Incremental Hemodialysis Frequency for Kidney Failure

Recruiting at 11 trial locations

Overseen By Denisse A Funes

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Pregnancy, High potassium, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

350 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is to prospectively compare clinical effectiveness between clinically- matched incremental hemodialysis and conventional hemodialysis in patients with incident kidney dysfunction requiring dialysis and residual kidney function. The study will enroll 350 patients on chronic hemodialysis and 140 caregivers of enrolled patients. Patients will be randomized in 1:1 ratio to either incremental start hemodialysis or conventional hemodialysis. Caregivers will be followed along with patients for an average period of 2 years post randomization.

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 study team or your doctor.

What data supports the effectiveness of incremental hemodialysis for kidney failure?

Research suggests that incremental hemodialysis, which starts with fewer sessions per week, may help preserve remaining kidney function and improve patient comfort compared to the standard thrice-weekly schedule. This approach is particularly beneficial for patients who still have some kidney function left when they begin dialysis. ^{1 2 3 4 5}

Is incremental hemodialysis safe for humans?

Incremental hemodialysis, which involves starting with fewer sessions per week and increasing as needed, is considered safe and less burdensome for patients with kidney failure. Studies suggest it may help preserve remaining kidney function and improve quality of life. ^{1 2 3 6 7}

What makes Incremental Hemodialysis unique compared to other treatments for kidney failure?

Incremental Hemodialysis is unique because it starts with less frequent sessions, such as once or twice a week, which can be easier on patients and help preserve remaining kidney function longer. This approach is more personalized and can be adjusted based on the patient's needs, unlike the standard thrice-weekly schedule. ^{1 2 3 6 8}

Research Team

Mariana Murea, MD

Principal Investigator

Wake Forest Health Sciences

Peter Kotanko

Principal Investigator

Renal Research Institute

Eligibility Criteria

Adults over 18 with new-onset kidney dysfunction requiring dialysis can join this trial. They should have started or be starting in-center hemodialysis soon, and not been on it for more than 6 weeks. Participants need some remaining kidney function and urine output. Those with certain blood chemistry imbalances, high fluid removal needs, a short life expectancy, or pregnancy are excluded.

Inclusion Criteria

I am on or will start dialysis soon due to kidney problems.

I have had 18 or fewer dialysis sessions over 6 weeks or less.

Your kidney function is not working very well.

Exclusion Criteria

You need or may need a lot of fluid removed from your blood.

Your blood test shows high potassium, low sodium, or low bicarbonate levels before the study.

I am unable to follow or unwilling to commit to the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either incremental hemodialysis or conventional hemodialysis

2 years

Regular visits as per hemodialysis schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Caregiver Follow-up

Caregivers are followed along with patients to assess caregiver burden and quality of life

2 years

Treatment Details

Interventions

• Conventional Hemodialysis
• Hemodialysis thrice weekly
• Hemodialysis twice weekly
• Incremental Hemodialysis

Trial Overview The TwoPlus Trial is comparing two schedules of hemodialysis for people with kidney failure: one group will receive treatments twice a week while the other will have them three times a week. The goal is to see which frequency is better when patients still have some kidney function left.

Participant Groups

Group I: Clinically-matched Incremental Hemodialysis ( CMIHD) Experimental Treatment 1 Intervention

Randomized group to have hemodialysis prescription tailored based on residual kidney function and clinical manifestations starting at twice weekly.

Group II: Conventional Hemodialysis (CHD) Active Control 1 Intervention

Randomized group to conventional three times a week hemodialysis.

Conventional Hemodialysis is already approved in United States, European Union for the following indications:

Approved in United States as Conventional Hemodialysis for:

• End-stage kidney disease
• Chronic kidney disease progressing to dialysis-dependent kidney disease

Approved in European Union as Conventional Hemodialysis for:

• End-stage kidney disease
• Chronic kidney disease progressing to dialysis-dependent kidney disease

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Findings from Research

Recent studies suggest that more frequent daily hemodialysis may improve intermediate patient outcomes such as blood pressure control, anemia, and quality of life, which could be linked to better survival rates in dialysis patients.

Despite promising findings, current studies are small and lack the power to definitively prove that daily hemodialysis reduces mortality and morbidity, and no randomized controlled trials have been reported yet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is more frequent hemodialysis beneficial and what is the evidence? Lindsay, RM., Nesrallah, G., Suri, R., et al.[2019]

A pilot study involving 51 patients assessed the feasibility and safety of incremental-start hemodialysis (HD), showing high adherence rates (96%) to the treatment schedule and successful enrollment in a randomized study.

Patients in the incremental HD group experienced less decline in urine volume and solute clearance compared to those receiving conventional thrice-weekly HD, suggesting potential benefits of this approach, although further research with larger trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study. Murea, M., Patel, A., Highland, BR., et al.[2023]

Incremental hemodialysis (iHD), which involves once or twice weekly dialysis, may be a beneficial alternative to the standard thrice weekly schedule for patients with end-stage chronic kidney disease, as it can ease the transition into dialysis and potentially preserve residual kidney function longer.

Despite the advantages of iHD, such as improved patient quality of life and reduced 'dialysis shock', there are currently no standardized guidelines for its implementation, leading to variability in practice across different healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ABCs of personalized incremental dialysis start, Le Mans style. Torreggiani, M., Fois, A., Samoreau, C., et al.[2023]

Conventional thrice weekly hemodialysis has not led to significant improvements in clinical outcomes for patients, indicating a need for alternative treatment approaches.

More intensive hemodialysis regimens, such as daily short dialysis and nocturnal prolonged dialysis, show potential for reducing morbidity and mortality, suggesting they may be more effective options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

More intensive hemodialysis. Kliger, AS.[2009]

Twice-weekly hemodialysis may be a safe and effective treatment option for patients with substantial residual kidney function (RKF), potentially preserving RKF and vascular access longer than the standard thrice-weekly regimen.

Proposed criteria for selecting patients for twice-weekly hemodialysis include having a urine output greater than 500 ml/day and favorable health conditions, suggesting that individualized treatment plans could enhance patient quality of life and warrant further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Is Known and Unknown About Twice-Weekly Hemodialysis. Obi, Y., Eriguchi, R., Ou, SM., et al.[2018]

A study involving 26 participants revealed that patients with kidney failure strongly prefer an incremental approach to hemodialysis (HD), which involves starting with less than three sessions per week, to minimize disruption to their daily lives.

The most important outcomes for patients were quality of life, residual kidney function, and mortality, indicating that patients prioritize their overall well-being and daily functioning over strict adherence to traditional HD schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Australian Workshops on Patients' Perspectives on Hemodialysis and Incremental Start. Hegerty, K., Jaure, A., Scholes-Robertson, N., et al.[2023]

Incremental haemodialysis initiation, which involves fewer sessions or shorter durations than standard treatment, does not increase the risk of mortality compared to the standard 4-hour thrice-weekly approach, based on a systematic review of 26 studies with a total of 101,476 participants.

The review suggests that incremental haemodialysis may lead to reduced hospitalization rates and lower treatment costs, although evidence on quality of life and other adverse events is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of incremental initiation of haemodialysis on mortality: a systematic review and meta-analysis. Caton, E., Sharma, S., Vilar, E., et al.[2023]

Increasing the frequency of hemodialysis from twice to thrice weekly in 569 patients led to better control of pre-dialysis systolic blood pressure, particularly in those with higher baseline blood pressure, showing a decrease of 12 mm Hg.

Patients with higher weekly interdialytic weight gain (IDWG) experienced a decrease in ultrafiltration volume, while those with lower IDWG saw an increase, indicating that treatment frequency adjustments can impact fluid management differently based on individual patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic and Laboratory Changes during Incremental Transition from Twice to Thrice-Weekly Hemodialysis. Hur, I., Wenziger, C., Obi, Y., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Is more frequent hemodialysis beneficial and what is the evidence? [2019]

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

Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

The ABCs of personalized incremental dialysis start, Le Mans style. [2023]

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

More intensive hemodialysis. [2009]

5. Switzerland pubmed.ncbi.nlm.nih.gov

What Is Known and Unknown About Twice-Weekly Hemodialysis. [2018]

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

Australian Workshops on Patients' Perspectives on Hemodialysis and Incremental Start. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Impact of incremental initiation of haemodialysis on mortality: a systematic review and meta-analysis. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Hemodynamic and Laboratory Changes during Incremental Transition from Twice to Thrice-Weekly Hemodialysis. [2021]