Phosphate Level Management for Kidney Failure

(PHOSPHATE Trial)

Recruiting at 104 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

Trial Summary

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. ^{1 2 3 4 5}

Are 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. ^{1 6 7 8 9}

How 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. ^{1 2 5 7 10}

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.

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

Eligibility 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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Advances in pharmacotherapy for hyperphosphatemia in renal disease. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Phosphate Binders and Targets Over Decades: Do We have it Right Now? [2018]

4. Canada pubmed.ncbi.nlm.nih.gov

Phosphate binders: new products and challenges. [2018]

5. United States 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. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Oral phosphate binders. [2016]

7. Germany pubmed.ncbi.nlm.nih.gov

Oral phosphate binders in CKD - is calcium the (only) answer? [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Past, Present, and Future of Phosphate Management. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

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