, phosphate binders