Clinical trial NCT06141798: Twice vs Thrice Weekly Incident Hemodialysis in Elderly Patients
Official title: A Pragmatic Randomized Clinical Trial: Twice-weekly vs Thrice-weekly Incident hemoDialysis in Elderly Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Age Problem
Dialysis; Complications
Frailty
Quality of Life
Lead sponsor: Soonchunhyang University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health & Welfare, Korea
First posted: 2023-11-21
Enrollment: 428
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic Randomization Trial
Primary purpose: TREATMENT

Brief summary: As Korea is becoming a super-aged society, the number of elderly patients with end-stage kidney disease (ESKD) is expected to increase rapidly. Therefore, the burden on Korean society will also increase.

Thrice-weekly hemodialysis is standard for renal replacement therapy. However, this regimen has not been validated for elderly ESKD patients with residual renal function. Elderly patients can have multiple comorbidities such as hypertension, diabetes, cardiovascular disease, and impaired physical activity. Frequent hemodialysis could provoke falls, hypotension, and cognitive impairment. Previous reports have suggested the potential benefit of twice-weekly hemodialysis with incremental increases in frequency when residual renal function decreases. In addition, twice-weekly hemodialysis decreases hospitalization rates in frail patients.

Therefore, the investigators hypothesized initiating renal replacement therapy with twice-weekly hemodialysis decreases the hopsitalizatoin rates compared with conventional thrice-weekly hemodialysis in elderly ESRD patients with residual renal function. This study is a pragmatic randomized clinical trial, multicenter study. Study subjects are incident ESRD patients (\>= 60 years old, n=428) with residual urine volume ( \> 500 mL/day) and follow up up to 2 years. Twice-weekly hemodialysis could be incremented according to clinical situations such as volume overload, hyperkalemia and uremic symptom. Primary outcome of this study is hospitalization rate during follow-up. Secondary outcomes include dialysis related hospitalization rate, the length of hospital stay, complication of dialysis,mortality rate and assessments of quality of life, frailty, and cost-utility.

Detailed description: End-stage kidney disease (ESKD) poses a substantial public health challenge, with the number of patients requiring renal replacement therapy (RRT) globally reaching 2.61 million in 2010 and projected to rise to 5.43 million by 2030. In Korea, the incidence of hemodialysis (HD) has also been gradually increasing. The increase in HD incidence in South Korea is significantly linked to the aging population. Korea is one of the most rapidly aging countries in the world and the age of dialysis patients is also increasing, with more than half over the age of 60.

HD has potential advantages over conservative management or peritoneal dialysis in older adults, however, guidelines for optimal HD for the elderly have not yet been established. Typically, patients receive HD three times a week, with only a small proportion of patients receiving less frequent dialysis. However, potential disadvantages such as hemodynamic stress, vascular access problems, bleeding, falls and economic cost should be considered in older adults with ESKD.

In elderly patients, it is often difficult to maintain a thrice-weekly HD schedule due to the presence of other medical conditions and the challenges of frailty. Elderly patients have shown poor outcome even after initiation of HD. A study by Santos et al. demonstrated a more than twofold increased risk of mortality at 6 months in patients older than 75 years compared to those younger than 75. Another study using Japanese National Dialysis Registry data revealed a 30% mortality rate in those aged over 80 years within 1 year after initiation of HD, with frailty being one of the most important factors associated with early death after initiation of HD. Excessive HD in elderly patients can lead to malnutrition, low blood pressure during dialysis, poor quality of life, depression, and stress due to physical and temporal activity restriction. The increased risk of falls in HD patients is also a serious problem.

Incremental initiation of HD involves starting HD at a lower intensity than the standard 4 hours thrice weekly and gradually increasing the frequency and duration of dialysis as kidney function declines. The decision to initiate patients on incremental HD can be made based on clinical parameters such as urine volume or residual kidney function, socio-economic factors such as financial limitations or insurance coverage, or lack of availability of dialysis services. Current guidelines recommend that twice weekly dialysis be performed in patients with kidney urea clearance greater than 3ml/min/1.73m2 or a urine output over 0.5 liter per day.

A systemic review and meta-analysis showed no difference in mortality, hospitalization rates, or quality of life between patients receiving incremental and conventional HD, with improved preservation of residual renal function and a reduction in dialysis cost with incremental HD. One randomized controlled trial (RCT) showed no difference in episodes of fluid overload or hyperkalemia, but an increased risk of hyperkalemia with incremental HD. Another study showed lower hospitalization rate in incremental HD compared to conventional dialysis. These studies demonstrate the need for a large RCT comparing incremental and conventional HD.

However, current studies do not provide conclusive evidence on the benefits and risks of incremental HD in elderly patients. Therefore, the investigators are conducting a pragmatic RCT to determine whether the initiation of renal replacement therapy with twice-weekly HD reduces hospitalization rates compared to conventional thrice-weekly HD in older adults with ESKD.

Trial design PRIDE trial is designed as a pragmatic RCT comparing the effect of initiating twice-weekly hemodialysis with an incremental approach compared to thrice-weekly HD on hospitalization rates in elderly ESKD patients with RKF. A total of 428 participants will be recruited from 18 academic dialysis centers in Korea. Participants will have the flexibility to transfer to other dialysis centers as needed. The decision to increase dialysis frequency will be made by the treating physicians.

Hypothesis Our main hypothesis is that twice-weekly HD, when prescribed to older adults with RKF will reduce hospitalization rates compared with thrice-weekly HD.

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Eligibility criteria: Inclusion Criteria:

* Age ≥60 years
* Clinical diagnosis of end stage kidney disease
* Starting maintenance hemodialysis within one month
* 24-hour urine output ≥ 500 ml at randomization
* Sufficient understanding of the study procedures and requirements.

Exclusion Criteria:

* Left ventricular ejection fraction \< 40%)
* Liver cirrhosis
* Current treatment for an active malignancy or active infection
* Onability or refusal to provide written informed consent
* enrollment in another clinical trial.

Primary outcomes:
measure: Hospitalization rate
timeFrame: Follow up: 2 years
Secondary outcomes:
measure: Dialysis related hospitalization rate
timeFrame: Follow up: 2 years
measure: Length of Hospital Stay
timeFrame: Follow up: 2 years
measure: Complication of dialysis
timeFrame: Follow up: 2 years
measure: Mortality rate
timeFrame: Follow up: 2 years
measure: The Clinical Frailty Scale
timeFrame: Follow up: 2 years
measure: Cost effective
timeFrame: Follow up: 2 years
measure: Kidney Disease Quality of Life Instrument (KDQOL)
timeFrame: Follow up: 2 years
Other outcomes:
Locations:
city: Bucheon
country: Korea, Republic of
facility: Soonchunhyang University Hospital Bucheon
city: Chuncheon
country: Korea, Republic of
facility: Hallym University Medical Center- Chuncheon
city: Seoul
country: Korea, Republic of
facility: Soonchunhyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Koera University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido St. Mary's Hospital
city: Wŏnju
country: Korea, Republic of
facility: Yonsei University, Wonju Severance Christian Hospital
Study officials:
affiliation: Soonchunhyang University Hospital
name: Soon Hyo Kwon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Han M, Jeon H, Yu BC, Song SH, Chung S, Lim C, Sohn H, Noh JW, Kwon SH; PRIDE Research Group. A Pragmatic Randomized clinical trial: twice-weekly vs. thrice-weekly Incident hemoDialysis in Elderly patients (PRIDE): study protocol. Kidney Res Clin Pract. 2023 Dec 18. doi: 10.23876/j.krcp.23.177. Online ahead of print.