A Pilot Trial of Twice-weekly Versus Thrice-weekly Hemodialysis in Patients With Incident End-stage Kidney Disease

Study Overview
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Brief Summary
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The optimal frequency of hemodialysis treatments in patients with incident end-stage kidney disease in not known. This pilot trial will randomize patients with incident end-stage kidney disease due to chronic kidney disease progression to two different regimens of hemodialysis: i) twice-weekly hemodialysis for six weeks with adjuvant pharmacologic medications followed by thrice-weekly hemodialysis, or ii) thrice-weekly hemodialysis. The study will test feasibility of stepwise hemodialysis, and the effects of the two regimens of hemodialysis on residual kidney function.

Official Title
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A Randomized Pilot Study of Hemodialysis Initiation Comparing Twice-Weekly Hemodialysis Plus Dialysis-Sparing Therapy Versus Thrice-Weekly Hemodialysis (The TWOPLUS-HD Trial)

Conditions
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End Stage Renal Failure on Dialysis

Intervention / Treatment
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* Other: Hemodialysis
* Drug: Patiromer Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Incident ESKD from CKD progression (including a failing renal transplant) Are deemed to require dialysis initiation by the treating nephrologist Have elected HD for renal replacement therapy (RRT) Exclusion Criteria: Have urine output <500ml per day Have ESKD as a result of severe acute kidney injury (AKI) (stage 3 AKI defined by Acute Kidney Injury Network [AKIN]) criteria) Abrupt decline in kidney function preceding HD therapy initiation (i.e., if eGFR was ≥30 mL/min/1.73 m2 3 months prior to the initiation of dialysis therapy) Are scheduled to undergo transplantation from a live donor within the next 6 months Have an active diagnosis of hepatorenal syndrome Have a significant malignancy that is likely to impact survival Have a medical condition that would jeopardize the safety of the subject.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemodialysis and Pharmacologic Therapy<br>Hemodialysis regimen at the initiation of dialysis treatment: Twice-weekly hemodialysis plus adjunctive pharmacologic therapy (loop diuretic, potassium-binding agent, and sodium bicarbonate) for six consecutive weeks, continued by thrice-weekly hemodialysis (intervention group) | Other: Hemodialysis<br>* Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.<br>Drug: Patiromer Oral Product<br>* Participants in the intervention group who develop hyperkalemia, during the first six weeks of receiving hemodialysis twice per week, will be treated with Patiromer.<br>|
| Active Comparator: Conventional Hemodialysis Regimen<br>Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis | Other: Hemodialysis<br>* Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' Adherence to Study Protocol | ≥95% of participants randomized in the intervention group will adhere to the HD regimen. All participants who completed 6 and 12 months of follow-up completed interdialytic timed urine collections - Patient adherence to the study protocol was assessed by the number of participants randomized to each intervention who adhered to the study protocol and at 6 months and at 12 months | 6 months, 12 months, 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour Urine Volume | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed at baseline, 6 Weeks, 12 Weeks and 24 Weeks | Baseline, 6 Weeks, 12 Weeks, 24 Weeks | 
| Change in Residual Kidney Function - Urea Clearance | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24. | Baseline, 6 Weeks, 12 Weeks, 24 Weeks | 
| Change in Residual Kidney Function - Creatinine Clearance | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24. | Baseline, 6 Weeks, 12 Weeks, 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Kidney Disease, Kidney Function