Incremental Hemodialysis for Veterans in the First Year of Dialysis (IncHVets)

NCT ID: NCT05465044

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-01
• Study Completion Date: 2027-09-30

Brief Summary

In this pragmatic clinical trial, which will dovetail with Veterans' routine outpatient dialysis clinic visits in six VA medical centers, the investigators will study 252 Veterans with kidney disease who need to start dialysis treatment. If a Veteran is eligible for the study by making enough residual urine, he/she will have a 50% chance to be offered the usual three-times-per-week dialysis vs. twice-per-week dialysis that is gradually increased to three-times per- week over one year. The investigators will compare health-related quality of life, how long residual kidney function lasts, and other measures including safety in these two groups. By conducting this study, the investigators hope to understand 1) whether starting dialysis with less frequency is safe, effective, and can help Veterans and their care-partners to better cope with dialysis, and 2) if incremental dialysis can result in major cost benefits to the VA health care system, thus allowing more patients to stay in VA dialysis clinics vs. being transferred to outside clinics.

Detailed Description

Each year approx. 12,000 Veterans with worsening kidney disease develop end-stage renal disease (ESRD) and initiate dialysis treatment. They comprise >10% of the US incident ESRD population. Dialysis is costly and associated with impaired health-related quality of life (HRQOL) and high mortality risk, especially in the first dialysis treatment year. Currently, starting treatment with outright full-dose thrice-weekly hemodialysis (HD) from the outset of therapy is the standard of care regardless of patients' residual kidney function (RKF) and regardless of patients' and care-partners' suffering and preferences. Although not currently the standard of care, evidence suggests that gradual or incremental dialysis transition using an initial twice-weekly HD may confer substantial benefits including more dialysis-free time, longer RKF preservation, less trauma to patients' organs including their dialysis vascular access, lower frequency of intradialytic hypotensive events, less post-dialysis fatigue, and reduced patient suffering. Hence, incremental dialysis transition may result in improved HRQOL through better physical function, less fatigue, more energy, and better patient satisfaction and life participation by mitigating the burden of excessive dialysis in day-to-day life and on employment. Pragmatic studies with immediate impact are needed to shift the focus of dialysis from abrupt thrice-weekly HD start to a safe and effective personalized dialysis regimen.

In this multi-site, pragmatic, 1:1 randomized controlled trial (RCT), parallel with Veterans' routine dialysis therapy, the investigators will test the safety and efficacy of an incremental HD protocol, compared to standard-of-care thrice-weekly HD, in Veterans who meet the eligibility criteria. The investigators plan to compare twice-weekly (incremental) with thrice-weekly (conventional) HD initiation in 252 Veterans, who will transition to maintenance HD therapy in six VA centers. Assessing quarterly for up to 12 months, the investigators will study HRQOL physical health score as the primary endpoint, as well as dialysis symptom index and energy/fatigue score as secondary endpoints. Additional secondary outcome measures to collect and examine quarterly include preservation of the RKF, dialysis adequacy, nutritional status, and serum level of Growth Differentiation Factor 15. Safety assessments will include mortality, dialysis withdrawals, ER visits, hospitalizations, hyperkalemia, and major adverse cardiovascular events. In a substudy of 112 participating Veterans in three VA centers, the investigators will additionally examine cardiac measures including left ventricular mass, as well as mid-arm muscle circumference and physical performance.

This pragmatic RCT addresses a major unmet need in those Veterans who initiate dialysis by focusing on improving HRQOL and preserving RKF, the two strongest predictors of survival and patients' satisfaction. The results of the study may enable more Veterans to receive therapy in a VA based dialysis center. The study could lead to a paradigm shift with immediate impact on kidney care in Veterans and in the broader population with ESRD. The study challenges the current standard of care of outright thrice weekly HD in the first year of dialysis therapy, during which patients suffering and mortality are the highest, and is less likely to be supported by for-profit dialysis providers given the perceived reduction in revenue if twice-weekly HD is to be implemented broadly.

Conditions

Chronic Kidney Disease (CKD) Stage 5; Kidney Dysfunction Requiring Dialysis (KDRD); Dialysis Dependency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Twice-Weekly Hemodialysis

Twice-weekly hemodialysis with incremental crossover to thrice-weekly hemodialysis as indicated

Group Type: EXPERIMENTAL

Twice-weekly hemodialysis with incremental crossover to thrice-weekly schedule

Intervention Type: OTHER

50% of the eligible participants will be assigned to twice-weekly hemodialysis for up to 12 months with incremental crossover to thrice-weekly hemodialysis as indicated.

Thrice-Weekly Hemodialysis

Outright thrice-weekly hemodialysis without option to switch to less frequent dialysis schedule

Group Type: PLACEBO_COMPARATOR

Thrice-Weekly Hemodialysis

Intervention Type: OTHER

50% of the eligible participants will be assigned to outright thrice-weekly hemodialysis, which will be continuation of the initial thrice-weekly schedule during the run-in period, without the option to switch to less frequent dialysis schedule representing the standard of care.

Interventions

Twice-weekly hemodialysis with incremental crossover to thrice-weekly schedule

50% of the eligible participants will be assigned to twice-weekly hemodialysis for up to 12 months with incremental crossover to thrice-weekly hemodialysis as indicated.

Intervention Type: OTHER

Thrice-Weekly Hemodialysis

50% of the eligible participants will be assigned to outright thrice-weekly hemodialysis, which will be continuation of the initial thrice-weekly schedule during the run-in period, without the option to switch to less frequent dialysis schedule representing the standard of care.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult Veterans diagnosed with ESRD and who will soon need chronic dialysis initiation or have initiated hemodialysis (HD) not longer than 8 weeks of the target randomization day in one of the six VA centers.
• Meeting the incremental dialysis eligibility criteria in Table 4* under the IncHVets Study Protocol.
• Willingness to undergo the randomly assigned modality of 2x/wk vs 3x/wk HD.
• Willingness to attend the baseline and quarterly study tests in the dialysis unit or via telehealth as determined by study staff, which will mostly be parallel to the routine dialysis clinic visits.
• Agreeable to receive monthly or more frequent reviews for and interviews, regardless of being assigned to the incremental or conventional dialysis group.
• As shown in Table 4 of the INCHVETS Study protocol under incremental dialysis criteria, eligible subjects must have a urine output >0.5 L/day and urea clearance (KRU) >3 ml/min and meet 5 or more of the 9 other incremental dialysis criteria , which are derived from the 2014 Incremental Dialysis Consensus paper (Kalantar-Zadeh et al. Twice-weekly and incremental hemodialysis treatment for initiation of kidney replacement therapy. Am J Kidney Dis. 2014 Aug;64(2):181-6. doi: 10.1053/j.ajkd.2014.04.019. PMID: 24840669 PMCID: PMC4111970)

Exclusion Criteria

• Having a terminal illness with a life expectancy less than 6 months such as stage 4 metastatic cancer or having signed for hospice with life expectancy less than 6 months.
• A serum potassium level >6.0 mEq/L during the 4 weeks prior to the study start.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kamyar Kalantar-Zadeh, MD PhD

Role: PRINCIPAL_INVESTIGATOR

VA Long Beach Healthcare System, Long Beach, CA

Locations

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, United States

Site Status: RECRUITING

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, United States

Site Status: RECRUITING

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, United States

Site Status: RECRUITING

New Mexico VA Health Care System, Albuquerque, NM

Albuquerque, New Mexico, United States

Site Status: RECRUITING

Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY

New York, New York, United States

Site Status: RECRUITING

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kamyar Kalantar-Zadeh, MD PhD

Role: CONTACT

Kamyar.Kalantar-Zadeh@va.gov

(562) 826-8000

Facility Contacts

Kamyar Kalantar-Zadeh, MD PhD

Role: primary

Kamyar.Kalantar-Zadeh@va.gov

562-826-8000

Jeffrey A Kraut, MD

Role: primary

jeffrey.kraut@va.gov

310-478-3711

David Geller, MD

Role: primary

david.geller@va.gov

203-932-5711 ext. 2215

Susan Crowley, MD

Role: backup

susan.crowley@va.gov

2039325711 ext. 2215

Mark L Unruh, MD

Role: primary

MLUnruh@salud.unm.edu

505-272-0600

David S Goldfarb, MD

Role: primary

David.Goldfarb@va.gov

212-686-7500

Csaba P Kovesdy, MD

Role: primary

csaba.kovesdy@va.gov

901-523-8990

Related Links

http://www.INCHVETS.com

INCHVETS study updates and announcements will be posted here

Other Identifiers

CX002382

Identifier Type: OTHER

Identifier Source: secondary_id

NEPH-003-21F

Identifier Type: OTHER

Identifier Source: secondary_id

NEPH-003-21F

Identifier Type: -

Identifier Source: org_study_id