Acute Renal Failure
Conditions
Keywords
CVVHDF Dose Study
Brief summary
In the last three decades, the mortality associated with acute renal failure (ARF) in the ICU has remained unchanged at greater than 50%, despite improvements in dialysis technology. The primary objective is to determine whether Continuous Veno-Venous Hemodiafiltration (CVVHDF) using an ultrafiltration rate of 35 ml/hr/kg (high dose) leads to a greater reduction in all-cause ICU mortality compared to standard CVVHDF using an ultrafiltration rate of 20 ml/hr/kg.
Detailed description
Although the worldwide standard for renal replacement therapy is intermittent hemodialysis(IHD), continuous renal replacement therapy (CRRT) has emerged as an alternative form of renal replacement therapy in the critical care setting due to its advantages of slow continuous fluid removal, steady acid-base correction, and hemodynamic stability. There are no standard protocols for initiating or administering CRRT, and practice patterns vary widely among institutions, with less than 25% of patients with ARF in the ICU receiving this therapy in the United States. Various CRRT modalities are available that use diffusion, convection, or a combination of both to obtain adequate solute clearance. However, there is no consensus as to the optimal dialysis modality, adequate dialysis dose, or optimal clearance modality (convection vs. diffusion). Clinical trials are needed to determine the optimal method of administering CRRT, with respect to modality, dose of dialysis, and time of initiation of therapy. Although some studies suggest that a higher dose of dialysis improves survival, there have been no prospective randomized studies comparing the effectiveness of diffusion and convection, combined together, for solute clearance.
Interventions
DEVICEStandard dose of dialysis
Continuous Venovenous Hemodiafiltration (CVVHDF) effluent dose of 20 ml/kg/hr
DEVICEHigh dose of dialysis
Continuous Venovenous Hemodiafiltration (CVVHDF) effluent rate 35 ml/kg/hr
Sponsors
Pfizer
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female \> or equal to 19 yrs of age * ARF defined by at least one of the following: * Volume overload from inadequate urine output despite diuretic agents. * Oliguria (urine output \< 200 ml/12hrs) despite fluid resuscitation and diuretic administration. * Anuria (urine output \< 50 ml/12 hrs). * Acute azotemia (BUN \> or equal to 80 mg/dl). * Acute hyperkalemia not responsive to medication (K+ \> or equal to 6.5mmol/L) * An increase in serum creatinine of \> 2.5 mg/dl from normal values or a sustained rise in serum creatinine of \> or equal to 1 mg/dl over baseline.
Exclusion criteria
* Patients with end stage renal disease * Patients who have had more than one previous dialysis session for acute or chronic renal failure during the current hospitalization * Patient weight greater than 125 kg * Patient weight less than 50 kg * Pregnancy * Prisoner * Non-candidacy for continuous renal replacement therapy (CRRT) * Patient/surrogate refusal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Alive at 30 Days After Enrollment Compared Between High Dose Versus Standard Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | Up to 30 days | The primary objective is to determine whether Continuous Venovenous Hemodiafiltration (CVVHDF) using an effluent rate of 35 ml/hr/kg (high dose) leads to an increased participant survival time as compared to CVVHDF using the standard effluent rate of 25 ml/hr/kg as measured by days on continuous renal replacement therapy (CRRT) at enrollment up to 30 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recovery of Renal Function, Defined as Not Requiring Dialysis After Discontinuation of CRRT | Up to 30 days | The number of participants who recover renal function at 30 days after enrollment in each arm. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Dose Continuous Venovenous Hemodiafiltration (CVVHDF) Standard dose Continuous Venovenous Hemodiafiltration (CVVHDF) at an effluent rate of 20 ml/kg/hr | 100 |
| High Dose Continuous Venovenous Hemodiafiltration (CVVHDF) High dose Continuous Venovenous Hemodiafiltration (CVVHDF) at an effluent rate of 35 ml/kg/hr | 100 |
| Total | 200 |
Baseline characteristics
| Characteristic | High Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | Standard Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 36 Participants | 43 Participants | 79 Participants |
| Age, Categorical Between 18 and 65 years | 64 Participants | 57 Participants | 121 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 16 | 62 years STANDARD_DEVIATION 15 | 60 years STANDARD_DEVIATION 15 |
| Region of Enrollment United States | 100 participants | 100 participants | 200 participants |
| Sex: Female, Male Female | 41 Participants | 43 Participants | 84 Participants |
| Sex: Female, Male Male | 59 Participants | 57 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 100 | 0 / 100 |
| serious Total, serious adverse events | 63 / 100 | 72 / 100 |
Outcome results
Primary
Number of Participants Alive at 30 Days After Enrollment Compared Between High Dose Versus Standard Dose Continuous Venovenous Hemodiafiltration (CVVHDF)
The primary objective is to determine whether Continuous Venovenous Hemodiafiltration (CVVHDF) using an effluent rate of 35 ml/hr/kg (high dose) leads to an increased participant survival time as compared to CVVHDF using the standard effluent rate of 25 ml/hr/kg as measured by days on continuous renal replacement therapy (CRRT) at enrollment up to 30 days.
Time frame: Up to 30 days
Population: Intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | Number of Participants Alive at 30 Days After Enrollment Compared Between High Dose Versus Standard Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | 56 participants |
| High Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | Number of Participants Alive at 30 Days After Enrollment Compared Between High Dose Versus Standard Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | 49 participants |
Secondary
Recovery of Renal Function, Defined as Not Requiring Dialysis After Discontinuation of CRRT
The number of participants who recover renal function at 30 days after enrollment in each arm.
Time frame: Up to 30 days
Population: intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | Recovery of Renal Function, Defined as Not Requiring Dialysis After Discontinuation of CRRT | 37 Participants |
| High Dose Continuous Venovenous Hemodiafiltration (CVVHDF) | Recovery of Renal Function, Defined as Not Requiring Dialysis After Discontinuation of CRRT | 28 Participants |