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

Not Applicable

Completed

• Conditions: Acute Kidney Injury; Fluid Overload; Hypotension; Dialysis; Complications; Critical Illness
• Interventions: Procedure: Restrictive UFnet Rate Strategy; Procedure: Liberal UFnet Rate Strategy

• Registration Number: NCT05306964
• Lead Sponsor: University of Pittsburgh

Brief 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. 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.

Study Timeline

• Study First Submitted: 2022-03-02
• Study First Submitted QC: 2022-03-22
• Study First Posted: 2022-04-01
• Study Start: 2022-07-05
• Primary Completion: 2024-06-17
• Study Completion: 2024-06-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-11
• Last Update Posted: 2024-07-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Restrictive UFnet Strategy	Restrictive UFnet Rate Strategy	Fluid removal will be titrated to keep net ultrafiltration rate between 0.5-1.5 mL/kg/h
Liberal UFnet Strategy	Liberal UFnet Rate Strategy	Fluid removal will be titrated to keep net ultrafiltration rate between 2.0-5.0 mL/kg/h

Primary Outcome Measures

Name	Time	Method
Delivered UFnet rates.	Until the end of continuous kidney replacement therapy or day 28.	A minimum separation of 0.53-0.57 mL/kg/h in mean delivered UFnet rates between the two intervention arms.
Participant recruitment rate over 21 months	Through study completion, an average of 21 months	An enrollment rate of 1 patient per ICU per time window.
No. of participants with protocol deviation.	Until the end of continuous kidney replacement therapy or day 28.	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.

Secondary Outcome Measures

Name	Time	Method
Hospital length of stay	Daily from study enrollment to hospital discharge or day 28.	The number of days patients need to stay in the hospital
Duration of mechanical ventilation	Daily from study enrollment to ICU discharge or until day 28.	The number of days the patient received mechanical ventilation while in hospital.
ICU length of stay	Daily from study enrollment to ICU discharge or day 28.	The number of days patients need to stay in the ICU
Cumulative fluid balance	Daily from enrollment to ICU discharge or until day 28.	Patient cumulative fluid balance will be measured while on continuous kidney replacement therapy.
Duration of kidney replacement therapy	Daily from enrollment to hospital discharge or until day 28.	The number of days the patient received kidney replacement therapy while in the hospital.
Dependence on kidney replacement therapy	From study enrollment until hospital discharge or day 28.	The proportion of patients who were on dialysis at hospital discharge.
Hospital mortality	From study enrollment to hospital discharge or day 28.	The proportion of patients who died while in the hospital.
Daily fluid balance	Daily from enrollment to ICU discharge or until day 28.	Patient daily fluid balance will be measured while on continuous kidney replacement therapy.
Organ failure free days	Daily from study enrollment to ICU discharge or until day 28.	The no. of days the patient remained free of organ failure while in the ICU.

Trial Locations

Locations (2)

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States