Incremental Hemodialysis: The TwoPlus Trial

End-Stage Kidney Disease Clinical Trial

Official title:

Comparative Effectiveness of an Individualized Model of Hemodialysis Versus Conventional Hemodialysis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05828823
• Other study ID #: IRB00092986
• Secondary ID: CER-2022C1-26300
• Status: Recruiting
• Phase: N/A
• Start date: February 26, 2024
• Est. completion date: March 2028

Study information

• Verified date: November 2023
• Source: Wake Forest University Health Sciences
• Contact: Denisse A Funes
• Phone: 336-716-8671
• Email: dfunes[@]wakehealth.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: March 2028
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• End-Stage Kidney Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Device:
• Hemodialysis twice weekly
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)

Other:
• Hemodialysis thrice weekly
Conventional hemodialysis regimen

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine (JHUSM)	Baltimore	Maryland
United States	University of North Carolina Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia (UVA)	Charlottesville	Virginia
United States	Cleveland Clinic, Case Western Reserve University (CWRU)	Cleveland	Ohio
United States	University of Florida	Jacksonville	Florida
United States	Renal Research Institute (RRI)	New York	New York
United States	Atrium Health Wake Forest Baptist	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	Patient-Centered Outcomes Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Characterize implementation processes using mixed methods - Intervention characteristics	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	2 years
Other	Characterize implementation processes using mixed methods - Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations	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	2 years
Other	Characterize implementation processes using mixed methods - External factors that mediate implementation	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	2 years
Other	Characterize implementation processes using mixed methods - Adoption	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	2 years
Other	Characterize implementation processes using mixed methods - Reach	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	2 years
Other	Characterize implementation processes using mixed methods - Fidelity, to assess adherence to serial timed urine collection and HD treatment schedule	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	2 years
Other	Characterize implementation processes using mixed methods - Sustainability, to assess barriers and facilitators to maintaining intervention	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	2 years
Primary	Number of Clinical events of safety	composite of all-cause Emergency Department visits, hospitalizations, or death	year 2
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Employment status	The employment status for patients and caregivers will be assessed through surveys.	Baseline and months 6, 12, 18 and 24