A Multi-Center, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients with Acute Kidney Injury

James A Tumlin, Claude M Galphin, Ashita J Tolwani, Micah R Chan, Anitha Vijayan, Kevin Finkel, Balazs Szamosfalvi, Devasmita Dev, J Ricardo DaSilva, Brad C Astor, Alexander S Yevzlin, H David Humes, SCD Investigator Group, Luis Juncos, Sevag Demirjian, Jorge Cerda, Ravindra Mehta, Jiuming Ye, Winfred Williams Jr, Cybele Ghossein, Bartley Griffith, Edward Ross, Ashwani Gupta, Anna Vinnikova, Robert Brown, Juan Carlos Velez, James A Tumlin, Claude M Galphin, Ashita J Tolwani, Micah R Chan, Anitha Vijayan, Kevin Finkel, Balazs Szamosfalvi, Devasmita Dev, J Ricardo DaSilva, Brad C Astor, Alexander S Yevzlin, H David Humes, SCD Investigator Group, Luis Juncos, Sevag Demirjian, Jorge Cerda, Ravindra Mehta, Jiuming Ye, Winfred Williams Jr, Cybele Ghossein, Bartley Griffith, Edward Ross, Ashwani Gupta, Anna Vinnikova, Robert Brown, Juan Carlos Velez

Abstract

Objective: Acute kidney injury (AKI) is a highly morbid condition in critically ill patients that is associated with high mortality. Previous clinical studies have demonstrated the safety and efficacy of the Selective Cytopheretic Device (SCD) in the treatment of AKI requiring continuous renal replacement therapy in the intensive care unit (ICU).

Design, setting, patients: A randomized, controlled trial of 134 ICU patients with AKI, 69 received continuous renal replacement therapy (CRRT) alone and 65 received SCD therapy.

Results: No significant difference in 60-day mortality was observed between the treated (27/69; 39%) and control patients (21/59; 36%, with six patients lost to follow up) in the intention to treat (ITT) analysis. Of the 19 SCD subjects (CRRT+SCD) and 31 control subjects (CRRT alone) who maintained a post-filter ionized calcium (iCa) level in the protocol's recommended range (≤ 0.4 mmol/L) for greater or equal to 90% of the therapy time, 60-day mortality was 16% (3/19) in the SCD group compared to 41% (11/27) in the CRRT alone group (p = 0.11). Dialysis dependency showed a borderline statistically significant difference between the SCD treated versus control CRRT alone patients maintained for ≥ 90% of the treatment in the protocol's recommended (r) iCa target range of ≤ 0.4 mmol/L with values of, 0% (0/16) and 25% (4/16), respectively (P = 0.10). When the riCa treated and control subgroups were compared for a composite index of 60 day mortality and dialysis dependency, the percentage of SCD treated subjects was 16% versus 58% in the control subjects (p<0.01). The incidence of serious adverse events did not differ between the treated (45/69; 65%) and control groups (40/65; 63%; p = 0·86).

Conclusion: SCD therapy may improve mortality and reduce dialysis dependency in a tightly controlled regional hypocalcaemic environment in the perfusion circuit.

Trial registration: ClinicalTrials.gov NCT01400893 https://ichgcp.net/clinical-trials-registry/NCT01400893.

Conflict of interest statement

Competing Interests: The authors received funding from CytoPherx, Inc, a commercial company, in the form of stock options and salaries for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Flow chart of the disposition…
Fig 1. Flow chart of the disposition in all of the patients (N = 134) enrolled.
For the purpose of statistical analysis ITT is defined as all control and all treatment, whereas mITT is defined as all control and all treatment with iCa at recommended range >90% of the time.

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