Acute Kidney InjuryRELIEVE-AKINCT05306964
Restrictive Versus Liberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury
A study testing Restrictive UFnet Rate Strategy and Liberal UFnet Rate Strategy in people with Acute Kidney Injury and Fluid Overload, run by University of Pittsburgh at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury, Fluid Overload, Hypotension
- What is being tested?
- Restrictive UFnet Rate Strategy and Liberal UFnet Rate Strategy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 Jul 2022to 26 Jun 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Stage 3 acute kidney injury according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria
- Started or intending to start CKRT for volume management
- Attending intensivist or nephrologist intending to remove net fluid using CKRT for at least 48 hours
Who cannot join
- Respiratory distress due to pulmonary edema or fluid overload in unintubated patients
- Massive volume infusion (i.e., >200 mL/h for >6 hours of continuous infusion)
- No intention to remove net fluid as determined by attending intensivist or nephrologist
- Attending intensivist or nephrologist believes that the protocol will not be followed
- Continuous net fluid removal for >48 hours prior to study enrollment
- Patients on chronic outpatient hemodialysis
Show all 14Show fewer
- Patients with history of, or current admission for kidney transplantation
- Patients on comfort measures only orders.
- Moribund not expected to survive >24 hours
- Confirmed pregnancy
- Patients treated with extracorporeal membrane oxygenation, ventricular assist device, or intra-aortic balloon pump
- Organ donors with neurological determination of death (i.e., brain dead donors)
- Drug overdose requiring CKRT for drug clearance
- Enrollment in a concurrent interventional clinical trial with direct impact on fluid balance (e.g., >500 mL study drug administration)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15261
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: REstrictive Versus LIberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury
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.
Read the detailed description
"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
- Acute Kidney Injury, Fluid Overload, Hypotension, Dialysis; Complications, Critical Illness
- Being tested
- Restrictive UFnet Rate Strategy, Liberal UFnet Rate Strategy
- Keywords
- Fluid overload, Acute kidney injury, Net ultrafiltration, Intensive care unit, Intradialytic hypotension, Complications, Feasibility Trial, Cardiac arrhythmias, Mortality, Dialysis dependence
- Medical subject headings
- Acute Kidney Injury, Edema, Hypotension, Critical Illness, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Restrictive UFnet Rate StrategyProcedure or surgery
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 Rate StrategyProcedure or surgery
In the liberal group, the UFnet rate will be titrated between 2.0-5.0 mL/kg/h and maintained throughout fluid removal.
| Study group | Role | What they receive |
|---|---|---|
| Restrictive UFnet Strategy | Active comparator | Fluid removal will be titrated to keep net ultrafiltration rate between 0.5-1.5 mL/kg/h Receives: Procedure: Restrictive UFnet Rate Strategy |
| Liberal UFnet Strategy | Active comparator | Fluid removal will be titrated to keep net ultrafiltration rate between 2.0-5.0 mL/kg/h Receives: Procedure: Liberal UFnet Rate Strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delivered UFnet Rates.
A minimum separation of 0.53-0.57 mL/kg/h in mean delivered UFnet rates between the two intervention arms.
Measured: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.
No. of Participants With Protocol Deviation.
Protocol deviation defined as delivered UFnet rate that lies >0.5 mL/kg/h outside of the target UFnet rate range for greater than six consecutive hours.
Measured: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.
Participant Recruitment/ICU/ 2 Months
An enrollment rate of 1 patient per ICU per time period.
Measured: 24 months
Secondary outcomes (9)
Daily Fluid Balance (Average)
Patient daily fluid balance will be measured while on continuous kidney replacement therapy and reported as average across all study days.
Measured: Average daily fluid balance from enrollment to ICU discharge or until day 28, whichever occurs first.
Cumulative Fluid Balance
Patient cumulative fluid balance will be measured while on continuous kidney replacement therapy.
Measured: Daily from enrollment to ICU discharge or until day 28, whichever occurs first.
Duration of Kidney Replacement Therapy
The number of days the patient received kidney replacement therapy while in the hospital.
Measured: Daily from enrollment to hospital discharge or until day 28, whichever occurs first.
Duration of Mechanical Ventilation
The number of days the patient received mechanical ventilation while in hospital.
Measured: Daily from study enrollment to ICU discharge or until day 28, whichever occurs first.
Organ Failure Free Days
The no. of days the patient remained free of organ failure while in the ICU.
Measured: Daily from study enrollment to ICU discharge or until day 28, whichever occurs first.
ICU Length of Stay
The number of days patients need to stay in the ICU
Measured: Daily from study enrollment to ICU discharge or day 28, whichever occurs first.
Hospital Length of Stay
The number of days patients need to stay in the hospital
Measured: Daily from study enrollment to hospital discharge or day 28.
Hospital Mortality
The proportion of patients who died while in the hospital.
Measured: From study enrollment to hospital discharge or day 28, whichever occurs first.
Dependence on Kidney Replacement Therapy
The proportion of patients who were on dialysis at hospital discharge.
Measured: From study enrollment until hospital discharge or day 28, whichever occurs first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study start5 Jul 2022
- Primary completion17 Jun 2024
- Study completion26 Jun 2024
Why it stopped: The trial was terminated due to insufficient funds.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, two-center, unblinded, parallel-group, 2-arm, comparative effectiveness, stepped-wedge cluster-randomized trial.
- Masking
- None (open label)
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raghavan Murugan, University of Pittsburgh
- Investigators
- Raghavan Murugan, MD, MS, FRCP, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05306964
- Sponsor's protocol ID
- STUDY21080010
- Other IDs
- 1R01DK128100-01A1
- Acronym
- RELIEVE-AKI
- Status last verified
- Aug 2025
- First submitted
- 2 Mar 2022
- Last updated
- 29 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The RELIEVE-AKI study investigators will review the request for data from other investigators. The investigators will execute a data-sharing agreement with the University of Pittsburgh to share de-identified data with other investigators for research purposes only. The data-sharing agreement will ensure: i.) a commitment to using the data only for research purposes and not to identify any individual participant; ii.) a commitment to securing the data using appropriate computer technology; and iii.) a commitment to destroying or returning the data after analyses are completed on a specific date. The investigators will not release any patient identifiers in any of the data files shared with other researchers. The investigators will also require appropriate confidentiality agreements and approvals from the Institutional Review Boards of other investigators before the data are shared.
Publications
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.
PubMed 31173127Murugan 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.
PubMed 30244678Serpa 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.
PubMed 33027799Naorungroj 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.
PubMed 32259841Naorungroj 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.
PubMed 32885938Murugan 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.
PubMed 31939807Murugan 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.
PubMed 33177700Lumlertgul 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.
PubMed 33256635Chen 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.
PubMed 34934817Tehranian 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.
PubMed 33623680Naorungroj 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.
PubMed 33513318Kitamura 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.
PubMed 34930481Murugan R, Talisa V, Chang CH, Nikravangolsefid N, Singh W, Butcher BW, Al-Khafaji A, Gunn S, Abdulmajeed F, Lamberty P, Huang D, Palevsky PM, Kashani K; Restrictive versus Liberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury (RELIEVE-AKI) Study Investigators. Alternative net ultrafiltration rate strategies in acute kidney injury: a feasibility randomized clinical trial. Crit Care. 2026 Apr 22;30(1):228. doi: 10.1186/s13054-026-06040-7.
PubMed 42021350Murugan 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.
PubMed 37419639
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REstrictive Versus LIberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury
- ClinicalTrials.gov ID
- NCT05306964
- Acronym / sponsor ID
- RELIEVE-AKI / STUDY21080010
- Conditions
- Acute Kidney Injury, Fluid Overload, Hypotension, Dialysis; Complications, Critical Illness
- Keywords
- Fluid overload, Acute kidney injury, Net ultrafiltration, Intensive care unit, Intradialytic hypotension, Complications, Feasibility Trial, Cardiac arrhythmias
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was terminated due to insufficient funds.
- Enrolment
- 99 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Mayo Clinic, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 5 Jul 2022 (actual)
- Primary completion
- 17 Jun 2024 (actual)
- Study completion
- 26 Jun 2024 (actual)
- First posted
- 1 Apr 2022 (actual)
- Results
- Posted 29 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
"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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, two-center, unblinded, parallel-group, 2-arm, comparative effectiveness, stepped-wedge cluster-randomized trial.
| Arm | Type | Receives |
|---|---|---|
| Restrictive UFnet Strategy | Active comparator | Procedure: Restrictive UFnet Rate StrategyFluid removal will be titrated to keep net ultrafiltration rate between 0.5-1.5 mL/kg/h |
| Liberal UFnet Strategy | Active comparator | Procedure: Liberal UFnet Rate StrategyFluid removal will be titrated to keep net ultrafiltration rate between 2.0-5.0 mL/kg/h |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 years or older
- Stage 3 acute kidney injury according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria
- Started or intending to start CKRT for volume management
- Attending intensivist or nephrologist intending to remove net fluid using CKRT for at least 48 hours
Key exclusion criteria (14 listed)
- Respiratory distress due to pulmonary edema or fluid overload in unintubated patients
- Massive volume infusion (i.e., >200 mL/h for >6 hours of continuous infusion)
- No intention to remove net fluid as determined by attending intensivist or nephrologist
- Attending intensivist or nephrologist believes that the protocol will not be followed
- Continuous net fluid removal for >48 hours prior to study enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Restrictive UFnet Rate StrategyIn the restrictive group, the UFnet rate will be titrated between 0.5-1.5 mL/kg/h and maintained throughout fluid removal. | Procedure or surgery | Restrictive UFnet Strategy |
| Liberal UFnet Rate StrategyIn the liberal group, the UFnet rate will be titrated between 2.0-5.0 mL/kg/h and maintained throughout fluid removal. | Procedure or surgery | Liberal UFnet Strategy |
Primary outcome
Delivered UFnet Rates.
Time frame: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.
A minimum separation of 0.53-0.57 mL/kg/h in mean delivered UFnet rates between the two intervention arms.
No. of Participants With Protocol Deviation.
Time frame: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.
Protocol deviation defined as delivered UFnet rate that lies >0.5 mL/kg/h outside of the target UFnet rate range for greater than six consecutive hours.
Participant Recruitment/ICU/ 2 Months
Time frame: 24 months
An enrollment rate of 1 patient per ICU per time period.
9 secondary outcomes
Daily Fluid Balance (Average)
Time frame: Average daily fluid balance from enrollment to ICU discharge or until day 28, whichever occurs first.
Cumulative Fluid Balance
Time frame: Daily from enrollment to ICU discharge or until day 28, whichever occurs first.
Duration of Kidney Replacement Therapy
Time frame: Daily from enrollment to hospital discharge or until day 28, whichever occurs first.
Duration of Mechanical Ventilation
Time frame: Daily from study enrollment to ICU discharge or until day 28, whichever occurs first.
Organ Failure Free Days
Time frame: Daily from study enrollment to ICU discharge or until day 28, whichever occurs first.
ICU Length of Stay
Time frame: Daily from study enrollment to ICU discharge or day 28, whichever occurs first.
Hospital Length of Stay
Time frame: Daily from study enrollment to hospital discharge or day 28.
Hospital Mortality
Time frame: From study enrollment to hospital discharge or day 28, whichever occurs first.
Dependence on Kidney Replacement Therapy
Time frame: From study enrollment until hospital discharge or day 28, whichever occurs first.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31173127Murugan 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.
- Background: PubMed 30244678Murugan 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.
- Background: PubMed 33027799Serpa 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.
- Background: PubMed 32259841Naorungroj 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.
- Background: PubMed 32885938Naorungroj 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.
- Background: PubMed 31939807Murugan 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.
- Background: PubMed 33177700Murugan 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.
- Background: PubMed 33256635Lumlertgul 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.
- Background: PubMed 34934817Chen 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.
- Background: PubMed 33623680Tehranian 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.
- Background: PubMed 33513318Naorungroj 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.
- Background: PubMed 34930481Kitamura 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.
- Individual participant dataSharing planned: Yes. The RELIEVE-AKI study investigators will review the request for data from other investigators. The investigators will execute a data-sharing agreement with the University of Pittsburgh to share de-identified data with other investigators for research purposes only. The data-sharing agreement will ensure: i.) a commitment to using the data only for research purposes and not to identify any individual participant; ii.) a commitment to securing the data using appropriate computer technology; and iii.) a commitment to destroying or returning the data after analyses are completed on a specific date. The investigators will not release any patient identifiers in any of the data files shared with other researchers. The investigators will also require appropriate confidentiality agreements and approvals from the Institutional Review Boards of other investigators before the data are shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raghavan Murugan, MD, MS, FRCP principal investigator
University of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Restrictive UFnet Rate Strategy and Liberal UFnet Rate Strategy in people with Acute Kidney Injury and Fluid Overload, run by University of Pittsburgh at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Delivered UFnet Rates. (time frame: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05306964, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2025.