The Optimal Mode of Renal Replacement Therapy in Acute Kidney Injury (OMAKI) Study

Sponsor

Unity Health Toronto (Other)

Overall Status

Completed

CT.gov ID

NCT00675818

Collaborator

University of Toronto (Other)

Enrollment

Locations

Arms

Duration (Months)

15.6

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Acute kidney injury (AKI) in the intensive care unit is common, devastating and costly. However, minimal evidence exists to guide the prescription of optimal renal replacement therapy (RRT). An important area of uncertainty surrounds the relative effects of convective versus diffusive modes of clearance. Although both clearance modes provide similar degrees of small molecule clearance, convective modes permit the enhanced clearance of larger-sized molecules which may mediate kidney and systemic toxicity in the setting of AKI.

Continuous renal replacement therapies (CRRTs) are frequently applied in critically ill patients with AKI. Convective clearance, as applied through continuous venovenous hemofiltration (CVVH) and diffusive clearance, as applied through continuous venovenous hemodialysis (CVVHD), may be readily compared in the context of patients receiving CRRT.

The purpose of this study is to examine the feasibility of conducting a larger study that will determine whether convective clearance (hemofiltration) confers improved outcomes as compared to diffusive clearance (hemodialysis) in patients with AKI.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Device: Continuous venvenous hemofiltration (CVVH) Device: Continuous venovenous hemodialysis (CVVHD)	Phase 4

Detailed Description

The optimal mode of clearance in critically ill patients with acute kidney injury (AKI) who require renal replacement therapy (RRT) is unclear. Although both convection (as provided by hemofiltration) and diffusion (as provided by hemodialysis) provide equivalent removal of small-sized molecules, hemofiltration offers the potential for removal of large molecules many of which may be toxic. Hemofiltration and hemodialysis have never been compared in a rigorous randomized trial to date.

Continuous renal replacement therapies (CRRT) are widely used in the management of critically ill patients with AKI and current CRRT technology provides a practical platform on which to compare convective and diffusive clearance. We hypothesize that continuous venovenous hemofiltration (CVVH)- at identical doses of small molecule clearance that are provided by the comparison treatment of continuous venovenous hemodialysis (CVVHD)- leads to improved patient outcomes.

This study is an unblinded pilot RCT designed to test the feasibility of conducting a subsequent large scale study that will assess whether CVVH leads to improved patient outcomes (ie, survival, renal recovery) as compared to CVVHD. Although we will be collecting the full array of patient-relevant data for up to 60 days following randomization, the main purpose of this pilot study is to demonstrate the feasibility of recruiting, treating and following patients for a study designed to test this hypothesis.

Patient Population

The recruitment target for this study is 75 patients.

The inclusion and exclusion criteria are designed to enroll patients with AKI on the basis of presumed acute tubular necrosis who would ordinarily be candidates for continuous renal replacement therapies (CRRT) in Canada. The overall philosophy is to enroll and begin applying the study therapy as close as possible to the clinical need to start renal replacement therapy. Similarly, we would like to avoid enrolling patients whose risk of death is so high that the study therapy is unlikely to impact on the clinical outcome.

Treatments

We will employ equivalent doses of hemofiltration (35 mL/kg/hr of replacement fluid) and hemodialysis (35 mL/kg/hr of dialysate).

Therapies will be administered using Primsaflex machines (Gambro Inc.) using regional citrate anticoagulation, heparin anticoagulation or no anticoagulation. Hospital-specific protocols for anticoagulation will be used. We have obtained Health Canada permission to utilize Prismocal, Normocarb, Hemosol BO and Prismasol 4 as infusates in patients receiving CVVH.

Study Design

Study Type:

Interventional

Actual Enrollment :

78 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Optimal Mode of Renal Replacement Therapy in Acute Kidney Injury (OMAKI) Study: A Pilot Randomized Controlled Trial of Convective Versus Diffusive Clearance

Study Start Date :

May 1, 2008

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 CVVH: Patients in this arm will receive CVVH at a replacement fluid rate of 35 mL/kg/h.	Device: Continuous venvenous hemofiltration (CVVH) Continuous venovenous hemofiltration with a replacement fluid rate of 35 mL/kg/hr.
Active Comparator: 2 CVVHD: Patients in this arm will receive CVVHD at a dialysate flow rate of 35 mL/kg/h.	Device: Continuous venovenous hemodialysis (CVVHD) Continuous venovenous hemodialysis at a dialysate flow rate of 35 mL/kg/hr.

Arm

Intervention/Treatment

Experimental: 1

CVVH: Patients in this arm will receive CVVH at a replacement fluid rate of 35 mL/kg/h.

Device: Continuous venvenous hemofiltration (CVVH)

Continuous venovenous hemofiltration with a replacement fluid rate of 35 mL/kg/hr.

Active Comparator: 2

CVVHD: Patients in this arm will receive CVVHD at a dialysate flow rate of 35 mL/kg/h.

Device: Continuous venovenous hemodialysis (CVVHD)

Continuous venovenous hemodialysis at a dialysate flow rate of 35 mL/kg/hr.

Outcome Measures

Primary Outcome Measures

We will study the feasibility of recruiting ther target population, administering the study therapies according to pre-defined protocols and following patients for clinical endpoints. [60 days]

Secondary Outcome Measures

Change in Sequential Organ Failure Assessment (SOFA) score. [7 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients (over 16 years of age) admitted to a participating ICU
Serum creatinine increase of ≥ 50% from baseline
Hemodynamic instability as defined by the cardiovascular component of the SOFA score of ≥ 1
Attending physician deems the patient a candidate for RRT for at least one of the following reasons:
Presence of oliguria, defined as a urine output of < 100 mL in the preceding 4 hours
metabolic acidosis (HCO3- < 15 mmol/L and pH < 7.25)
refractory hyperkalemia (K > 6.0 mmol/L)
azotemia (BUN > 50 mmol/L)
suspected uremic organ involvement (pericarditis, encephalopathy, neuropathy or myopathy)

Exclusion Criteria:

renal replacement therapy within the previous 2 months
presence of renal obstruction
receipt of a kidney transplant in the previous year
diagnosis of rapidly progressive glomerulonephritis, vasculitis, or acute interstitial nephritis
indication for intermittent hemodialysis, specifically severe hyperkalemia, dialyzable drug or toxin
terminal illness with associated life expectancy less than 2 months
patients who are moribund
prior enrollment in this study
enrollment in a competing ICU interventional study
no CRRT machine available
acute renal replacement ongoing for > 36 hours

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alberta	Edmonton	Alberta	Canada
2	London Health Sciences Centre	London	Ontario	Canada
3	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
4	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
5	Mt. Sinai Hospital	Toronto	Ontario	Canada	M5G 1X5