Peritoneal Ultrafiltration for Chronic Kidney Failure

(IPUF-HD Trial)

Overseen By Patricia Jarosz, MMASc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Disqualifiers: Uncontrolled diabetes, Active infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if an additional type of dialysis, called peritoneal ultrafiltration, can enhance sodium removal for individuals with chronic kidney failure. Regular hemodialysis often fails to eliminate sufficient sodium, which can impact health. Participants will undergo this extra dialysis twice a week for three weeks to assess its effectiveness in improving sodium removal and managing symptoms like high blood pressure. Ideal candidates for this trial include those who gain significant weight between dialysis sessions or struggle to reach their target weight with current treatment. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this method is safe for chronic kidney failure patients?

Research has shown that peritoneal ultrafiltration, a type of dialysis, can sometimes lead to complications. One major issue is ultrafiltration failure, where the procedure fails to effectively remove fluid. This problem is known in peritoneal dialysis. Additionally, some patients may experience a decrease in their body's ability to filter fluids over time, leading to technique failure, where the method stops working properly.

Another study found that some patients experienced serious health issues, including deaths, mostly related to other health problems like liver failure. These serious events were not solely caused by the dialysis method.

Overall, while peritoneal ultrafiltration has been effective for many, patients considering joining a clinical trial should be aware of the potential risks and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about interdialytic peritoneal ultrafiltration for chronic kidney failure because it offers a different approach compared to traditional dialysis. Unlike standard hemodialysis, which typically occurs several times a week at a clinic and uses a machine to filter blood, this new method uses a 10% dextrose solution to gently remove excess fluid from the body through the peritoneal cavity. This technique is less invasive and can be done more frequently, potentially leading to better fluid balance and improved quality of life for patients. Additionally, it may allow for more flexible treatment schedules, which could be a game-changer for many individuals managing their condition.

What evidence suggests that interdialytic peritoneal ultrafiltration is effective for chronic kidney failure?

Research has shown that peritoneal dialysis (PD) effectively removes extra salt from the body. Studies have found that PD helps manage fluid levels and reduces problems linked to chronic kidney disease. One study found that patients with kidney failure who used PD had better control of their salt levels, which is important for preventing high blood pressure. PD is also recognized as a reliable form of home dialysis with good long-term results. In this trial, participants will receive interdialytic peritoneal ultrafiltration, a form of PD, between hemodialysis sessions. This approach could improve salt removal and potentially lead to better health for patients with chronic kidney failure. ^{1 3 6 7 8}

Who Is on the Research Team?

Christopher W. McIntyre, MD, PhD

Principal Investigator

Lawson Research Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are on hemodialysis up to three times a week for chronic kidney failure but can't reach their prescribed dry weight. They should gain at least 4% of their dry weight between sessions and be able to consent. It's not for those with conditions that rule out peritoneal dialysis or MRI, uncontrolled diabetes, active infections, non-compliance with hemodialysis, or very low sodium levels.

Inclusion Criteria

I can't reach my target weight with my current treatment.

I undergo hemodialysis up to three times a week.

I need more dialysis sessions to reach my target weight.

Exclusion Criteria

I cannot undergo peritoneal dialysis due to health reasons.

I cannot have an MRI due to certain health reasons.

My diabetes is not well-controlled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Assessment of residual renal function, volume, hemodynamic and cardiac status during HD

1 week

Treatment

Participants receive interdialytic peritoneal ultrafiltration with a 10% dextrose solution, twice a week for three consecutive weeks

3 weeks

2 visits per week (in-center)

Wash-out

Monitoring of potential residual effects of the iPUF intervention

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Interdialytic Peritoneal UltraFiltration

Trial Overview

The study tests if extra peritoneal dialysis using a dextrose solution can better remove excess sodium from tissues in-between regular hemodialysis sessions. Ten patients will have this additional treatment twice weekly for three weeks and undergo leg MRIs to measure tissue sodium before and after the study.

How Is the Trial Designed?

Group I: Interdialytic peritoneal ultrafiltration Experimental Treatment 1 Intervention

Will receive incremental interdialytic peritoneal ultrafiltration with a 10% dextrose solution, twice a week for three consecutive weeks

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Sequana Medical N.V.

Industry Sponsor

Trials

16

Recruited

820+

Published Research Related to This Trial

In a study of 90 long-term peritoneal dialysis patients, 19 experienced ultrafiltration failure (UFF), with 8 showing early UFF linked to a higher prevalence of diabetes and a rapid decline in residual renal function during the third year.

Patients with early UFF required significantly higher concentrations of dialysate glucose to maintain adequate ultrafiltration, suggesting that glucose levels on both sides of the peritoneal membrane may contribute to UFF, although the exact mechanisms remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis. Selgas, R., Bajo, MA., Castro, MJ., et al.[2020]

Ultrafiltration failure in peritoneal dialysis, defined as not achieving at least 400 ml of net ultrafiltration during a 4-hour dwell with 4.25% dextrose, is a major reason for patients needing to switch to hemodialysis.

Understanding the four main causes of ultrafiltration failure—high peritoneal transport state, low osmotic conductance to glucose, low effective peritoneal surface area, and high total peritoneal fluid loss—can help in diagnosing and managing this condition effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrafiltration failure in peritoneal dialysis: a pathophysiologic approach. Teitelbaum, I.[2022]

In a study of 177 patients on automated peritoneal dialysis, those with daily ultrafiltration (UF) below 750 mL at baseline had increased mortality over 2 years, indicating that poor UF is a significant risk factor for survival.

The study found no clear differences in comorbidities or nutritional status between patients with low and adequate UF, suggesting that the link between poor UF and increased mortality may be due to factors like membrane function rather than just health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the link between poor ultrafiltration and increased mortality in anuric patients on automated peritoneal dialysis? Analysis of data from EAPOS. Davies, SJ., Brown, EA., Reigel, W., et al.[2020]

In a study of nine peritoneal dialysis patients with poor ultrafiltration, using two icodextrin exchanges per day led to an average body weight reduction of 2.9 kg in six patients, indicating potential efficacy in managing fluid retention.

The treatment appeared safe, with stable HbA1c levels in diabetic patients and a slight decrease in serum sodium, suggesting that further long-term studies are needed to evaluate the overall impact and safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two icodextrin exchanges per day in peritoneal dialysis patients with ultrafiltration failure: one center's experience and review of the literature. Dousdampanis, P., Trigka, K., Chu, M., et al.[2021]

A study of 1,203 patients undergoing peritoneal dialysis (PD) from 1990 to 2019 showed significant improvements in patient survival rates, with 5-year survival increasing from 64% in the 1990-1999 cohort to 93% in the 2010-2019 cohort.

The rate of peritonitis, a common complication in PD, decreased significantly over time, from 0.278 episodes per patient-year to 0.162, indicating enhanced treatment protocols and care quality in the PD center.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving outcomes of peritoneal dialysis: secular trends at a single large center over three decades. Kang, M., Kim, YL., Kang, E., et al.[2021]

Ultrafiltration failure is a growing concern in patients on peritoneal dialysis, leading to increased cardiovascular risks and often resulting in the discontinuation of this treatment method.

This review highlights various strategies for preventing and treating ultrafiltration failure, emphasizing the importance of ongoing research to improve clinical outcomes for the increasing number of patients requiring renal replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective measures against ultrafiltration failure in peritoneal dialysis patients. Aguirre, AR., Abensur, H.[2022]

In a study comparing uraemic rats to healthy controls over 6 weeks of peritoneal dialysis (PD) fluid exposure, uraemic rats showed significant increases in serum urea and creatinine levels, indicating renal failure, along with changes in peritoneal tissue such as new blood vessel formation and elevated angiogenic factors.

While both uraemia and PD fluid exposure caused harmful changes to the peritoneum, the study found that uraemia did not significantly worsen the effects of PD fluid, suggesting that the damage from PD fluid is substantial on its own.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunopathological changes in a uraemic rat model for peritoneal dialysis. Zareie, M., De Vriese, AS., Hekking, LH., et al.[2017]

In patients undergoing continuous ambulatory peritoneal dialysis (CAPD), the accumulation of advanced glycation end products (AGEs) in the peritoneum is linked to severe interstitial fibrosis and microvascular sclerosis, which can lead to ultra-filtration failure.

The study found that the extent of AGE accumulation correlates with the progression of fibrosis and sclerosis, indicating that targeting AGEs may be a potential strategy to improve peritoneal ultra-filtration capacity in CAPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration. Honda, K., Nitta, K., Horita, S., et al.[2019]

Extracorporeal ultrafiltration (UF) is effective for short-term management of patients with congestive heart failure (CHF) who have severe fluid overload, leading to significant improvements in symptoms and quality of life.

Peritoneal dialysis (PD) may be more suitable for long-term treatment of CHF, but further research is needed to determine if these therapies can improve survival rates in patients with refractory CHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of peritoneal dialysis in the management of treatment-resistant congestive heart failure: A European perspective. Khalifeh, N., Vychytil, A., Hörl, WH.[2019]

In a study of five infants with acute kidney injury, continuous flow peritoneal dialysis (CFPD) significantly improved ultrafiltration rates compared to conventional peritoneal dialysis, achieving a median ultrafiltration rate of 6.7 mg/kg/h versus 1.7 mg/kg/h (p=0.042).

CFPD also enhanced clearance rates for urea and creatinine, with clearances of 19 mL/min/1.73 m² and 41 mL/min/1.73 m² respectively, compared to 6.89 mL/min/1.73 m² and 7.46 mL/min/1.73 m² with conventional PD (both p=0.043).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous flow peritoneal dialysis (CFPD) improves ultrafiltration in children with acute kidney injury on conventional PD using a 4.25 % dextrose solution. Nourse, P., Sinclair, G., Gajjar, P., et al.[2018]

Peritoneal dialysis is an effective treatment for end-stage chronic kidney failure, utilizing the peritoneum's vascularization to remove waste from the body, but it can lead to complications such as catheter dysfunction and infections.

Early recognition and management of complications are crucial for patient safety, as they can significantly impact treatment success and may necessitate a switch to haemodialysis if not addressed promptly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complications after placement of peritoneal catheter]. Mirković, TD., Popov, M., Korica, M., et al.[2019]

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