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

NCT01994733 | Completed Phase 2

• 1 other identifier: 001
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 5

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.

Conditions

End-stage Renal Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Serum phosphate concentration

  26 weeks

Secondary Outcomes (9)

• 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

Study Arms (2)

Intensive phosphate control

EXPERIMENTAL

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)

Liberalized phosphate control

ACTIVE COMPARATOR

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)

Interventions

Calcium carbonate ( Intensive phosphate control) DRUG

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

Also known as: Calcium carbonate

Intensive phosphate control

Calcium carbonate (Liberalized phosphate control) DRUG

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.

Liberalized phosphate control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Unity Health Toronto: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (5)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Capital District Health Authority

Halifax, Nova Scotia, B3H 1V7, Canada

Location

St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

Location

London Health Sciences Centre

London, Ontario, N6G 2V4, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Calcium Carbonate

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals

Study Officials

• Ron Wald, MDCM

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician, Division of Nephrology; Scientist, Li Ka Shing Knowledge Institute of St. Michael's Hospital

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: November 26, 2013
• Study Start: January 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: June 23, 2015

Record last verified: 2015-06

Locations

CA (5)