After this protocol change, twenty patients were enrolled in the trial; the 4,000 mL/hr dosing cap was invoked in six participants (five allocated to CVVHD and one to CVVH) who would have otherwise needed higher flows to achieve an actual total dose of 35 mL/kg/hr.All study therapies were delivered by the Gambro Prismaflex? RRT machine using the ST100 (surface area 1.0 m2) or ST150 (surface www.selleckchem.com/products/MLN8237.html area 1.5 m2) filter sets, which contain a polyacrylonitrile AN69 membrane (Gambro, Richmond Hill, ON, Canada). We permitted the use of any commercially available dialysate and replacement solutions. Decisions regarding circuit anticoagulation (heparin, regional citrate anticoagulation, or no anticoagulation) and volume control were at the discretion of the attending physicians.

Patients remained on study therapy until death, withdrawal of CRRT as part of withdrawal of life support, hemodynamic stability (SOFA-cardiovascular score < 2 for > 24 hrs) permitting stepdown to intermittent hemodialysis, or recovery of kidney function (defined as urine output > 500 mL in the preceding 12 hrs, and most recent serum potassium < 5.5 mmol/L and serum bicarbonate > 18 mmol/L).OutcomesThe primary feasibility outcome of this study was the ability to administer > 75% of the prescribed CRRT dose to participants in each treatment arm. Secondary feasibility outcomes included the ability to enroll > 25% of fully eligible patients and the ability to follow > 95% of patients to 60 days following randomization (the anticipated follow-up period for the future definitive principal study).

Secondary outcomes included change in SOFA score from baseline to days 1, 2 and 7, respectively, following randomization. Serial changes in SOFA scores have been shown to be correlated with clinical outcomes in critically ill patients with AKI who require RRT [11].Data collectionTrained research coordinators collected baseline clinical and demographic data, and information on pre-existing medical conditions. Specific risk factors for AKI were ascertained, including recent procedures, nephrotoxins, and sepsis (defined using consensus guidelines [12]). SOFA score was calculated at the time of randomization and on each day of study therapy. The SOFA-Cardiovascular score was modified to include the receipt of vasopressin. Patients receiving RRT on a given day were assigned a SOFA-Renal score of 4, regardless of urine output or serum creatinine.

Participants were followed until death or a maximum of 60 days from randomization, at which time vital status and the ongoing need for RRT among survivors were recorded.Statistical analysesAs this was a feasibility trial with the primary objective of informing Carfilzomib the design of a large-scale RCT, we planned to enroll a convenience sample of 75 participants from six sites.