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

• ClinicalTrials.gov Identifier: NCT01994733
• Recruitment Status: Completed
• First Posted: November 26, 2013
• Last Update Posted: June 23, 2015
• Sponsor: St. Michael's Hospital, Toronto
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): Ron Wald, St. Michael's Hospital, Toronto

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
End-stage Renal Disease	Drug: Calcium carbonate ( Intensive phosphate control); Drug: Calcium carbonate (Liberalized phosphate control)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Two phosphAte taRGets in End-stage Renal Disease Trial (TARGET): Intensive vs Liberalized Phosphate Control in Hemodialysis Recipients
• Study Start Date: January 2014
• Actual Primary Completion Date: April 2015
• Actual Study Completion Date: April 2015

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Serum phosphate concentration [ Time Frame: 26 weeks ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

Foothills Medical Centre

Calgary, Alberta, Canada, T2N 2T9

Canada, Nova Scotia

Capital District Health Authority

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

St. Joseph's Healthcare

Hamilton, Ontario, Canada, L8N 4A6

London Health Sciences Centre

London, Ontario, Canada, N6G 2V4

St. Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Sponsors and Collaborators

St. Michael's Hospital, Toronto

Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Ron Wald, MDCM; St. Michael's Hospital, Toronto

More Information

• Responsible Party: Ron Wald, Staff Physician, Division of Nephrology; Scientist, Li Ka Shing Knowledge Institute of St. Michael's Hospital, St. Michael's Hospital, Toronto
• ClinicalTrials.gov Identifier: NCT01994733
• Other Study ID Numbers: 001
• First Posted: November 26, 2013
• Last Update Posted: June 23, 2015
• Last Verified: June 2015

Keywords provided by Ron Wald, St. Michael's Hospital, Toronto:

end-stage renal disease; hemodialysis; mineral metabolism; serum phosphate; phosphate binders

Additional relevant MeSH terms:

Kidney Diseases; Kidney Failure, Chronic; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Calcium, Dietary; Calcium Carbonate; Calcium; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents; Antacids; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents