High Dose CVVHDF Compared to Standard Dose CVVHDF (CVVHDF)

A Randomized Prospective Study Comparing High Dose Continuous Venovenous Hemodiafiltration (CVVHDF) to Standard Dose CVVHDF in Critically Ill Patients With Acute Renal Failure at the University of Alabama at Birmingham

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.

Study Overview

• Status: Completed
• Conditions: Acute Renal Failure
• Intervention / Treatment: Device: Standard dose of dialysis; Device: High dose of dialysis

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Standard dose Continuous Venovenous Hemodiafiltration (CVVHDF) at an effluent rate of 20 ml/kg/hr	Device: Standard dose of dialysis; Continuous Venovenous Hemodiafiltration (CVVHDF) effluent dose of 20 ml/kg/hr
Experimental: 2; High dose Continuous Venovenous Hemodiafiltration (CVVHDF) at an effluent rate of 35 ml/kg/hr	Device: High dose of dialysis; Continuous Venovenous Hemodiafiltration (CVVHDF) effluent rate 35 ml/kg/hr

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 30 days

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Pfizer
• Investigators: Principal Investigator: Ashita J. Tolwani, MD, The University of Alabama at Birmingham, Division of Nephrology

Publications and helpful links

General Publications

• Tsujimoto Y, Miki S, Shimada H, Tsujimoto H, Yasuda H, Kataoka Y, Fujii T. Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: November 19, 2007
• First Submitted That Met QC Criteria: November 20, 2007
• First Posted (Estimate): November 21, 2007

Study Record Updates

• Last Update Posted (Estimate): April 14, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: CVVHDF Dose Study
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: X030108004