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

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

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.

Study Overview

• Status: Completed
• Conditions: End-stage Renal Disease
• Intervention / Treatment: Drug: Calcium carbonate ( Intensive phosphate control); Drug: Calcium carbonate (Liberalized phosphate control)

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Capital District Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare
    • London, Ontario, Canada, N6G 2V4
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 yrs
2. Receiving chronic hemodialysis for > 90 days,
3. Dialysis prescription is currently no more than 4 sessions per week and prescribed as 3-5 hrs per session
4. Most recent P value 1.30-2.50 mmol/L
5. Receipt of a calcium-based P binder

Exclusion Criteria:

1. Patient is booked (with a known surgical date) for a live donor kidney transplant in the next 26 weeks
2. Planned switch to a dialysis schedule that involves > 16 hours per week of therapy within the next 26 weeks.
3. Planned switch to peritoneal dialysis within the next 26 weeks
4. Pregnancy
5. Albumin-corrected serum calcium > 2.60 mmol/L in the past year requiring reduction of the calcium carbonate dose
6. History of calciphylaxis
7. 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
8. Attending nephrologist believes an otherwise eligible patient is not a candidate for escalation of the current calcium dose
9. Co-enrollment in a clinical trial where the intervention is deemed to interfere with the adherence, safety or efficacy of the intervention provided herein

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive phosphate control; 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); 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; Other Names: Calcium carbonate
Active Comparator: Liberalized phosphate control; 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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum phosphate concentration	26 weeks

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Ron Wald, MDCM, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: November 20, 2013
• First Submitted That Met QC Criteria: November 25, 2013
• First Posted (Estimate): November 26, 2013

Study Record Updates

• Last Update Posted (Estimate): June 23, 2015
• Last Update Submitted That Met QC Criteria: June 22, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: end-stage renal disease; hemodialysis; mineral metabolism; serum phosphate; phosphate binders
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antacids; Calcium; Calcium, Dietary; Calcium Carbonate
• Other Study ID Numbers: 001 (NavyGHB)