Back to resultsIncremental Hemodialysis: The TwoPlus Trial
Primary Purpose
End-Stage Kidney Disease
Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Hemodialysis twice weekly
Hemodialysis thrice weekly
Sponsored by
About this trial
This is an interventional treatment trial for End-Stage Kidney Disease focused on measuring Hemodialysis, Clinically-Matched Incremental Hemodialysis
Eligibility Criteria
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)
Sites / Locations
- UCLA
- Harbor University of California Los Angeles
- University of Florida
- Emory University
- Johns Hopkins University School of Medicine (JHUSM)
- Renal Research Institute (RRI)
- University of North Carolina Chapel Hill
- Atrium Health Wake Forest Baptist
- Cleveland Clinic, Case Western Reserve University (CWRU)
- University of Virginia (UVA)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Clinically-matched Incremental Hemodialysis ( CMIHD)
Conventional Hemodialysis (CHD)
Arm Description
Randomized group to have hemodialysis prescription tailored based on residual kidney function and clinical manifestations starting at twice weekly.
Randomized group to conventional three times a week hemodialysis.
Outcomes
Primary Outcome Measures
Number of Clinical events of safety
composite of all-cause Emergency Department visits, hospitalizations, or death
Secondary Outcome Measures
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.
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
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
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
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.
Change in urine output
Urine collections will be analyzed at the lab used by the dialysis center
Change in kidney urea clearance (mL/min/1.73 m2)
Urine collections will be analyzed at the lab used by the dialysis center
Change in kidney creatinine clearance (mL/min/1.73 m2)
Urine collections will be analyzed at the lab used by the dialysis center
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.
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).
Employment status
The employment status for patients and caregivers will be assessed through surveys.
Full Information
NCT ID
NCT05828823
First Posted
March 29, 2023
Last Updated
October 5, 2023
Sponsor
Wake Forest University Health Sciences
Collaborators
Patient-Centered Outcomes Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT05828823
Brief Title
Incremental Hemodialysis: The TwoPlus Trial
Official Title
Comparative Effectiveness of an Individualized Model of Hemodialysis Versus Conventional Hemodialysis
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2024 (Anticipated)
Primary Completion Date
September 2027 (Anticipated)
Study Completion Date
March 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
Patient-Centered Outcomes Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-Stage Kidney Disease
Keywords
Hemodialysis, Clinically-Matched Incremental Hemodialysis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This study is a randomized parallel-group type 1 hybrid study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
350 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Clinically-matched Incremental Hemodialysis ( CMIHD)
Arm Type
Experimental
Arm Description
Randomized group to have hemodialysis prescription tailored based on residual kidney function and clinical manifestations starting at twice weekly.
Arm Title
Conventional Hemodialysis (CHD)
Arm Type
Active Comparator
Arm Description
Randomized group to conventional three times a week hemodialysis.
Intervention Type
Device
Intervention Name(s)
Hemodialysis twice weekly
Intervention Description
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)
Intervention Type
Other
Intervention Name(s)
Hemodialysis thrice weekly
Intervention Description
Conventional hemodialysis regimen
Primary Outcome Measure Information:
Title
Number of Clinical events of safety
Description
composite of all-cause Emergency Department visits, hospitalizations, or death
Time Frame
year 2
Secondary Outcome Measure Information:
Title
EuroQOL-5D-5L scores Health-related quality of life Health-related quality of life and residual kidney function
Description
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.
Time Frame
year 2
Title
Trail Making Test B scores Health-related quality of life Health-related quality of life and residual kidney function
Description
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
Time Frame
Baseline and months 6, 12, 18, & 24
Title
Standardized Outcomes in Nephrology (SONG) scores Health-related quality of life Health-related quality of life and residual kidney function
Description
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
Time Frame
Baseline and months 6, 12, 18, & 24
Title
Time to recover from hemodialysis (HD) Health-related quality of life Health-related quality of life and residual kidney function
Description
Patient-reported functional status and fatigue will be assessed using Time to recover from HD
Time Frame
Baseline and monthly up to 2 years
Title
Caregiver burden Zarit Caregiver Burden Scores Health-related quality of life Health-related quality of life and residual kidney function
Description
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.
Time Frame
Baseline, months 6, 12, 18, & 24
Title
Change in urine output
Description
Urine collections will be analyzed at the lab used by the dialysis center
Time Frame
Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2
Title
Change in kidney urea clearance (mL/min/1.73 m2)
Description
Urine collections will be analyzed at the lab used by the dialysis center
Time Frame
Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2
Title
Change in kidney creatinine clearance (mL/min/1.73 m2)
Description
Urine collections will be analyzed at the lab used by the dialysis center
Time Frame
Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2
Title
Hospital free days per 100 patient-days
Description
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.
Time Frame
year 2
Title
Illness Intrusiveness Rating Scale
Description
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).
Time Frame
Assessed at baseline and monthly up to 2 years
Title
Employment status
Description
The employment status for patients and caregivers will be assessed through surveys.
Time Frame
Baseline and months 6, 12, 18 and 24
Other Pre-specified Outcome Measures:
Title
Characterize implementation processes using mixed methods - Intervention characteristics
Description
Process evaluation will include a) Intervention characteristics, to assess organizational readiness to change, intervention acceptability and appropriateness; b) Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations; c) External factors that mediate implementation; d) Adoption; e) Reach; f) Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and g) Sustainability, to assess barriers and facilitators to maintaining intervention
Time Frame
2 years
Title
Characterize implementation processes using mixed methods - Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations
Description
Process evaluation will include a) Intervention characteristics, to assess organizational readiness to change, intervention acceptability and appropriateness; b) Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations; c) External factors that mediate implementation; d) Adoption; e) Reach; f) Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and g) Sustainability, to assess barriers and facilitators to maintaining intervention
Time Frame
2 years
Title
Characterize implementation processes using mixed methods - External factors that mediate implementation
Description
Process evaluation will include a) Intervention characteristics, to assess organizational readiness to change, intervention acceptability and appropriateness; b) Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations; c) External factors that mediate implementation; d) Adoption; e) Reach; f) Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and g) Sustainability, to assess barriers and facilitators to maintaining intervention
Time Frame
2 years
Title
Characterize implementation processes using mixed methods - Adoption
Description
Process evaluation will include a) Intervention characteristics, to assess organizational readiness to change, intervention acceptability and appropriateness; b) Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations; c) External factors that mediate implementation; d) Adoption; e) Reach; f) Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and g) Sustainability, to assess barriers and facilitators to maintaining intervention
Time Frame
2 years
Title
Characterize implementation processes using mixed methods - Reach
Description
Process evaluation will include a) Intervention characteristics, to assess organizational readiness to change, intervention acceptability and appropriateness; b) Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations; c) External factors that mediate implementation; d) Adoption; e) Reach; f) Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and g) Sustainability, to assess barriers and facilitators to maintaining intervention
Time Frame
2 years
Title
Characterize implementation processes using mixed methods - Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule
Description
Process evaluation will include a) Intervention characteristics, to assess organizational readiness to change, intervention acceptability and appropriateness; b) Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations; c) External factors that mediate implementation; d) Adoption; e) Reach; f) Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and g) Sustainability, to assess barriers and facilitators to maintaining intervention
Time Frame
2 years
Title
Characterize implementation processes using mixed methods - Sustainability, to assess barriers and facilitators to maintaining intervention
Description
Process evaluation will include a) Intervention characteristics, to assess organizational readiness to change, intervention acceptability and appropriateness; b) Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations; c) External factors that mediate implementation; d) Adoption; e) Reach; f) Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and g) Sustainability, to assess barriers and facilitators to maintaining intervention
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Denisse A Funes
Phone
336-716-8671
Email
dfunes@wakehealth.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Brindusa Burciu
Phone
3367168671
Email
bburciu@wakehealth.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mariana Murea, MD
Organizational Affiliation
Wake Forest Health Sciences
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Kotanko
Organizational Affiliation
Renal Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Connie Rhee
Email
crhee@mednet.ucla.edu
First Name & Middle Initial & Last Name & Degree
Lisa Le
Email
lle7@hs.uci.edu
First Name & Middle Initial & Last Name & Degree
Connie Rhee
Facility Name
Harbor University of California Los Angeles
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kaymar Kalantar-Zadeh, MD
Facility Name
University of Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alaa Awad, MD
Email
Alaa.Awad@jax.ufl.edu
First Name & Middle Initial & Last Name & Degree
Debra Martin
Email
Debra.Martin3@jax.ufl.edu
First Name & Middle Initial & Last Name & Degree
Alaa Awad
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vandana Dua Niyyar
Email
vniyyar@emory.edu
First Name & Middle Initial & Last Name & Degree
Zohreh Forghani
Email
zohreh.forghani@emory.edu
First Name & Middle Initial & Last Name & Degree
Vandana Dua Niyyar
Facility Name
Johns Hopkins University School of Medicine (JHUSM)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21218
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gautam Samir, MD
Facility Name
Renal Research Institute (RRI)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jochen Raimann, MD
Facility Name
University of North Carolina Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Flythe, MD
Facility Name
Atrium Health Wake Forest Baptist
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana Murea, MD
Facility Name
Cleveland Clinic, Case Western Reserve University (CWRU)
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cassandra Kovach, MD
Facility Name
University of Virginia (UVA)
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22904
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emaad Abdel-Rahman, MD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Available upon investigator request
Learn more about this trial
Incremental Hemodialysis: The TwoPlus Trial
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