Incremental Hemodialysis: The TwoPlus Trial
Comparative Effectiveness of an Individualized Model of Hemodialysis Versus Conventional Hemodialysis
2 other identifiers
interventional
350
1 country
10
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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Feb 2024
Longer than P75 for not_applicable
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 29, 2023
CompletedFirst Posted
Study publicly available on registry
April 25, 2023
CompletedStudy Start
First participant enrolled
February 26, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2028
January 29, 2026
October 1, 2025
3.5 years
March 29, 2023
January 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Clinical events of safety
composite of all-cause Emergency Department visits, hospitalizations, or death
year 2
Secondary Outcomes (11)
EuroQOL-5D-5L scores Health-related quality of life Health-related quality of life and residual kidney function
year 2
Trail Making Test B scores Health-related quality of life Health-related quality of life and residual kidney function
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
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
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
Baseline, months 6, 12, 18, & 24
- +6 more secondary outcomes
Other Outcomes (7)
Characterize implementation processes using mixed methods - Intervention characteristics
2 years
Characterize implementation processes using mixed methods - Inner setting characteristics, to assess barriers and facilitators to the adoption of HD intervention at the partnering organizations
2 years
Characterize implementation processes using mixed methods - External factors that mediate implementation
2 years
- +4 more other outcomes
Study Arms (2)
Clinically-matched Incremental Hemodialysis ( CMIHD)
EXPERIMENTALRandomized group to have hemodialysis prescription tailored based on residual kidney function and clinical manifestations starting at twice weekly.
Conventional Hemodialysis (CHD)
ACTIVE COMPARATORRandomized group to conventional three times a week hemodialysis.
Interventions
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)
Eligibility Criteria
You may qualify if:
- 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
- Kidney urea clearance \<2.0 mL/min
- Urine volume# of ≥500 mL/24 h
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
University of Florida
Jacksonville, Florida, 32209, United States
Emory University
Atlanta, Georgia, 30322, United States
Johns Hopkins University School of Medicine (JHUSM)
Baltimore, Maryland, 21218, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Renal Research Institute (RRI)
New York, New York, 10065, United States
Northwell Health
Queens, New York, 11427, United States
University of North Carolina Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157, United States
University of Virginia (UVA)
Charlottesville, Virginia, 22904, United States
Related Publications (2)
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 incremental-start versus conventional haemodialysis: the TwoPlus study. BMJ Open. 2025 Nov 28;15(11):e094392. doi: 10.1136/bmjopen-2024-094392.
PMID: 41314824DERIVEDMurea 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 hemodialysis vs conventional hemodialysis: a study protocol for a multicenter randomized controlled trial (the TwoPlus trial). Trials. 2024 Jun 28;25(1):424. doi: 10.1186/s13063-024-08281-9.
PMID: 38943204DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mariana Murea, MD
Wake Forest Health Sciences
- PRINCIPAL INVESTIGATOR
Peter Kotanko
Renal Research Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 29, 2023
First Posted
April 25, 2023
Study Start
February 26, 2024
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
March 1, 2028
Last Updated
January 29, 2026
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
Available upon investigator request