Incremental Hemodialysis: The TwoPlus Trial

Study Overview
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Brief Summary
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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.

Detailed Description
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This study will analyze the effects of differentiated care with individualized hemodialysis on patient health related quality of life, fatigue, employment, and caregiver burden in patients with Kidney dysfunction requiring dialysis (KDRD) and appreciable kidney function. This study will compare the outcomes in survival, hospitalization, preservation of the kidney function and quality of life between hemodialysis tailored to each patient needs (incremental) and conventional hemodialysis.

Official Title
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Comparative Effectiveness of an Individualized Model of Hemodialysis Versus Conventional Hemodialysis

Conditions
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End-Stage Kidney Disease

Intervention / Treatment
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* Device: Hemodialysis twice weekly
* Other: Hemodialysis thrice weekly


Participation Criteria
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Eligibility Criteria
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Patient eligibility Criteria: Inclusion Criteria: Clinical Inclusion Criteria: Age ≥ 18 years Incident kidney dysfunction requiring dialysis (KDRD) started on maintenance, in-center hemodialysis (HD), or anticipated to be started on maintenance, in-center HD within the next 6 weeks Has received ≤18 sessions of intermittent HD (i.e., on HD for ≤6 weeks) at the time patient is approached for potential study participation Residual Kidney Function Inclusion Criteria: Kidney urea clearance# ≥3.5 mL/min/1.73 m2 Urine volume# of ≥500 mL/24 h Exclusion Criteria: Pre-HD serum K ≥5.8 mEq/L, Na ≤125 mEq/L, or bicarbonate level ≤17 mEq/L Requirement or anticipated requirement of high-volume ultrafiltration Unable or unwilling to follow the study protocol for any reason Known pregnancy or planning to attempt to become pregnant or lactating women Estimated survival or dialysis modality change or center transfer <6 months Caregiver Eligibility Criteria: be at least 18 years old be the main caregiver (at patient's choice) be a close relative of the patient (spouse, child, sibling, parent, grandchild) have no known psychiatric and neurologic disorders (through direct inquiry from the person) not be a member of the medical or healthcare team not be the caregiver for another patient with chronic illness not have experienced severe life events within prior 3 months of enrollment (through direct inquiry from the person)

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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No

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
Interventional Model Description: This study is a randomized parallel-group type 1 hybrid study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clinically-matched Incremental Hemodialysis ( CMIHD)<br>Randomized group to have hemodialysis prescription tailored based on residual kidney function and clinical manifestations starting at twice weekly. | Device: Hemodialysis twice weekly<br>* Frequency and duration of hemodialysis is tailored to the patient. Adjuvant pharmacotherapy is prescribed to maintain volume, electrolyte and acid-base homeostasis ( e.g., diuretics, sodium bicarbonate and potassium binding patiromer)<br>|
| Active Comparator: Conventional Hemodialysis (CHD)<br>Randomized group to conventional three times a week hemodialysis. | Other: Hemodialysis thrice weekly<br>* Conventional hemodialysis regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Clinical events of safety | composite of all-cause Emergency Department visits, hospitalizations, or death | year 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EuroQOL-5D-5L scores Health-related quality of life Health-related quality of life and residual kidney function | Compare the effects of CMIHD and CHD - The descriptive system covers 5 dimensions of health (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with 5 levels of severity in each dimension (no problems, slight problems, moderate problems, severe problems, and unable to perform or extreme problems - Values are anchored at 1 (full health) and 0 (a state as bad as being dead) as required by their use in economic evaluation. Values less than 0 represent health states regarded as worse than a state that is as bad as being dead. | year 2 | 
| Trail Making Test B scores Health-related quality of life Health-related quality of life and residual kidney function | Patient participants' cognitive function will be assessed using change in Trail Making Test B score - The Trail Making Test measures your visual attention, mental flexibility, processing speed, and motor speed based on how quickly and accurately you connect dots in ascending order (either numerically or with alternating numbers and letters). The test can be used to diagnose dementia and other cognitive disorders - Higher scores indicate a higher degree of cognitive impairment | Baseline and months 6, 12, 18, & 24 | 
| Standardized Outcomes in Nephrology (SONG) scores Health-related quality of life Health-related quality of life and residual kidney function | SONG-HD Fatigue score - The SONG-HD Fatigue measure consists of three items that assess (1) the effect of fatigue on life participation, (2) tiredness, and (3) level of energy. These dimensions are assessed on a four-point Likert scale indicating increasing severity, ranging from zero (not at all) to three (severely). Higher scores meaning higher severity | Baseline and months 6, 12, 18, & 24 | 
| Time to recover from hemodialysis (HD) Health-related quality of life Health-related quality of life and residual kidney function | Patient-reported functional status and fatigue will be assessed using Time to recover from HD | Baseline and monthly up to 2 years | 
| Caregiver burden Zarit Caregiver Burden Scores Health-related quality of life Health-related quality of life and residual kidney function | Caregiver burden will be assessed using the Zarit Caregiver Burden Scale - The ZBI consists of 22 items rated on a 5-point Likert scale that ranges from 0 (never) to 4 (nearly always) with the sum of scores ranging between 0-88. 9. Higher scores indicate greater burden. A score of 17 or more was considered high burden. | Baseline, months 6, 12, 18, & 24 | 
| Change in urine output | Urine collections will be analyzed at the lab used by the dialysis center | Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2 | 
| Change in kidney urea clearance (mL/min/1.73 m2) | Urine collections will be analyzed at the lab used by the dialysis center | Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2 | 
| Change in kidney creatinine clearance (mL/min/1.73 m2) | Urine collections will be analyzed at the lab used by the dialysis center | Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2 | 
| Hospital free days per 100 patient-days | The duration of hospital-free days will be determined for each patient and calculated in the whole cohort per 100 patient-days. It is anticipated an array of hospitalization events for each participant, ranging from no hospitalization to frequent hospitalizations per study period. All periods of hospitalization, per each participant, will be analyzed. A period of hospitalization will be computed from date of hospital admission to the date of discharge. Hospital-free days may include one or more discrete time segments of non-hospitalization between periods hospitalization. The total hospital-free days per patient participant will be calculated as total study days - hospitalization days. Hospital-free days will be normalized per 100 patient-days. | year 2 | 
| Illness Intrusiveness Rating Scale | Patients will rate the degree of interference caused by HD treatments on the following domains: health, diet, work, active and passive recreation, financial situation, relationship with spouse, sex life, family and other social relations, self-expression/self- improvement, religious expression, and community/civic involvement. Individual item ratings and the sum across ratings will be recorded. The total scale has a range of 13 (minimum intrusiveness) to 91 (extreme intrusiveness). | Assessed at baseline and monthly up to 2 years | 
| Employment status | The employment status for patients and caregivers will be assessed through surveys. | Baseline and months 6, 12, 18 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Clinically-Matched Incremental Hemodialysis