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

NCT04360694 | Recruiting DMC

• 1 other identifier: REAL LIFE
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

End Stage Renal Disease on Dialysis

Outcome Measures

Primary Outcomes (1)

• Number of participants whose kidney function remains >200 ml

  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 Outcomes (10)

• Number of participants who develop cardiovascular death, non fatal myocardial infarction and/or or non fatal stroke (composite outcome)

  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

  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

  12 and 24 months

• Value of residual kidney function (RKF) preservation established by the slope of decline of residual renal urea clearance

  24 months

• Number of people who die

  24 months

Study Arms (2)

Incremental hemodialysis

EXPERIMENTAL

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

Conventional hemodialysis

ACTIVE COMPARATOR

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

Interventions

Incremental hemodialysis PROCEDURE

95 patients will start renal replacement therapy (RRT) with an incremental hemodialysis (once-weekly or twice-weekly) regimen.

Incremental hemodialysis

Conventional hemodialysis PROCEDURE

95 patients will start renal replacement therapy (RRT) with the standard (thrice-weekly) hemodialysis regimen.

Conventional hemodialysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari: lead
• European Renal Association - European Dialysis and Transplant Association: collaborator

Study Sites (1)

Azienda Ospedaliero Universitaria Consorziale Policlinico

Bari, 70124, Italy

RECRUITING

Related Publications (6)

• Casino FG, Basile C. The variable target model: a paradigm shift in the incremental haemodialysis prescription. Nephrol Dial Transplant. 2017 Jan 1;32(1):182-190. doi: 10.1093/ndt/gfw339.

  PMID: 27742823 RESULT

• Basile C, Casino FG, Kalantar-Zadeh K. Is incremental hemodialysis ready to return on the scene? From empiricism to kinetic modelling. J Nephrol. 2017 Aug;30(4):521-529. doi: 10.1007/s40620-017-0391-0. Epub 2017 Mar 23.

  PMID: 28337715 RESULT

• Basile C, Casino FG; EUDIAL Working Group of ERA-EDTA. Incremental haemodialysis and residual kidney function: more and more observations but no trials. Nephrol Dial Transplant. 2019 Nov 1;34(11):1806-1811. doi: 10.1093/ndt/gfz035. No abstract available.

  PMID: 30805639 RESULT

• Casino FG, Basile C. A user-friendly tool for incremental haemodialysis prescription. Nephrol Dial Transplant. 2018 Jun 1;33(6):1074-1075. doi: 10.1093/ndt/gfy081. No abstract available.

  PMID: 29672745 RESULT

• Casino FG, Lopez T. The equivalent renal urea clearance: a new parameter to assess dialysis dose. Nephrol Dial Transplant. 1996 Aug;11(8):1574-81.

  PMID: 8856214 RESULT

• Teruel-Briones JL, Fernandez-Lucas M, Rivera-Gorrin M, Ruiz-Roso G, Diaz-Dominguez M, Rodriguez-Mendiola N, Quereda-Rodriguez-Navarro C. Progression of residual renal function with an increase in dialysis: haemodialysis versus peritoneal dialysis. Nefrologia. 2013;33(5):640-9. doi: 10.3265/Nefrologia.pre2013.May.12038. English, Spanish.

  PMID: 24089155 RESULT

Central Study Contacts

Loreto Gesualdo, MD

CONTACT

+390805594041; loreto.gesualdo@uniba.it

Domenico Roselli, MSc

CONTACT

+390805592778; domenico.roselli@policlinico.ba.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Nephrology University of Bari Aldo Moro - Head of the Nephrology, Dialysis and Transplantation Unit

Model Details: 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). It consists in starting the HD treatment adopting the new incremental approach guided by the VTM. 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. Then, HD sessions will be increased to twice-weekly. When KRU falls bellow 1.5 ml/min/35L, dialysis schedule will change to thrice-weekly, as per criteria for progression. It is controlled through usual clinical practice.

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 24, 2020
• Study Start: May 10, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 12, 2024

Record last verified: 2024-06

Locations

IT (1)