Restrictive Versus Liberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury

NCT ID: NCT05306964

Last Updated: 2025-08-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

99 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-05

Study Completion Date

2024-06-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Critically ill patients with acute kidney injury and fluid overload who are frequently treated by fluid removal during dialysis are at an increased risk of complications and death. Both slower and faster rates of fluid removal may cause injury to the vital organs. This proposed clinical trial will examine the feasibility of restrictive compared with a liberal rate of fluid removal in order to develop effective treatments for fluid overload and to improve the health of critically ill patients.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

"Net ultrafiltration (UFnet)," also known as net fluid removal during kidney replacement therapy, has been used in the treatment of fluid overload among critically ill patients with acute kidney injury (AKI) for more than seven decades. However, the optimal rate of fluid removal (i.e., UFnet rate) remains uncertain, complications such as hypotension and cardiac arrhythmias occur frequently, and more than 40% of patients die. Observational studies in critically ill patients receiving continuous kidney replacement therapy (CKRT) show that UFnet rate has a "J" shaped association with mortality with both slower and faster UFnet rates associated with increased risk of death compared with moderate UFnet rates.

The overall objective of this randomized trial is to establish the feasibility of maintaining patients in the restrictive UFnet rate strategy during treatment with CKRT. The investigator's central hypothesis is that a restrictive UFnet rate strategy embracing a "slow and steady" approach to fluid removal is associated with fewer complications, including cardiac arrhythmias, hypotension, and death, compared with a more liberal "sprint and pause" strategy among critically ill patients.

The trial is a prospective, two-center, unblinded, parallel-group, 2-arm, comparative effectiveness, stepped-wedge cluster-randomized trial among 112 critically ill patients with AKI treated with CKRT in 10 ICUs across two hospital systems. The trial will be conducted at 5 ICUs at University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania, as well as 5 ICUs at Mayo Clinic, Rochester, Minnesota. ICUs will be randomized 1:1 to either a restrictive or a liberal UFnet rate strategy. During the first six months, all ICUs will continue with a liberal UFnet rate strategy. Every two months thereafter or when 10 patients have been enrolled, whichever occurs first, one ICU will be randomized to deploy the restrictive UFnet rate strategy.

In the liberal group, the UFnet rate will be titrated between 2.0-5.0 mL/kg/h and maintained throughout fluid removal. In the restrictive group, the UFnet rate will be titrated between 0.5-1.5 mL/kg/h and maintained throughout fluid removal. The UFnet rates used in both strategies are used in current clinical practice.This feasibility trial will be used to support the rationale and design of a future multicenter phase III randomized trial to examine the effects of alternative UFnet rate strategies on patient-centered clinical outcomes.

Amendment changes- The "Delivered UFnet rates" outcome measure was amended based on a new calculation of effect size when we lowered the sample size from 144 patients to 112 patients in the trial.

The Participant Recruitment Rate Over 21 Months" outcome measure was based on a new sample size estimation when we lowered the sample size from 144 patients to 112 patients in the trial due to slow rate of enrollment in the trial.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Kidney Injury Fluid Overload Hypotension Dialysis; Complications Critical Illness

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, two-center, unblinded, parallel-group, 2-arm, comparative effectiveness, stepped-wedge cluster-randomized trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Restrictive UFnet Strategy

Fluid removal will be titrated to keep net ultrafiltration rate between 0.5-1.5 mL/kg/h

Group Type ACTIVE_COMPARATOR

Restrictive UFnet Rate Strategy

Intervention Type PROCEDURE

In the restrictive group, the UFnet rate will be titrated between 0.5-1.5 mL/kg/h and maintained throughout fluid removal.

Liberal UFnet Strategy

Fluid removal will be titrated to keep net ultrafiltration rate between 2.0-5.0 mL/kg/h

Group Type ACTIVE_COMPARATOR

Liberal UFnet Rate Strategy

Intervention Type PROCEDURE

In the liberal group, the UFnet rate will be titrated between 2.0-5.0 mL/kg/h and maintained throughout fluid removal.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Restrictive UFnet Rate Strategy

In the restrictive group, the UFnet rate will be titrated between 0.5-1.5 mL/kg/h and maintained throughout fluid removal.

Intervention Type PROCEDURE

Liberal UFnet Rate Strategy

In the liberal group, the UFnet rate will be titrated between 2.0-5.0 mL/kg/h and maintained throughout fluid removal.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Age 18 years or older
2. Stage 3 acute kidney injury according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria
3. Started or intending to start CKRT for volume management
4. Attending intensivist or nephrologist intending to remove net fluid using CKRT for at least 48 hours

Exclusion Criteria

1. Respiratory distress due to pulmonary edema or fluid overload in unintubated patients
2. Massive volume infusion (i.e., \>200 mL/h for \>6 hours of continuous infusion)
3. No intention to remove net fluid as determined by attending intensivist or nephrologist
4. Attending intensivist or nephrologist believes that the protocol will not be followed
5. Continuous net fluid removal for \>48 hours prior to study enrollment
6. Patients on chronic outpatient hemodialysis
7. Patients with history of, or current admission for kidney transplantation
8. Patients on comfort measures only orders.
9. Moribund not expected to survive \>24 hours
10. Confirmed pregnancy
11. Patients treated with extracorporeal membrane oxygenation, ventricular assist device, or intra-aortic balloon pump
12. Organ donors with neurological determination of death (i.e., brain dead donors)
13. Drug overdose requiring CKRT for drug clearance
14. Enrollment in a concurrent interventional clinical trial with direct impact on fluid balance (e.g., \>500 mL study drug administration)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Mayo Clinic

OTHER

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Raghavan Murugan

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Raghavan Murugan, MD, MS, FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Mayo Clinic

Rochester, Minnesota, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Murugan R, Kerti SJ, Chang CH, Gallagher M, Clermont G, Palevsky PM, Kellum JA, Bellomo R. Association of Net Ultrafiltration Rate With Mortality Among Critically Ill Adults With Acute Kidney Injury Receiving Continuous Venovenous Hemodiafiltration: A Secondary Analysis of the Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy Trial. JAMA Netw Open. 2019 Jun 5;2(6):e195418. doi: 10.1001/jamanetworkopen.2019.5418.

Reference Type BACKGROUND
PMID: 31173127 (View on PubMed)

Murugan R, Balakumar V, Kerti SJ, Priyanka P, Chang CH, Clermont G, Bellomo R, Palevsky PM, Kellum JA. Net ultrafiltration intensity and mortality in critically ill patients with fluid overload. Crit Care. 2018 Sep 24;22(1):223. doi: 10.1186/s13054-018-2163-1.

Reference Type BACKGROUND
PMID: 30244678 (View on PubMed)

Serpa Neto A, Naorungroj T, Murugan R, Kellum JA, Gallagher M, Bellomo R. Heterogeneity of Effect of Net Ultrafiltration Rate among Critically Ill Adults Receiving Continuous Renal Replacement Therapy. Blood Purif. 2021;50(3):336-346. doi: 10.1159/000510556. Epub 2020 Oct 7.

Reference Type BACKGROUND
PMID: 33027799 (View on PubMed)

Naorungroj T, Neto AS, Zwakman-Hessels L, Yanase F, Eastwood G, Murugan R, Kellum JA, Bellomo R. Early net ultrafiltration rate and mortality in critically ill patients receiving continuous renal replacement therapy. Nephrol Dial Transplant. 2021 May 27;36(6):1112-1119. doi: 10.1093/ndt/gfaa032.

Reference Type BACKGROUND
PMID: 32259841 (View on PubMed)

Naorungroj T, Neto AS, Zwakman-Hessels L, Fumitaka Y, Eastwood G, Murugan R, Kellum JA, Bellomo R. Mediators of the Impact of Hourly Net Ultrafiltration Rate on Mortality in Critically Ill Patients Receiving Continuous Renal Replacement Therapy. Crit Care Med. 2020 Oct;48(10):e934-e942. doi: 10.1097/CCM.0000000000004508.

Reference Type BACKGROUND
PMID: 32885938 (View on PubMed)

Murugan R, Ostermann M, Peng Z, Kitamura K, Fujitani S, Romagnoli S, Di Lullo L, Srisawat N, Todi S, Ramakrishnan N, Hoste E, Puttarajappa CM, Bagshaw SM, Weisbord S, Palevsky PM, Kellum JA, Bellomo R, Ronco C. Net Ultrafiltration Prescription and Practice Among Critically Ill Patients Receiving Renal Replacement Therapy: A Multinational Survey of Critical Care Practitioners. Crit Care Med. 2020 Feb;48(2):e87-e97. doi: 10.1097/CCM.0000000000004092.

Reference Type BACKGROUND
PMID: 31939807 (View on PubMed)

Murugan R, Bellomo R, Palevsky PM, Kellum JA. Ultrafiltration in critically ill patients treated with kidney replacement therapy. Nat Rev Nephrol. 2021 Apr;17(4):262-276. doi: 10.1038/s41581-020-00358-3. Epub 2020 Nov 11.

Reference Type BACKGROUND
PMID: 33177700 (View on PubMed)

Lumlertgul N, Murugan R, Seylanova N, McCready P, Ostermann M. Net ultrafiltration prescription survey in Europe. BMC Nephrol. 2020 Dec 1;21(1):522. doi: 10.1186/s12882-020-02184-y.

Reference Type BACKGROUND
PMID: 33256635 (View on PubMed)

Chen H, Murugan R. Survey of U.S. Critical Care Practitioners on Net Ultrafiltration Prescription and Practice among Critically Ill Patients Receiving Kidney Replacement Therapy. J Crit Care Med (Targu Mures). 2021 Nov 6;7(4):272-282. doi: 10.2478/jccm-2021-0034. eCollection 2021 Oct.

Reference Type BACKGROUND
PMID: 34934817 (View on PubMed)

Tehranian S, Shawwa K, Kashani KB. Net ultrafiltration rate and its impact on mortality in patients with acute kidney injury receiving continuous renal replacement therapy. Clin Kidney J. 2019 Dec 17;14(2):564-569. doi: 10.1093/ckj/sfz179. eCollection 2021 Feb.

Reference Type BACKGROUND
PMID: 33623680 (View on PubMed)

Naorungroj T, Serpa Neto A, Murugan R, Kellum JA, Bellomo R. Continuous Renal Replacement Therapy: The Interaction between Fluid Balance and Net Ultrafiltration. Am J Respir Crit Care Med. 2021 May 1;203(9):1199-1201. doi: 10.1164/rccm.202011-4097LE. No abstract available.

Reference Type BACKGROUND
PMID: 33513318 (View on PubMed)

Kitamura K, Hayashi K, Fujitani S, Murugan R, Suzuki T. Ultrafiltration in Japanese critically ill patients with acute kidney injury on renal replacement therapy. J Intensive Care. 2021 Dec 20;9(1):77. doi: 10.1186/s40560-021-00590-4.

Reference Type BACKGROUND
PMID: 34930481 (View on PubMed)

Murugan R, Chang CH, Raza M, Nikravangolsefid N, Huang DT, Palevsky PM, Kashani K; (RELIEVE-AKI) Study Investigators. Restrictive versus Liberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury (RELIEVE-AKI): a pilot clinical trial protocol. BMJ Open. 2023 Jul 7;13(7):e075960. doi: 10.1136/bmjopen-2023-075960.

Reference Type DERIVED
PMID: 37419639 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

1R01DK128100-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY21080010

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Exploring Water-free Sodium Storage
NCT06872645 RECRUITING NA
The ECMO-Free Trial
NCT05486559 ENROLLING_BY_INVITATION NA
Fluid Volume During Fluid Shifts
NCT03447574 COMPLETED NA