Since the primary feasibility found outcome was based on the dose of CRRT received, patients for whom dose could not be readily calculated (those who received no RRT or forms of RRT other than CRRT) were excluded from the analysis related to feasibility. However, clinical outcomes are reported for all randomized participants.Descriptive statistics were used to characterize participants in either arm. Continuous variables are presented as means (SD) or medians (interquartile range, IQR) and two-group comparisons were performed with the t-test or Wilcoxon test, as appropriate. Two-group comparisons involving categorical variables were carried out with the chi square test. Analysis of covariance, adjusted for baseline SOFA score, was used to evaluate the change in SOFA score on days 1 and 2.

Linear mixed models adjusted for baseline SOFA score and day of study therapy were used to evaluate the impact of RRT mode on SOFA score over the first week of therapy. For the fixed effect of treatment (that is, CVVH vs. CVVHD) 95% confidence intervals (CI) were obtained by profiling the log-likelihood function. All analyses were performed using R version 2.12.0 (R Development Core Team 2010, Vienna, Austria).ResultsWe screened 347 patients; 143 were eligible for participation and 79 individuals (55.2%) were enrolled over a 24-month time period. The inability to obtain consent from the patient or SDM was the reason for the non-enrollment of otherwise eligible patients. One patient was excluded shortly after enrollment after it was decided to pursue a non-continuous form of RRT.

In total, 78 patients were randomized (39 to CVVH, and 39 to CVVHD). In one case, prior to the start of therapy it was recognized that a patient randomized to CVVHD was inappropriately enrolled as the indication for RRT was toxin removal rather than AKI per se. This patient was excluded from all further analyses. Clinical outcomes are reported in an intention-to-treat fashion for the remaining 77 patients (CVVH, 39; CVVHD, 38). Four patients randomized to CVVH were excluded from the feasibility analysis, two due to death prior to commencement of study RRT, and two due to receipt of continuous venovenous hemodiafiltration as the initial mode of therapy. The indication(s) for RRT was (were) oliguria, metabolic acidosis, hyperkalemia and uremia in 34, 17, 6 and 8 patients, respectively, in the CVVH arm. In the CVVHD arm, these indications guided the inclusion of 36, 15, 4 and 3 participants, respectively. In total, 73 participants commenced the therapy to which they were randomized (CVVH, 35; CVVHD, 38); these individuals contributed to the analysis relating to the feasibility of treatment delivery (Figure (Figure11).Figure 1Flow of patients through Cilengitide the trial.