Incremental Hemodialysis: The TwoPlus Trial

Official title

Comparative Effectiveness of an Individualized Model of Hemodialysis Versus Conventional Hemodialysis

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Number of Clinical events of safety [Time frame: year 2]

Secondary outcome measures (11)

• EuroQOL-5D-5L scores Health-related quality of life Health-related quality of life and residual kidney function [Time frame: year 2]
• Trail Making Test B scores Health-related quality of life Health-related quality of life and residual kidney function [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Baseline, months 6, 12, 18, & 24]
• Change in urine output [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: year 2]
• Illness Intrusiveness Rating Scale [Time frame: Assessed at baseline and monthly up to 2 years]
• Employment status [Time frame: Baseline and months 6, 12, 18 and 24]

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 12 weeks
• Has received ≤36 sessions of intermittent HD (i.e., on HD for ≤12 weeks) at the time patient is approached for potential study participation

Residual Kidney Function Inclusion Criteria:

• Kidney urea clearance ≥ 2.0 mL/min
• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• University of Florida — Jacksonville
• Emory University — Atlanta
• Johns Hopkins University School of Medicine (JHUSM) — Baltimore
• Massachusetts General Hospital — Boston
• University of Mississippi Medical Center — Jackson
• Renal Research Institute (RRI) — New York
• Northwell Health — Queens
• University of North Carolina Chapel Hill — Chapel Hill
• … and 2 more centers

Publications

• Gautam SC, Awad AS, Niyyar VD, Flythe JE, Abdel-Rahman EM, Raimann JG, Woldemichael JA, Sheikh HI, Gaurav R, Kotanko P, Yang X, Gencerliler N, Divers J, Murea M. Patient monitoring in a pragmatic, multicenter trial of incremental hemodialysis: early experience from the TwoPlus randomized controlled trial. BMC Nephrol. 2025 Dec 9;27(1):39. doi: 10.1186/s12882-025-04659-2. PMID 41366335
• Murea M, Foley KL, Gautam SC, Flythe JE, Raimann JG, Abdel-Rahman E, Awad AS, Niyyar VD, Kovach C, Roberts GV, Jefferson NM, Conway PT, Rosales LM, Woldemichael J, Sheikh HI, Raman G, Huml AM, Knicely DH, Hasan I, Makadia B, Lea J, Daugirdas JT, Gencerliler N, Divers J, Kotanko P; TwoPlus Research Consortium; Nwaozuru UC. Protocol for the process evaluation of a randomised clinical trial of increm PMID 41314824
• Murea M, Raimann JG, Divers J, Maute H, Kovach C, Abdel-Rahman EM, Awad AS, Flythe JE, Gautam SC, Niyyar VD, Roberts GV, Jefferson NM, Shahidul I, Nwaozuru U, Foley KL, Trembath EJ, Rosales ML, Fletcher AJ, Hiba SI, Huml A, Knicely DH, Hasan I, Makadia B, Gaurav R, Lea J, Conway PT, Daugirdas JT, Kotanko P; Two Plus Research Consortium. Comparative effectiveness of an individualized model of hemod PMID 38943204

Identifiers

NCT: NCT05828823 · IRB00092986 · CER-2022C1-26300

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗