Phosphate Level Management for Kidney Failure
(PHOSPHATE Trial)
Recruiting in Palo Alto (17 mi)
+104 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: The University of Queensland
Must be taking: Phosphate-lowering
Disqualifiers: Kidney transplant, Major illness, others
No Placebo Group
Trial Summary
What is the purpose of this trial?During end-stage kidney disease, clinical guidelines suggest reducing elevated phosphate levels in the blood. However, the effect of lowering blood phosphate levels on important patient-centred outcomes has never been tested. This trial will evaluate whether compared to high levels, lowering blood phosphate levels would reduce death or major events due to heart disease, improve physical health, and be cost-effective.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you must be on at least one phosphate-lowering medication to participate.
What data supports the effectiveness of phosphate-lowering medications for managing phosphate levels in kidney failure?
Research shows that non-calcium-based phosphate binders can effectively control high phosphate levels in kidney disease patients, reducing the risk of heart-related issues and death compared to calcium-based binders.
12345Are phosphate binders safe for managing phosphate levels in kidney failure?
Phosphate binders are generally considered safe for managing phosphate levels in kidney failure, but they can have side effects, especially affecting the stomach and intestines. Some types, like calcium-based binders, may lead to high calcium levels and other complications, while others like sevelamer and lanthanum carbonate have fewer side effects but can be expensive.
16789How does the Intensive and Liberal phosphate target treatment for kidney failure differ from other treatments?
This treatment is unique because it involves setting specific phosphate level targets (intensive or liberal) to manage kidney failure, using phosphate binders that do not contain calcium, which reduces the risk of vascular calcification and mortality compared to traditional calcium-based binders.
125710Eligibility Criteria
This trial is for adults with end-stage kidney disease (ESKD) who have been on dialysis for at least 3 months and are taking medication to lower phosphate levels. It's open to those over 45, or over 18 with diabetes, who can consent. People expecting a kidney transplant soon, in other trials affecting phosphate levels, or with illnesses likely causing death within six months cannot join.Inclusion Criteria
I have been on dialysis for kidney failure for at least 3 months.
I am currently taking medication to lower my phosphate levels.
Able to provide informed consent
+1 more
Exclusion Criteria
You have a serious illness that could cause death within the next 6 months, according to your doctor.
You are involved in a study that may change the level of phosphate in your blood.
I am scheduled for a kidney transplant.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants are randomized to either intensive or liberal serum phosphate targets and receive phosphate binders as per the assigned target
5 years
Follow-up
Participants are monitored for safety and effectiveness after treatment, focusing on cardiovascular events and quality of life
5 years
Participant Groups
The PHOSPHATE trial is testing whether it's better for patients' health and more cost-effective to aim for high or intensive targets in lowering blood phosphate levels among those with chronic kidney failure. The impact on survival rates, heart events, and physical well-being will be compared.
2Treatment groups
Experimental Treatment
Active Control
Group I: Intensive phosphate targetExperimental Treatment1 Intervention
Intensive serum phosphate target of ≤1.50 mmol/L.
Group II: Liberal phosphate targetActive Control1 Intervention
Liberal serum phosphate target of 2.0 to 2.5 mmol/L.
Intensive phosphate target is already approved in European Union, United States, Canada, Australia for the following indications:
🇪🇺 Approved in European Union as Phosphate binders for:
- Chronic kidney disease
- End-stage kidney disease
- Hyperphosphatemia
🇺🇸 Approved in United States as Phosphate binders for:
- Chronic kidney disease
- End-stage kidney disease
- Hyperphosphatemia
🇨🇦 Approved in Canada as Phosphate binders for:
- Chronic kidney disease
- End-stage kidney disease
- Hyperphosphatemia
🇦🇺 Approved in Australia as Phosphate binders for:
- Chronic kidney disease
- End-stage kidney disease
- Hyperphosphatemia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Red Deer Hospital;Red Deer, Canada
Humber River HospitalToronto, Canada
Michael Garron HospitalToronto, Canada
Trillium Health PartnersToronto, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
The University of QueenslandLead Sponsor
National Health and Medical Research Council, AustraliaCollaborator
Applied Health Research CentreCollaborator
Cambridge University Hospitals NHS Foundation TrustCollaborator
University of OtagoCollaborator
References
State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective. [2023]Phosphate binders are among the most common medications prescribed to patients with kidney failure receiving dialysis and are often used in advanced chronic kidney disease (CKD). In patients with CKD glomerular filtration rate category 3a (G3a) or worse, including those with kidney failure who are receiving dialysis, clinical practice guidelines suggest "lowering elevated phosphate levels towards the normal range" with possible strategies including dietary phosphate restriction or use of binders. Additionally, guidelines suggest restricting the use of oral elemental calcium often contained in phosphate binders. Nutrition guidelines in CKD suggest
Advances in pharmacotherapy for hyperphosphatemia in renal disease. [2018]Hyperphosphatemia in chronic kidney disease (CKD) is considered as an independent risk factor for surrogate clinical end points like vascular calcification (VC) and bone disease, or hard clinical outcomes like cardiovascular events. Various treatment options are available for phosphate removal or reduction. Calcium-based phosphate binders (CBB) with their possible positive calcium balance became culprits for progressive VC and increased mortality risk. Non-calcium-based binders (NCBB) treatment allowed a comparable control of hyperphosphatemia with a lower risk of hypercalcemia and a slower progression of VC. Recent data have shown a 22% risk reduction in all-cause mortality with NCBB compared to CBB treatment. The appropriate timing of phosphate binder initiation in CKD patients is still unclear. Recent reports in patients with CKD stages 3b-4 showed increased VC progression when actively treated compared to placebo and a positive calcium, but no negative phosphate balance.
Phosphate Binders and Targets Over Decades: Do We have it Right Now? [2018]In advanced renal disease, the kidney is unable to maintain phosphate balance due to decreased urinary excretion as well as the imbalance of the bone metabolic axis. It is well established that hyperphosphatemia is associated with increased cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, there are no randomized controlled trials that demonstrate a clear benefit on hard outcomes in lowering serum phosphate levels to recommended targets in the CKD or dialysis population. In addition, while calcium-based phosphate binders have traditionally been the standard of care in the treatment of hyperphosphatemia, data regarding the increased risk of vascular mineralization continues to emerge. Clinicians continue to search for new phosphate-lowering therapies as well as investigate novel nutritional perspectives. The Kidney Disease: Improving Global Outcomes is currently revising the guidelines on phosphate goals in CKD. This review will outline the history of phosphate targets and phosphate binders, and explore innovative phosphate-lowering therapies. Based on current data, clinicians moving forward should continue to treat end-stage renal disease patients with hyperphosphatemia based on individual risk factors for vascular mineralization.
Phosphate binders: new products and challenges. [2018]Optimal phosphate control in dialysis patients is extremely challenging. A growing awareness of the deleterious effect of mineral metabolism imbalances together with the lack of a satisfactory explanation for the exaggerated mortality rate in patients undergoing renal replacement therapy has led to a renewed effort to refine our approach to hyperphosphatemia. However, despite the remarkable improvements in dialysis techniques, phosphate control has not substantially improved. Achieving normo-phosphatemia presents a multitude of practical and scientific challenges related to the optimal target level, cardiovascular health, and drug toxicities. It is the aim of the present review to summarize briefly the controversies associated with currently available phosphate binders, a cornerstone in the current management of hyperphosphatemia.
A Study to Inform the Design of a National Multicentre Randomised Controlled Trial to Evaluate If Reducing Serum Phosphate to Normal Levels Improves Clinical Outcomes including Mortality, Cardiovascular Events, Bone Pain, or Fracture in Patients on Dialysis. [2020]Background. Retrospective, observational studies link high phosphate with mortality in dialysis patients. This generates research hypotheses but does not establish "cause-and-effect." A large randomised controlled trial (RCT) of about 3000 patients randomised 50 : 50 to lower or higher phosphate ranges is required to answer the key question: does reducing phosphate levels improve clinical outcomes? Whether such a trial is technically possible is unknown; therefore, a study is necessary to inform the design and conduct of a future, definitive trial. Methodology. Dual centre prospective parallel group study: 100 dialysis patients randomized to lower (phosphate target 0.8 to 1.4 mmol/L) or higher range group (1.8 to 2.4 mmol/L). Non-calcium-containing phosphate binders and questionnaires will be used to achieve target phosphate.
Oral phosphate binders. [2016]Hyperphosphatemia is an inevitable consequence of end-stage chronic kidney disease and is present in the majority of dialysis patients. Hyperphosphatemia is observationally and statistically associated with increased cardiovascular mortality among dialysis patients. Dietary restriction of phosphate and current dialysis modalities are not sufficiently effective to maintain serum phosphate levels within the recommended range, so the majority of dialysis patients require oral phosphate binders. However, the benefits of achieving the recommended range have yet to be shown prospectively. Unfortunately, conventional phosphate binders are not reliably effective and are associated with a range of limitations and side effects. Aluminum-containing agents are highly efficient but no longer widely used because of proven toxicity. Calcium-based salts are inexpensive, effective, and most widely used, but there is now concern about their association with hypercalcemia and vascular calcification. Sevelamer hydrochloride is associated with fewer adverse effects, but a large pill burden and high cost are limiting factors to its wider use. Lanthanum carbonate is another non-aluminum, calcium-free phosphate binder. Preclinical and clinical studies have shown a good safety profile, and it appears to be well tolerated and effective in reducing phosphate levels in dialysis patients; however, it is similarly expensive. Data on its safety profile over 6 years of treatment are now published. Achievement of opinion-based guidelines appears to have become an end in itself. Dialysis patient outcomes are worse than outcomes for many types of cancer, yet prospective, outcome-based randomized controlled trials are not being undertaken for reasons that are difficult to explain.
Oral phosphate binders in CKD - is calcium the (only) answer? [2022]All-cause mortality and cardiovascular- related mortality have both been linked to abnormal serum phosphate concentrations in chronic kidney disease (CKD). Aberrant serum phosphate concentration in patients with CKD has also been associated with adverse cardiac and renal outcomes. Early prevention or management of rising or high serum phosphate concentrations in patients with CKD is now considered to be an important intervention to prevent downstream complications resulting from the poor management of serum calcium and parathyroid hormone (PTH). It is widely considered that starting phosphate binder therapy early, with concurrent dietary management of serum phosphate, constitutes an effective course of interventions, although normalization of serum phosphate in dialysis patients remains atypical, unless specific dialytic measures are also undertaken. Calcium- based phosphate binders are often the first type of binders prescribed due to their low cost. Evidence shows that most phosphate binders are roughly equally effective in lowering serum phosphate concentrations in adults compared to placebo, with a small probability that sevelamer hydrochloride is better than calcium acetate or lanthanum carbonate. However, not all binders are created equal in regards to their safety profiles. The potential for accumulations and toxicities does exist with very long-term continuous exposure. We discuss these issues in the course of this review.
Past, Present, and Future of Phosphate Management. [2022]Cardiovascular (CV) disease (CVD) accounts for >50% of deaths with known causes in patients on dialysis. Elevated serum phosphorus levels are an important nontraditional risk factor for bone mineral disease and CVD in patients with chronic kidney disease (CKD). Given that phosphorus concentrations drive other disorders associated with increased CV risk (e.g., endothelial dysfunction, vascular calcification, fibroblast growth factor-23, parathyroid hormone), phosphate is a logical target to improve CV health. Phosphate binders are the only pharmacologic treatment approved for hyperphosphatemia. Although their safety has improved since inception, the mechanism of action leads to characteristics that make ingestion difficult and unpleasant; large pill size, objectionable taste, and multiple pills required for each meal and snack make phosphate binders a burden. Side effects, especially those affecting the gastrointestinal (GI) system, are common with binders, often leading to treatment discontinuation. The presence of "hidden" phosphates in processed foods and certain medications makes phosphate management even more challenging. Owing to these significant issues, most patients on dialysis are not consistently achieving and maintaining target phosphorus concentrations of
[New Developments in CKD-MBD. New aspects in phosphate binders]. [2021]In patients with end-stage renal disease (ESRD) , hyperphosphatemia contributes to secondary hyperparathyroidism and can lead to skeletal complications including fracture, and vascular calcification. Currently employed phosphate binders include calcium carbonate, sevelamer hydrochloride, and lanthanum carbonate. While these agents are effective at binding orally ingested phosphates, they vary in safety, potency, and off-target effects, some of which may be salutary (e.g., low-density lipoprotein and uric acid lowering with sevelamer) and others adverse (low turnover bone disease and progressive vascular calcification with calcium) . There remains a large unmet need for safe and effective phosphate binders with favorable off-target effects.
A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. [2019]A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. Over the past 30 years it has become apparent that hyperphosphatemia plays a major causative role across the entire spectrum of morbidity associated with advancing kidney dysfunction and failure. A large fraction (60% to 70%) of dietary phosphorus is absorbed and normally excreted by the kidneys. Ideally, as kidney function deteriorates, the net quantity of phosphorus absorbed from the GI tract should be proportionally reduced to match the decrease in kidney function. After initiation of chronic dialysis therapy, the absorbed phosphorus load should match the amount of phosphorus removed via dialysis plus any excreted by residual kidney function. Because it is very difficult to reduce dietary phosphorus to these levels, a variety of oral phosphorus binders have been employed. Currently available binders include alkaline aluminum, magnesium, and calcium salts (primarily calcium carbonate and calcium acetate), various iron salts, and the binding resin sevelamer hydrochloride. Lanthanum carbonate is the newest agent and will probably be released shortly. This review compares the theoretic and in vitro chemistry of these drugs with in vivo data obtained in both normal patients, and in patients with kidney failure. The clinical potency and potential toxicity of the binding agents are compared, and optimal drug administration strategies are also reviewed.