Clinical trial NCT00675818: The Optimal Mode of Renal Replacement Therapy in Acute Kidney Injury (OMAKI) Study
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Kidney Injury
Keywords: acute kidney injury
renal replacement therapy
critical care unit
hemodialysis
hemofiltration
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: University of Toronto
First posted: 2008-05-12
Enrollment: 78
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Adult patients (over 16 years of age) admitted to a participating ICU
2. Serum creatinine increase of ≥ 50% from baseline
3. Hemodynamic instability as defined by the cardiovascular component of the SOFA score of ≥ 1
4. Attending physician deems the patient a candidate for RRT for at least one of the following reasons:

   1. Presence of oliguria, defined as a urine output of \< 100 mL in the preceding 4 hours
   2. metabolic acidosis (HCO3- \< 15 mmol/L and pH \< 7.25)
   3. refractory hyperkalemia (K \> 6.0 mmol/L)
   4. azotemia (BUN \> 50 mmol/L)
   5. suspected uremic organ involvement (pericarditis, encephalopathy, neuropathy or myopathy)

Exclusion Criteria:

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

Primary outcomes:
measure: 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.
timeFrame: 60 days
Secondary outcomes:
measure: Change in Sequential Organ Failure Assessment (SOFA) score.
timeFrame: 7 days
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mt. Sinai Hospital
state: Ontario
Study officials:
affiliation: St. Michael's Hospital and University of Toronto
name: Ron Wald, MDCM
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Wald R, Friedrich JO, Bagshaw SM, Burns KE, Garg AX, Hladunewich MA, House AA, Lapinsky S, Klein D, Pannu NI, Pope K, Richardson RM, Thorpe K, Adhikari NK. Optimal Mode of clearance in critically ill patients with Acute Kidney Injury (OMAKI)--a pilot randomized controlled trial of hemofiltration versus hemodialysis: a Canadian Critical Care Trials Group project. Crit Care. 2012 Oct 24;16(5):R205. doi: 10.1186/cc11835.