RandomizEd ClinicAL triaL on the Efficacy and saFety of Incremental Hemodialysis (REAL-LIFE)

June 11, 2024 updated by: Loreto Gesualdo, MD, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari

RandomizEd ClinicAL triaL on the Efficacy and saFety of Incremental Hemodialysis

Background: The thrice-weekly hemodialysis (HD) regimen is widely accepted as a standard prescription. The concept of incremental dialysis has been established as a possible alternative for patients with preserved diuresis and end-stage renal failure in need of HD. The main problems related to prescription of incremental HD are an arbitrary use of infrequent regimens and the lack of clear standards for incorporating residual kidney function (RKF) in the assessment of HD dose. Several models have been proposed for prescription of incremental dialysis. The latest, the variable target model (VTM), gives more clinical weight to the RKF and allows less frequent HD treatments at lower RKF. Despite increasing evidence derived from observational studies to support the use of incremental HD, RCTs are lacking and, therefore, urgently needed.

Methods/Design:

The Department of Nephrology, Dialysis and Transplantation of the Azienda Ospedaliero Universitaria Consorziale Policlinico, Bari, Italy and the EUDIAL Working Group of the European Renal Association - European Dialysis Transplant Association (ERA-EDTA) are starting a randomized clinical trial (RCT) in incident HD patients, whose name is "REAL LIFE", by using the acronym of its whole definition: RandomizEd clinicAL triaL on the effIcacy and saFety of incremental haEmodialysis. REAL LIFE is a pragmatic, prospective, multicentre, open label RCT, investigator-initiated, comparing the intervention arm (incremental HD) with the control arm (standard 3HD/wk). The trial, originally conceived by experts at the Division of Nephrology of the Miulli General Hospital, Acquaviva delle Fonti, Italy, consists in starting the HD treatment adopting the new incremental approach guided by the VTM. The primary outcome is the survival of kidney function, with the event defined as urinary output (UO) ≤ 200 mL/day, confirmed by a further collection after 2 weeks to exclude temporary illness.

Discussion: REAL LIFE will enable the investigators to know with the highest level of scientific evidence the safety and efficacy of an incremental approach to the start of HD treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The majority of dialysis patients starting hemodialysis (HD) are currently treated with a fixed dose thrice-weekly HD (3HD/wk). The 3HD/wk regimen has been assumed, until recently, almost as a dogma in the dialysis community. Incremental HD is based on the simple idea of adjusting its dose according to the metrics of RKF. REAL LIFE is a pragmatic, prospective, multicentre, open label RCT, investigator-initiated, comparing the intervention arm (incremental HD) with the control arm (standard 3HD/wk). A Variable Target Model (VTM) has been suggested, which gives more clinical weight to the RKF and allows less frequent HD treatments in patients with lower RKF. The investigators recommend to start and keep on with once-weekly HD, which should be possible until residual renal urea clearance (KRU) falls below 2.5 - 3.0 mL/min/35 L, i.e., glomerular filtration rate (GFR) ≈ 4 mL/min/1.73 m2.

The primary outcome is the survival of kidney function, with the event defined as urinary output (UO) ≤ 200 mL/day, confirmed by a further collection after 2 weeks to exclude temporary illness. Secondary outcomes are: composite primary cardiovascular endpoint (cardiovascular death, non fatal myocardial infarction and/or or non fatal stroke); intima-media thickness of the carotid arteries; specific cardiomyopathy control; RKF preservation; patients survival; hospital admissions; anemia control; mineral and bone disorder control, and middle molecules removal.

The sample size calculation is based on the primary outcome "presence of anuria". The assumptions for calculating the sample size, derived from data of Teruel Briones et al., are the following:

  • Percentage of subjects who developed anuria in the experimental group (incremental HD): 25%
  • Percentage of subjects who developed anuria in the control group (standard 3HD/wk): 51%
  • Power: 0.8
  • Ratio: 1:1
  • Non-compliance: 20%
  • Total expected sample size: 190 (95 participants in each group)

The assessment of the key kinetic parameters as well as the guide to the selection of operative parameters, as required to get the required equilibrated Kt/V (eKt/V = 1.05), will be done by using SPEEDY, a spreadsheet prescription tool that uses essentially the same equations used by Solute Solver, the software based on the double pool UKM recommended by the 2015 KDOQI guidelines. SPEEDY is freely available at the European Nephrology Portal (ENP).

The link is https://enp-era-edta.org/174/page/home. The control arm includes patients put on a thrice-weekly HD schedule, as detailed above. The dialysis dose (eKt/V) should be about 1.05.

PICO question:

Participants with CKD-EPI GFR ≤ 10 ml/min and daily urine output > 600 ml Intervention: one or two weekly hemodialysis (as detailed above) Comparator: three weekly hemodialysis (as per standard practice and as detailed above) Outcome: Residual renal function

Study Type

Interventional

Enrollment (Estimated)

190

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged > 18 years
  • Start of maintenance hemodialysis treatment due to advanced CKD stage 5D
  • Patients who are about to start HD or have already started HD within a period of ≤ 2 weeks
  • Glomerular filtration rate <= 10 mL/min/1.73 m2, as estimated by means of CKD-EPI formula.

Exclusion Criteria:

  • Age < 18 years
  • Acute kidney injury or acute on chronic kidney injury
  • eGFR higher than 10 mL/min/1.73 m2
  • UO < 600 mL/day
  • Already treated with other replacement therapies (peritoneal dialysis or kidney transplant)
  • Unable or unwilling to give informed consent.
  • Unable to comply with trial procedures, e.g., collection of UO.
  • Likely survival prognosis or planned modality or centre transfer < 6 months.
  • Patients who are in the waiting list for a living kidney transplant
  • Associated diseases: active neoplastic disease; refractory congestive heart failure (type IV NYHA, ejection fraction ≤ 30%) requiring high ultrafiltration volumes per session.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Incremental hemodialysis
Procedure: Incremental hemodialysis. It consists in reducing the frequency or number of sessions per week with which patients start the HD treatment. The experimental group will start with one session/week, then the number of weekly sessions will be increased to two and later to three as per criteria for progression
Procedure: Incremental hemodialysis
95 patients will start renal replacement therapy (RRT) with an incremental hemodialysis (once-weekly or twice-weekly) regimen.
Active Comparator: Conventional hemodialysis
Procedure: Conventional hemodialysis. It is controlled through usual clinical practice, based on starting the HD treatment with three sessions per week (control group).
Procedure: Conventional hemodialysis
95 patients will start renal replacement therapy (RRT) with the standard (thrice-weekly) hemodialysis regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants whose kidney function remains >200 ml
Time Frame: 24 months
The survival of kidney function is defined as a time to the event (anuria): the anuria is defined as urinary output (UO) ≤ 200 mL/day, confirmed by a further collection after 2 weeks to exclude temporary illness
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who develop cardiovascular death, non fatal myocardial infarction and/or or non fatal stroke (composite outcome)
Time Frame: 24 months
Cardiovascular death, non fatal myocardial infarction and/or or non fatal stroke
24 months
Mean value of intima-media thickness of the carotid arteries of participants at end of treatment and change from beginning to end of treatment
Time Frame: 12 and 24 months
Echographic evaluation of intima-media thickness of the carotid arteries
12 and 24 months
Value of left ventricular ejection fraction established with cardiac ultrasound at end of treatment and change from beginning to end of treatment
Time Frame: 12 and 24 months
Ecocardiography reporting data on the left ventricular ejection fraction (LVEF)
12 and 24 months
Value of residual kidney function (RKF) preservation established by the slope of decline of residual renal urea clearance
Time Frame: 24 months
The rate of decline in RKF defined as the slope of decline of residual renal urea clearance
24 months
Number of people who die
Time Frame: 24 months
The follow-up time will be determined in days. It will be defined as the difference in days from the date of the end of the follow-up minus the date of the baseline visit. Events will be counted either as deaths (follow-up of less than 24 months) or as end of the follow-up
24 months
Number of people who are hospitalized
Time Frame: 24 months
The number of admissions will be registered.
24 months
Value of hemoglobin in participants at end of treatment and change from beginning to end of treatment
Time Frame: Every month
The hemoglobin levels (in g/dl) will be measured.
Every month
Value of serum phosphorus, calcium and parathyroid hormone in participants at end of treatment and change from beginning to end of treatment
Time Frame: Every month and three months
Serum phosphorus and calcium levels (in mg/dl), and intact PTH (in pg/dl) will be measured.
Every month and three months
Value of serum beta 2 microglobulin (middle molecule) at end of treatment and change from beginning to end of treatment
Time Frame: Every three months
The rate of change in serum beta 2 microglobulin in time will be evaluated
Every three months
Value of p-cresyl sulfate and inoxyl sulfate at end of treatment and change from beginning to end of treatment (uraemic toxins variation)
Time Frame: Every six months
Variation of uremic toxins including p-cresyl sulfate and inoxyl sulfate
Every six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari

Collaborators

European Renal Association - European Dialysis and Transplant Association

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2021

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

April 17, 2020

First Submitted That Met QC Criteria

April 21, 2020

First Posted (Actual)

April 24, 2020

Study Record Updates

Last Update Posted (Actual)

June 12, 2024

Last Update Submitted That Met QC Criteria

June 11, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REAL LIFE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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