Phosphate Level Management for Kidney Failure

(PHOSPHATE Trial)

Recruiting at 119 trial locations

Overseen By Rona Smith

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Queensland

Must be taking: Phosphate-lowering

Disqualifiers: Kidney transplant, Major illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

3600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to manage phosphate levels in people with end-stage kidney disease on dialysis. Researchers aim to determine if maintaining lower phosphate levels can reduce risks such as heart problems and death, improve physical health, and be more cost-effective. Participants will join one of two groups: one with a liberal phosphate level and another with a more intensive, lower phosphate target. Those who have been on dialysis for at least three months and currently take phosphate-lowering medication might be suitable candidates. As an unphased trial, this study allows participants to contribute to important research that could enhance treatment strategies for others with similar conditions.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that controlling phosphate levels in people with kidney disease is crucial for their health. Studies indicate that phosphate binders can safely lower these levels. For instance, sevelamer, a type of phosphate binder, may reduce the risk of death in people undergoing dialysis.

Another study highlighted the long-term safety of a drug called tenapanor, which can simplify phosphate management by reducing the number of pills needed. While these findings are encouraging, they primarily focus on drugs that lower phosphate, not the specific targets being tested in this trial.

Overall, treatments for managing phosphate levels in kidney disease appear well-tolerated. Some safety information is available, but it mostly pertains to specific medications rather than targeting specific phosphate levels. Consulting a healthcare provider is always advisable to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores two different approaches to managing phosphate levels in kidney failure patients: an intensive phosphate target and a liberal phosphate target. Unlike standard treatments that might not differentiate between phosphate levels, this trial aims to determine the optimal phosphate range for patient health. By comparing these two strategies, researchers hope to discover which approach could potentially lead to better outcomes, such as fewer complications and improved overall health for individuals with kidney failure.

What evidence suggests that this trial's treatments could be effective for managing phosphate levels in kidney failure?

Research has shown that controlling phosphate levels is crucial for people with kidney failure, as high phosphate levels can cause health problems. This trial will compare two approaches: an Intensive phosphate target, aiming for a serum phosphate level of ≤1.50 mmol/L, and a Liberal phosphate target, aiming for a level of 2.0 to 2.5 mmol/L. Studies have found that phosphate binders can effectively lower phosphate levels in the blood. For instance, one study found that a treatment called tenapanor helped 69.2% of patients reach their target phosphate levels. Managing phosphorus is key to improving the health of those with kidney disease. Lowering phosphate levels may reduce heart disease complications and improve physical health. ^{2 3 6 7 8}

Who Is on the Research Team?

Ron Wald

Principal Investigator

St Michael's Hospital

Suetonia Green

Principal Investigator

University of Otago

Patrick Mark

Principal Investigator

University of Glasgow

Rathika Krishnasamy

Principal Investigator

The University of Queensland

Michael Walsh

Principal Investigator

Hamilton Centre for Kidney Research

Rona Smith

Principal Investigator

University of Cambridge

Sunil Badve

Principal Investigator

The University of Queensland

Are You a Good Fit for This Trial?

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Intensive phosphate target
• Liberal phosphate target

Trial Overview 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.

How Is the Trial Designed?

Group I: Intensive phosphate target Experimental Treatment 1 Intervention

Intensive serum phosphate target of ≤1.50 mmol/L.

Group II: Liberal phosphate target Active Control 1 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 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

Who Is Running the Clinical Trial?

The University of Queensland

Lead Sponsor

Trials

149

Recruited

71,700+

National Health and Medical Research Council, Australia

Collaborator

Trials

167

Recruited

473,000+

Applied Health Research Centre

Collaborator

Trials

23

Recruited

70,900+

Cambridge University Hospitals NHS Foundation Trust

Collaborator

Trials

280

Recruited

501,000+

University of Otago

Collaborator

Trials

40

Recruited

60,100+

Published Research Related to This Trial

Hyperphosphatemia is common in dialysis patients and is linked to higher cardiovascular mortality, highlighting the need for effective phosphate management.

Current phosphate binders, including lanthanum carbonate, show promise in reducing phosphate levels with a good safety profile, but issues like cost and the lack of prospective outcome-based trials limit their use and effectiveness in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral phosphate binders. Hutchison, AJ.[2016]

Abnormal serum phosphate levels in chronic kidney disease (CKD) patients are linked to higher risks of all-cause and cardiovascular mortality, making early management of phosphate levels crucial to prevent serious health complications.

While calcium-based phosphate binders are commonly prescribed due to their low cost and effectiveness in lowering serum phosphate, safety concerns arise from potential long-term toxicities, highlighting the need for careful monitoring and consideration of alternative binders like sevelamer hydrochloride.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral phosphate binders in CKD - is calcium the (only) answer? Goldsmith, D., Covic, A.[2022]

A prospective study involving 100 dialysis patients is being conducted to determine if targeting lower phosphate levels (0.8 to 1.4 mmol/L) compared to higher levels (1.8 to 2.4 mmol/L) can be achieved and maintained, which will help design a larger trial to assess the impact of phosphate on health outcomes.

The primary goal is to evaluate the success of achieving and maintaining phosphate levels, while secondary outcomes will include consent rates, dropout rates, and cardiovascular events, ultimately aiming to clarify the relationship between phosphate levels and mortality in dialysis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Bhargava, R., Kalra, PA., Brenchley, P., et al.[2020]

Elevated serum phosphorus levels are a significant risk factor for cardiovascular disease in patients with chronic kidney disease, making phosphate management crucial for improving cardiovascular health.

Current phosphate binders have limitations, including side effects and difficulty in adherence, leading to the need for new therapies like EOS789 and tenapanor, which target different intestinal phosphate absorption pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past, Present, and Future of Phosphate Management. Doshi, SM., Wish, JB.[2022]

Non-calcium-based phosphate binders (NCBB) are associated with a 22% reduction in all-cause mortality compared to calcium-based phosphate binders (CBB), making them a safer option for managing hyperphosphatemia in chronic kidney disease (CKD).

The timing of initiating phosphate binder treatment in CKD patients remains uncertain, as recent studies indicate that active treatment may lead to increased vascular calcification progression without effectively balancing phosphate levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in pharmacotherapy for hyperphosphatemia in renal disease. Spasovski, G.[2018]

Phosphate binders are commonly prescribed for patients with chronic kidney disease (CKD) and kidney failure, but there is no clear evidence that one class of binder is superior to another in improving clinical outcomes, despite their widespread use.

The use of phosphate binders can significantly increase the number of pills patients must take and their out-of-pocket costs, raising concerns about their overall benefit and the best options for managing phosphate levels in CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective. Scialla, JJ., Kendrick, J., Uribarri, J., et al.[2023]

Phosphorus binders are crucial for managing hyperphosphatemia in patients with chronic kidney failure, as they help reduce dietary phosphorus absorption when kidney function declines.

The review compares various binders, including calcium salts, iron salts, and the new lanthanum carbonate, assessing their effectiveness and potential toxicity, which is important for optimizing treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. Emmett, M.[2019]

In patients with end-stage renal disease, high phosphate levels can lead to serious complications like fractures and vascular calcification, highlighting the importance of effective phosphate binders.

Current phosphate binders, such as calcium carbonate and sevelamer, vary in their safety and effectiveness, with some having beneficial effects like lowering LDL cholesterol, while others may cause adverse effects like low turnover bone disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New Developments in CKD-MBD. New aspects in phosphate binders]. Yokoyama, K.[2021]

Hyperphosphatemia, or high phosphate levels, is linked to increased cardiovascular risks and mortality in patients with chronic kidney disease (CKD), but there are no randomized controlled trials proving that lowering phosphate levels improves hard outcomes in these patients.

Traditional calcium-based phosphate binders may pose a risk of vascular mineralization, prompting the need for new phosphate-lowering therapies and individualized treatment approaches based on patient risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphate Binders and Targets Over Decades: Do We have it Right Now? Marcuccilli, M., Chonchol, M., Jovanovich, A.[2018]

Phosphate control in dialysis patients remains a significant challenge, with no substantial improvements despite advancements in dialysis techniques, highlighting the complexity of managing hyperphosphatemia.

Current phosphate binders, which are essential for managing high phosphate levels, come with controversies regarding their effectiveness and potential toxicities, indicating a need for better treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphate binders: new products and challenges. Bellasi, A., Kooienga, L., Block, GA.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6513594/

Phosphate binders for preventing and treating chronic kidney ... Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD)

2. ajkd.org ajkd.org/article/S0272-6386(25)00937-0/fulltext

Tenapanor: An Update on Evidence of Effectiveness and ... The target range was achieved in 69.2% of patients. Thus, tenapanor is effective in reducing serum phosphate levels in kidney failure at doses< ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2590059522000449

The Impact of Phosphorus Management Today on Quality ... Patients with kidney failure and early stages of chronic kidney disease often develop hyperphosphatemia, which is associated with negative outcomes.

4. bmcnephrol.biomedcentral.com bmcnephrol.biomedcentral.com/articles/10.1186/s12882-021-02441-8

Implementation and effectiveness of an intensive education ... The intensive education program can effectively improve serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders among hemodialysis ...

5. kireports.org kireports.org/article/S2468-0249(22)01073-7/fulltext

Past, Present, and Future of Phosphate Management Although phosphate binders have been found to reduce phosphorus concentrations in clinical trials, many patients on dialysis are still unable to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03573089

NCT03573089 | Pragmatic Randomised Trial of High Or ... This trial will evaluate whether compared to high levels, lowering blood phosphate levels would reduce death or major events due to heart disease, improve ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2468024922010737

Review Past, Present, and Future of Phosphate Management This is supported by a Cochrane systematic review of phosphate binders, which found in patients on dialysis, sevelamer may lead to lower all-cause death ( ...

8. hhs.texas.gov hhs.texas.gov/sites/default/files/documents/jan-2024-durb-agenda-item5z.pdf

Phosphate Binders Review The safety and efficacy of sevelamer carbonate in lowering serum phosphorus levels were studied in patients ≥ 6 years of age with CKD. However, limited data ...