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End-Stage Kidney DiseaseNCT05828823

Incremental Hemodialysis: The TwoPlus Trial

A study testing Hemodialysis twice weekly and Hemodialysis thrice weekly in people with End-Stage Kidney Disease, run by Wake Forest University Health Sciences at 10 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
End-Stage Kidney Disease
What is being tested?
Hemodialysis twice weekly and Hemodialysis thrice weekly
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
350 participants
Where
10 sitesUnited States
Study dates
26 Feb 2024to Jan 2031
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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:
Show all 13Show fewer
  • 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)

Trial locations and contacts

10 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Brenda Burciu contact

336-716-8671

Brindusa.Burciu@advocatehealth.org

Ben Bagwell contact

Benjamin.Bagwell@advocatehealth.org

10 sites in 1 country

United States10 sites, 10 recruiting

  • Emory University

    Atlanta, Georgia, 30322

    Vandana Dua Niyyar, vniyyar@emory.edu

    Vandana Dua Niyyar

    Recruiting

  • Johns Hopkins University School of Medicine (JHUSM)

    Baltimore, Maryland, 21218

    Gautam Samir, MD

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Sagar Nigwekar, 617-726-5050, SNIGWEKAR@mgh.harvard.edu

    Sagar Nigwekar

    Recruiting

  • University of North Carolina Chapel Hill

    Chapel Hill, North Carolina, 27599

    Jennifer Flythe, MD

    Recruiting

  • University of Virginia (UVA)

    Charlottesville, Virginia, 22904

    Emaad Abdel-Rahman, MD

    Recruiting

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

    Neville Dossabhoy, MD, 601-984-5670, ndossabhoy@umc.edu

    Neville Dossabhoy, MD

    Recruiting

  • University of Florida

    Jacksonville, Florida, 32209

    Alaa Awad, MD, Alaa.Awad@jax.ufl.edu

    Alaa Awad

    Recruiting

  • Renal Research Institute (RRI)

    New York, New York, 10065

    Rasha Hussein, MD, 212-331-1710, rasha.hussein@rriny.com

    Rasha Hussein, MD

    Recruiting

  • Northwell Health

    Queens, New York, 11427

    Steven Fishbane, 516-465-8200, Sfishbane@northwell.edu

    Steven Fishbane

    Recruiting

  • Atrium Health Wake Forest Baptist

    Winston-Salem, North Carolina, 27157

    Mariana Murea, MD

    Recruiting

Other trials in United States

About this study

Official title: Comparative Effectiveness of an Individualized Model of Hemodialysis Versus Conventional Hemodialysis

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.

Read the 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.

Being tested
Hemodialysis twice weekly, Hemodialysis thrice weekly
Keywords
Hemodialysis, Clinically-Matched Incremental Hemodialysis
Medical subject headings
Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hemodialysis twice weeklyDevice

    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)

  • Hemodialysis thrice weeklyOther

    Conventional hemodialysis regimen

Study groups in NCT05828823
Study groupRoleWhat they receive
Clinically-matched Incremental Hemodialysis ( CMIHD)ExperimentalRandomized group to have hemodialysis prescription tailored based on residual kidney function and clinical manifestations starting at twice weekly.
Receives: Device: Hemodialysis twice weekly
Conventional Hemodialysis (CHD)Active comparatorRandomized group to conventional three times a week hemodialysis.
Receives: Other: Hemodialysis thrice weekly

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Clinical events of safety

    composite of all-cause Emergency Department visits, hospitalizations, or death

    Measured: year 2

Secondary outcomes (11)

  1. 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.

    Measured: year 2

  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

    Measured: Baseline and months 6, 12, 18, & 24

  3. 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

    Measured: Baseline and months 6, 12, 18, & 24

  4. 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

    Measured: Baseline and monthly up to 2 years

  5. 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.

    Measured: Baseline, months 6, 12, 18, & 24

  6. Change in urine output

    Urine collections will be analyzed at the lab used by the dialysis center

    Measured: Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2

  7. Change in kidney urea clearance (mL/min/1.73 m2)

    Urine collections will be analyzed at the lab used by the dialysis center

    Measured: Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2

  8. Change in kidney creatinine clearance (mL/min/1.73 m2)

    Urine collections will be analyzed at the lab used by the dialysis center

    Measured: Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Year 2

  9. 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.

    Measured: year 2

  10. 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).

    Measured: Assessed at baseline and monthly up to 2 years

  11. Employment status

    The employment status for patients and caregivers will be assessed through surveys.

    Measured: Baseline and months 6, 12, 18 and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2023
  2. Study start26 Feb 2024
  3. Primary completionJul 2030 (estimated)
  4. Study completionJan 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This study is a randomized parallel-group type 1 hybrid study
Masking
None (open label)
Enrolment
350 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05828823
Sponsor's protocol ID
IRB00092986
Other IDs
CER-2022C1-26300
Status last verified
May 2026
First submitted
29 Mar 2023
Last updated
6 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
Yes: Available upon investigator request

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.

    PubMed 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 incremental-start versus conventional haemodialysis: the TwoPlus study. BMJ Open. 2025 Nov 28;15(11):e094392. doi: 10.1136/bmjopen-2024-094392.

    PubMed 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 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.

    PubMed 38943204

Questions about this trial

What is this clinical trial studying?

A study testing Hemodialysis twice weekly and Hemodialysis thrice weekly in people with End-Stage Kidney Disease, run by Wake Forest University Health Sciences at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Brenda Burciu (336-716-8671, Brindusa.Burciu@advocatehealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Clinical events of safety (time frame: year 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05828823, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026; AzTrials last refreshed its copy on 2 Nov 2026.

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