Clinical trial NCT05465044: Incremental Hemodialysis for Veterans in the First Year of Dialysis (IncHVets)
Official title: Incremental Hemodialysis for Veterans in the First Year of Dialysis (IncHVets): A Pragmatic, Multi-Center, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Kidney Disease (CKD) Stage 5
Kidney Dysfunction Requiring Dialysis (KDRD)
Dialysis Dependency
Keywords: chronic kidney disease (CKD)
Residual kidney function (RKF)
Uremia
End-stage Renal Disease (ESRD)
Hemodialysis
Dialysis adequacy
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2022-07-19
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic randomized controlled trial (RCT)
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change over time in numeric scale of Health-Related Quality of Life (HRQOL) Physical Component Score (PCS) of SF36 questionnaire.
timeFrame: Change over 12 months based on measuring at baseline and at Month 3, 6, 9 and 12
Secondary outcomes:
measure: Change over time in numeric scale of SF36 Energy/Fatigue Subscale off SF36 HRQOL
timeFrame: Change over 12 months based on measuring at baseline and at Month 3, 6, 9 and 12
measure: Change over time in in numeric score of Dialysis Symptom Index (DSI)
timeFrame: Change over 12 months based on measuring at baseline and at Month 3, 6, 9 and 12
measure: Change over time in residual urine output (UOP) in ml/day
timeFrame: Change over 12 months based on measuring at baseline and at Month 3, 6, 9 and 12
measure: Change over time in numeric value of Total Dialysis Adequacy (KT/V, sum of dialysis and residual kidney urea clearance)
timeFrame: Change over 12 months based on measuring at baseline and at Month 3, 6, 9 and 12
measure: Change over time in numeric scale of Malnutrition-Inflammation Score (MIS)
timeFrame: Change over 12 months based on measuring at baseline and at Month 3, 6, 9 and 12
measure: Change over time in Serum level of Growth Differentiation Factor 15 (GDF15)
timeFrame: Change over 12 months based on measuring at baseline and at Month 3, 6, 9 and 12
Other outcomes:
measure: Change over time in numeric scale of Short Physical Performance Battery (SPPB)
timeFrame: Change over 12 months based on measuring at baseline and at Month 6, and 12 in the sub-study of 112 participants
measure: Change over time in mid-arm muscle circumference (MAMC) in cm
timeFrame: Change over 12 months based on measuring at baseline and at Month 6, and 12 in the sub-study of 112 participants
measure: Change over time in Left Ventricular (LV) mass
timeFrame: Over 12 months (from baseline and at Month 12) in the sub-study of 112 participants
Locations:
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
city: West Haven
country: United States
facility: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
state: Connecticut
city: Albuquerque
country: United States
facility: New Mexico VA Health Care System, Albuquerque, NM
state: New Mexico
city: New York
country: United States
facility: Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
state: New York
city: Memphis
country: United States
facility: Memphis VA Medical Center, Memphis, TN
state: Tennessee
Study officials:
affiliation: VA Long Beach Healthcare System, Long Beach, CA
name: Kamyar Kalantar-Zadeh, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: