Acute Kidney Injury, Critical Illness, Dialysis; Complications, Fluid Overload, Hypotension
Conditions
Keywords
Fluid overload, Acute kidney injury, Net ultrafiltration, Intensive care unit, Intradialytic hypotension, Complications, Feasibility Trial, Cardiac arrhythmias, Mortality, Dialysis dependence
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. 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.
Interventions
PROCEDURERestrictive 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.
PROCEDURELiberal 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.
Sponsors
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, two-center, unblinded, parallel-group, 2-arm, comparative effectiveness, stepped-wedge cluster-randomized trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delivered UFnet Rates. | 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. | 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 | 24 months | An enrollment rate of 1 patient per ICU per time period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Kidney Replacement Therapy | Daily from enrollment to hospital discharge or until day 28, whichever occurs first. | The number of days the patient received kidney replacement therapy while in the hospital. |
| Duration of Mechanical Ventilation | Daily from study enrollment to ICU discharge or until day 28, whichever occurs first. | The number of days the patient received mechanical ventilation while in hospital. |
| Organ Failure Free Days | Daily from study enrollment to ICU discharge or until day 28, whichever occurs first. | The no. of days the patient remained free of organ failure while in the ICU. |
| Hospital Mortality | From study enrollment to hospital discharge or day 28, whichever occurs first. | The proportion of patients who died while in the hospital. |
| 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 |
| Dependence on Kidney Replacement Therapy | From study enrollment until hospital discharge or day 28, whichever occurs first. | The proportion of patients who were on dialysis at hospital discharge. |
| ICU Length of Stay | Daily from study enrollment to ICU discharge or day 28, whichever occurs first. | The number of days patients need to stay in the ICU |
| Daily Fluid Balance (Average) | Average daily fluid balance from enrollment to ICU discharge or until day 28, whichever occurs first. | Patient daily fluid balance will be measured while on continuous kidney replacement therapy and reported as average across all study days. |
| Cumulative Fluid Balance | Daily from enrollment to ICU discharge or until day 28, whichever occurs first. | Patient cumulative fluid balance will be measured while on continuous kidney replacement therapy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| No. of Participants With Worsening of Pulmonary Edema on Chest X Ray and/or CT Scan Based on Radiologist Report. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Changes in chest X ray and CT scan will be assessed from baseline (if available). |
| No. of Participants With Worsening of Ileus on Abdominal X Ray and/or CT Scan Based on Radiologist Report. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Changes in abdominal X ray and CT scan will be assessed from baseline (if available) |
| No. of Participants With Bowel Ischemia or Anastomotic Breakdown Based on Intraoperative Findings. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Intraoperative findings of bowel ischemia or anastomotic breakdown will be noted as determined by the surgeon (if available). |
| No. of Participants With Pressure Ulceration Per Nursing Records. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | No. of participants with new diagnosis of pressure ulcerations as documented by the nursing staff in the electronic medical record (if available) |
| No. of Intradialytic Hypotension Episodes | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Intradialytic hypotension will be defined as a new mean arterial pressure \<65 mmHg, systolic blood pressure \<90 mmHg or a decline in systolic blood pressure \>40 mmHg, and/or a \>30% increase in dose of existing vasopressors, initiating a new vasopressor, or administration of fluid bolus with a goal to maintain mean arterial pressure \>=65 mmHg, systolic blood pressure \>=90 mmHg. |
| No. of Participants With New Arterial and/or Deep Vein Thrombosis as Assessed by Doppler Studies. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | New arterial thrombosis or deep vein thrombosis as assessed by doppler study (if available) |
| No. of Participants With Severe Anemia Requiring Red Cell Transfusions. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Participants with severe anemia requiring red cell transfusions (if available). |
| No. of Participants With Severe Thrombocytopenia Requiring Platelet Transfusions. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | No. of participants with severe thrombocytopenia requiring platelet transfusions (if available). |
| No. of Participants With New Secondary Infections. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | New diagnosis of secondary infections occurring after initiation of study intervention will be collected based on culture data, antibiotic use and suspected sepsis as per clinician judgment (if available). |
| No. of Participants With New Wound Infection Per Nursing Records. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | No. of participants with new diagnosis of wound infection as documented by the nursing staff in the electronic medical record (if available) |
| No. of Intradialytic Hypertension Episodes | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28. | Intradialytic hypertension will be defined as new onset systolic blood pressure \>=160 mmHg or mean arterial pressure \>=80 mmHg for more than 1 hour in the absence of any vasopressor or inotrope use. |
| No. of Episodes of Intradialytic Cardiac Arrhythmias | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | New onset intradialytic cardiac arrhythmias including supraventricular tachycardia, bradycardia, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, asystole/pulseless electrical activity will be diagnosed as per American Heart Association. |
| No. of Participants Who Receive UFnet Rates Higher Than the Assigned Intervention Arm for Treatment of Fluid Overload Emergencies. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | No. of participants in whom emergent use of UFnet rates higher than the assigned treatment arm for more than 3 consecutive hours will be noted. |
| No. of Participants With Severe Hypophosphatemia | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Hypophosphatemia defined by serum phosphate \<0.5 mg/dL |
| No. of Participants With Severe Hypokalemia | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Hypokalemia defined by serum potassium \<3.0 mg/dL |
| No. of Participants With Severe Hypocalcemia | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Hypocalcemia defined by serum calcium \<1.90 mg/dL or ionized calcium \<0.90 mmol/L |
| No. of Episodes of Stopping of CKRT System Due to Hemofilter Clotting or Clogging. | From study enrollment until termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Stopping of CKRT system due to filter clotting and/or clogging. |
| No. of Participants With Discontinuation of Fluid Removal Due to Hemodynamic Instability. | From study enrollment until termination of continuous kidney replacement therapy or day 28, whichever occurs first. | No. of participants in whom fluid removal is stopped due to hemodynamic instability such as intradialytic hypotension, cardiac arrhythmias, or cardiac arrest. |
| No. of Participants in Whom Surgical Wounds Are Left Open After Surgery Due to Tissue Edema. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | This will be determined as per the primary surgeon. Abdominal wounds left open for a second look or for abdominal re-exploration will not be counted unless there is concurrent tissue edema precluding abdominal closure. |
| No. of Participants With New Organ Dysfunction as Assessed by Change in Sequential Organ Failure Assessement (SOFA) Scoring System From Baseline. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | New organ dysfunction will be assessed by changes in SOFA scores from the baseline across the five organ systems of central nervous system, cardiovascular, respiratory, coagulation, and liver. |
| No. of Participants With Worsening of Systolic or Diastolic Cardiac Function on Echocardiogram From Baseline. | From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first. | Changes in transthoracic echocardiogram will be assessed from baseline (if available) |
Countries
United States
Participant flow
Recruitment details
RELIEVE AKI is a multicenter, prospective randomized controlled trial. This study enrolled 99 patients into the study between July 5, 2022 - June 17, 2024 at UPMC and Mayo Clinic hospitals.
Pre-assignment details
For this study, time of signing the informed consent will be the study enrollment time. There is no patient-level randomization in this trial. The randomization is at the ICU-level and based on study period of every two months.
Participants by arm
| Arm | Count |
|---|---|
| Restrictive UFnet Strategy Fluid removal will be titrated to keep net ultrafiltration rate between 0.5-1.5 mL/kg/h
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. | 41 |
| Liberal UFnet Strategy Fluid removal will be titrated to keep net ultrafiltration rate between 2.0-5.0 mL/kg/h
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. | 54 |
| Total | 95 |
Baseline characteristics
| Characteristic | Total | Restrictive UFnet Strategy | Liberal UFnet Strategy |
|---|---|---|---|
| Age, Continuous | 59 years | 63 years | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants | 39 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 86 Participants | 37 Participants | 49 Participants |
| Region of Enrollment United States | 95 Participants | 41 Participants | 54 Participants |
| Sex: Female, Male Female | 38 Participants | 15 Participants | 23 Participants |
| Sex: Female, Male Male | 57 Participants | 26 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 43 | 23 / 56 |
| other Total, other adverse events | 41 / 43 | 54 / 56 |
| serious Total, serious adverse events | 16 / 43 | 29 / 56 |
Outcome results
Primary
Delivered UFnet Rates.
A minimum separation of 0.53-0.57 mL/kg/h in mean delivered UFnet rates between the two intervention arms.
Time frame: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The primary outcome was assessed among participants assigned to the Liberal and Restrictive UFnet strategies. Even though the unit of randomization is the ICU, the outcomes were assessed only among participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Restrictive UFnet Strategy | Delivered UFnet Rates. | 1.48 mL/kg/h |
| Liberal UFnet Strategy | Delivered UFnet Rates. | 1.57 mL/kg/h |
p-value: 0.5GLMM
Primary
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.
Time frame: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The primary outcome was assessed among participants assigned to the Liberal and Restrictive UFnet strategies. Even though the unit of randomization is the ICU, the outcomes were assessed only among participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Protocol Deviation. | 4 Participants |
| Liberal UFnet Strategy | No. of Participants With Protocol Deviation. | 5 Participants |
p-value: 0.4GLMM
Primary
Participant Recruitment/ICU/ 2 Months
An enrollment rate of 1 patient per ICU per time period.
Time frame: 24 months
Population: Participant recruitment rate per ICU per 2 months during an overall recruitment period lasting 24 months across both treatment arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Restrictive UFnet Strategy | Participant Recruitment/ICU/ 2 Months | 2.33 participant/ ICU/ 2 months | Standard Deviation 2.11 |
| Liberal UFnet Strategy | Participant Recruitment/ICU/ 2 Months | 1.79 participant/ ICU/ 2 months | Standard Deviation 1.88 |
p-value: 0.5GLMM
Secondary
Cumulative Fluid Balance
Patient cumulative fluid balance will be measured while on continuous kidney replacement therapy.
Time frame: Daily from enrollment to ICU discharge or until day 28, whichever occurs first.
Population: This is the cumulative fluid balance (i.e., cumulative fluid input minus output for all days a patient was in the ICU) and was compared between the two groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Restrictive UFnet Strategy | Cumulative Fluid Balance | 229 mL |
| Liberal UFnet Strategy | Cumulative Fluid Balance | 1280.1 mL |
p-value: 0.4GLMM
Secondary
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.
Time frame: Average daily fluid balance from enrollment to ICU discharge or until day 28, whichever occurs first.
Population: The outcome measure is the average of daily fluid balance (i.e., fluid input minus output over 24 hours) while the patient stayed in the ICU and was compared between the two groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Restrictive UFnet Strategy | Daily Fluid Balance (Average) | 44 mL |
| Liberal UFnet Strategy | Daily Fluid Balance (Average) | -53 mL |
p-value: 0.3GLMM
Secondary
Dependence on Kidney Replacement Therapy
The proportion of patients who were on dialysis at hospital discharge.
Time frame: From study enrollment until hospital discharge or day 28, whichever occurs first.
Population: The secondary outcome was compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | Dependence on Kidney Replacement Therapy | 16 Participants |
| Liberal UFnet Strategy | Dependence on Kidney Replacement Therapy | 12 Participants |
p-value: 0.2GLMM
Secondary
Duration of Kidney Replacement Therapy
The number of days the patient received kidney replacement therapy while in the hospital.
Time frame: Daily from enrollment to hospital discharge or until day 28, whichever occurs first.
Population: The secondary outcome was compared among participants assigned to the two groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Restrictive UFnet Strategy | Duration of Kidney Replacement Therapy | 7 days |
| Liberal UFnet Strategy | Duration of Kidney Replacement Therapy | 5 days |
p-value: 0.5GLMM
Secondary
Duration of Mechanical Ventilation
The number of days the patient received mechanical ventilation while in hospital.
Time frame: Daily from study enrollment to ICU discharge or until day 28, whichever occurs first.
Population: The secondary outcome was compared among participants assigned to the two groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Restrictive UFnet Strategy | Duration of Mechanical Ventilation | 2 days |
| Liberal UFnet Strategy | Duration of Mechanical Ventilation | 3 days |
p-value: 0.3GLMM
Secondary
Hospital Length of Stay
The number of days patients need to stay in the hospital
Time frame: Daily from study enrollment to hospital discharge or day 28.
Population: The secondary outcome was compared among participants assigned to the two groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Restrictive UFnet Strategy | Hospital Length of Stay | 22.5 days |
| Liberal UFnet Strategy | Hospital Length of Stay | 16 days |
p-value: 0.2GLMM
Secondary
Hospital Mortality
The proportion of patients who died while in the hospital.
Time frame: From study enrollment to hospital discharge or day 28, whichever occurs first.
Population: The secondary outcome was compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | Hospital Mortality | 9 Participants |
| Liberal UFnet Strategy | Hospital Mortality | 23 Participants |
p-value: 0.02GLMM
Secondary
ICU Length of Stay
The number of days patients need to stay in the ICU
Time frame: Daily from study enrollment to ICU discharge or day 28, whichever occurs first.
Population: The secondary outcome was compared among participants assigned to the two groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Restrictive UFnet Strategy | ICU Length of Stay | 8 days |
| Liberal UFnet Strategy | ICU Length of Stay | 8 days |
p-value: 0.7GLMM
Secondary
Organ Failure Free Days
The no. of days the patient remained free of organ failure while in the ICU.
Time frame: Daily from study enrollment to ICU discharge or until day 28, whichever occurs first.
Population: The secondary outcome was compared among participants assigned to the two groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Restrictive UFnet Strategy | Organ Failure Free Days | 3.90 days | Standard Deviation 8.5 |
| Liberal UFnet Strategy | Organ Failure Free Days | 3.92 days | Standard Deviation 7.9 |
p-value: 0.3GLMM
Other Pre-specified
No. of Episodes of Intradialytic Cardiac Arrhythmias
New onset intradialytic cardiac arrhythmias including supraventricular tachycardia, bradycardia, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, asystole/pulseless electrical activity will be diagnosed as per American Heart Association.
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Restrictive UFnet Strategy | No. of Episodes of Intradialytic Cardiac Arrhythmias | 0.83 episodes per patient per day | Standard Deviation 0.29 |
| Liberal UFnet Strategy | No. of Episodes of Intradialytic Cardiac Arrhythmias | 0.92 episodes per patient per day | Standard Deviation 0.47 |
p-value: 0.2GLMM
Other Pre-specified
No. of Episodes of Stopping of CKRT System Due to Hemofilter Clotting or Clogging.
Stopping of CKRT system due to filter clotting and/or clogging.
Time frame: From study enrollment until termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Episodes of Stopping of CKRT System Due to Hemofilter Clotting or Clogging. | 34 Number of episodes |
| Liberal UFnet Strategy | No. of Episodes of Stopping of CKRT System Due to Hemofilter Clotting or Clogging. | 39 Number of episodes |
p-value: 0.8GLMM
Other Pre-specified
No. of Intradialytic Hypertension Episodes
Intradialytic hypertension will be defined as new onset systolic blood pressure \>=160 mmHg or mean arterial pressure \>=80 mmHg for more than 1 hour in the absence of any vasopressor or inotrope use.
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Restrictive UFnet Strategy | No. of Intradialytic Hypertension Episodes | 1 episodes per patient per day | Standard Deviation 0 |
| Liberal UFnet Strategy | No. of Intradialytic Hypertension Episodes | 1.05 episodes per patient per day | Standard Deviation 0.32 |
p-value: 0.1GLMM
Other Pre-specified
No. of Intradialytic Hypotension Episodes
Intradialytic hypotension will be defined as a new mean arterial pressure \<65 mmHg, systolic blood pressure \<90 mmHg or a decline in systolic blood pressure \>40 mmHg, and/or a \>30% increase in dose of existing vasopressors, initiating a new vasopressor, or administration of fluid bolus with a goal to maintain mean arterial pressure \>=65 mmHg, systolic blood pressure \>=90 mmHg.
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Restrictive UFnet Strategy | No. of Intradialytic Hypotension Episodes | 1.16 episodes per patient per day | Standard Deviation 0.34 |
| Liberal UFnet Strategy | No. of Intradialytic Hypotension Episodes | 1.20 episodes per patient per day | Standard Deviation 0.56 |
p-value: 0.7GLMM
Other Pre-specified
No. of Participants in Whom Surgical Wounds Are Left Open After Surgery Due to Tissue Edema.
This will be determined as per the primary surgeon. Abdominal wounds left open for a second look or for abdominal re-exploration will not be counted unless there is concurrent tissue edema precluding abdominal closure.
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants in Whom Surgical Wounds Are Left Open After Surgery Due to Tissue Edema. | 0 Participants |
| Liberal UFnet Strategy | No. of Participants in Whom Surgical Wounds Are Left Open After Surgery Due to Tissue Edema. | 0 Participants |
p-value: 0GLMM
Other Pre-specified
No. of Participants Who Receive UFnet Rates Higher Than the Assigned Intervention Arm for Treatment of Fluid Overload Emergencies.
No. of participants in whom emergent use of UFnet rates higher than the assigned treatment arm for more than 3 consecutive hours will be noted.
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants Who Receive UFnet Rates Higher Than the Assigned Intervention Arm for Treatment of Fluid Overload Emergencies. | 27 Participants |
| Liberal UFnet Strategy | No. of Participants Who Receive UFnet Rates Higher Than the Assigned Intervention Arm for Treatment of Fluid Overload Emergencies. | 8 Participants |
p-value: <0.001GLMM
Other Pre-specified
No. of Participants With Bowel Ischemia or Anastomotic Breakdown Based on Intraoperative Findings.
Intraoperative findings of bowel ischemia or anastomotic breakdown will be noted as determined by the surgeon (if available).
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Bowel Ischemia or Anastomotic Breakdown Based on Intraoperative Findings. | 1 Participants |
| Liberal UFnet Strategy | No. of Participants With Bowel Ischemia or Anastomotic Breakdown Based on Intraoperative Findings. | 1 Participants |
p-value: 0.9GLMM
Other Pre-specified
No. of Participants With Discontinuation of Fluid Removal Due to Hemodynamic Instability.
No. of participants in whom fluid removal is stopped due to hemodynamic instability such as intradialytic hypotension, cardiac arrhythmias, or cardiac arrest.
Time frame: From study enrollment until termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Discontinuation of Fluid Removal Due to Hemodynamic Instability. | 21 Participants |
| Liberal UFnet Strategy | No. of Participants With Discontinuation of Fluid Removal Due to Hemodynamic Instability. | 24 Participants |
p-value: 0GLMM
Other Pre-specified
No. of Participants With New Arterial and/or Deep Vein Thrombosis as Assessed by Doppler Studies.
New arterial thrombosis or deep vein thrombosis as assessed by doppler study (if available)
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With New Arterial and/or Deep Vein Thrombosis as Assessed by Doppler Studies. | 1 Participants |
| Liberal UFnet Strategy | No. of Participants With New Arterial and/or Deep Vein Thrombosis as Assessed by Doppler Studies. | 1 Participants |
p-value: 0GLMM
Other Pre-specified
No. of Participants With New Organ Dysfunction as Assessed by Change in Sequential Organ Failure Assessement (SOFA) Scoring System From Baseline.
New organ dysfunction will be assessed by changes in SOFA scores from the baseline across the five organ systems of central nervous system, cardiovascular, respiratory, coagulation, and liver.
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With New Organ Dysfunction as Assessed by Change in Sequential Organ Failure Assessement (SOFA) Scoring System From Baseline. | 19 Participants |
| Liberal UFnet Strategy | No. of Participants With New Organ Dysfunction as Assessed by Change in Sequential Organ Failure Assessement (SOFA) Scoring System From Baseline. | 33 Participants |
p-value: 0.2GLMM
Other Pre-specified
No. of Participants With New Secondary Infections.
New diagnosis of secondary infections occurring after initiation of study intervention will be collected based on culture data, antibiotic use and suspected sepsis as per clinician judgment (if available).
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With New Secondary Infections. | 3 Participants |
| Liberal UFnet Strategy | No. of Participants With New Secondary Infections. | 4 Participants |
p-value: 0.3GLMM
Other Pre-specified
No. of Participants With New Wound Infection Per Nursing Records.
No. of participants with new diagnosis of wound infection as documented by the nursing staff in the electronic medical record (if available)
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With New Wound Infection Per Nursing Records. | 0 Participants |
| Liberal UFnet Strategy | No. of Participants With New Wound Infection Per Nursing Records. | 1 Participants |
p-value: 0GLMM
Other Pre-specified
No. of Participants With Pressure Ulceration Per Nursing Records.
No. of participants with new diagnosis of pressure ulcerations as documented by the nursing staff in the electronic medical record (if available)
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Pressure Ulceration Per Nursing Records. | 1 Participants |
| Liberal UFnet Strategy | No. of Participants With Pressure Ulceration Per Nursing Records. | 0 Participants |
p-value: 0GLMM
Other Pre-specified
No. of Participants With Severe Anemia Requiring Red Cell Transfusions.
Participants with severe anemia requiring red cell transfusions (if available).
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Severe Anemia Requiring Red Cell Transfusions. | 16 Participants |
| Liberal UFnet Strategy | No. of Participants With Severe Anemia Requiring Red Cell Transfusions. | 26 Participants |
p-value: 0.5GLMM
Other Pre-specified
No. of Participants With Severe Hypocalcemia
Hypocalcemia defined by serum calcium \<1.90 mg/dL or ionized calcium \<0.90 mmol/L
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Severe Hypocalcemia | 1 Participants |
| Liberal UFnet Strategy | No. of Participants With Severe Hypocalcemia | 1 Participants |
p-value: 0.9GLMM
Other Pre-specified
No. of Participants With Severe Hypokalemia
Hypokalemia defined by serum potassium \<3.0 mg/dL
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Severe Hypokalemia | 1 Participants |
| Liberal UFnet Strategy | No. of Participants With Severe Hypokalemia | 0 Participants |
p-value: 0.5GLMM
Other Pre-specified
No. of Participants With Severe Hypophosphatemia
Hypophosphatemia defined by serum phosphate \<0.5 mg/dL
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Severe Hypophosphatemia | 0 Participants |
| Liberal UFnet Strategy | No. of Participants With Severe Hypophosphatemia | 0 Participants |
p-value: 0GLMM
Other Pre-specified
No. of Participants With Severe Thrombocytopenia Requiring Platelet Transfusions.
No. of participants with severe thrombocytopenia requiring platelet transfusions (if available).
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Severe Thrombocytopenia Requiring Platelet Transfusions. | 6 Participants |
| Liberal UFnet Strategy | No. of Participants With Severe Thrombocytopenia Requiring Platelet Transfusions. | 15 Participants |
p-value: 0.2GLMM
Other Pre-specified
No. of Participants With Worsening of Ileus on Abdominal X Ray and/or CT Scan Based on Radiologist Report.
Changes in abdominal X ray and CT scan will be assessed from baseline (if available)
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Worsening of Ileus on Abdominal X Ray and/or CT Scan Based on Radiologist Report. | 0 Participants |
| Liberal UFnet Strategy | No. of Participants With Worsening of Ileus on Abdominal X Ray and/or CT Scan Based on Radiologist Report. | 0 Participants |
p-value: 0GLMM
Other Pre-specified
No. of Participants With Worsening of Pulmonary Edema on Chest X Ray and/or CT Scan Based on Radiologist Report.
Changes in chest X ray and CT scan will be assessed from baseline (if available).
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Worsening of Pulmonary Edema on Chest X Ray and/or CT Scan Based on Radiologist Report. | 4 Participants |
| Liberal UFnet Strategy | No. of Participants With Worsening of Pulmonary Edema on Chest X Ray and/or CT Scan Based on Radiologist Report. | 6 Participants |
p-value: 0.9GLMM
Other Pre-specified
No. of Participants With Worsening of Systolic or Diastolic Cardiac Function on Echocardiogram From Baseline.
Changes in transthoracic echocardiogram will be assessed from baseline (if available)
Time frame: From study enrollment until 24 hours after termination of continuous kidney replacement therapy or day 28, whichever occurs first.
Population: The adverse events were compared among participants assigned to the two groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restrictive UFnet Strategy | No. of Participants With Worsening of Systolic or Diastolic Cardiac Function on Echocardiogram From Baseline. | 0 Participants |
| Liberal UFnet Strategy | No. of Participants With Worsening of Systolic or Diastolic Cardiac Function on Echocardiogram From Baseline. | 0 Participants |
p-value: 0GLMM