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,Micah R Chan,H David Humes,Devasmita Dev,Claude M Galphin,J Ricardo Dasilva,Kevin Finkel,Anitha Vijayan,Brad C Astor,Balazs Szamosfalvi,Ashita J Tolwani,Scd Investigator Group ,Alexander S Yevzlin

doi:10.1371/journal.pone.0132482

Abstract

ObjectiveAcute 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, PatientsA randomized, controlled trial of 134 ICU patients with AKI, 69 received continuous renal replacement therapy (CRRT) alone and 65 received SCD therapy.ResultsNo 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 (≤ 0.4mmol/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).ConclusionSCD therapy may improve mortality and reduce dialysis dependency in a tightly controlled regional hypocalcaemic environment in the perfusion circuit.Trial RegistrationClinicalTrials.gov NCT01400893 http://clinicaltrials.gov/ct2/show/NCT01400893

Highlights

Acute kidney injury (AKI) is a highly morbid condition in critically ill patients with mortality rates exceeding 50% [1,2,3,4,5]
AKI promotes a systemic inflammatory response syndrome (SIRS) which results in systemic microvascular damage and, if severe, multi-organ dysfunction [6, 7]
A selective cytopheretic device, which immunomodulates activated circulating leukocytes in the presence of a citrate induced hypocalcemic environment within an extracorporeal blood circuit, including neutrophils and monocytes was compared to standard of care therapy with continuous renal replacement therapy (CRRT) alone

Summary

Introduction

Acute kidney injury (AKI) is a highly morbid condition in critically ill patients with mortality rates exceeding 50% [1,2,3,4,5]. AKI promotes a systemic inflammatory response syndrome (SIRS) which results in systemic microvascular damage and, if severe, multi-organ dysfunction [6, 7]. Leukocytes, especially neutrophils, are major contributors to the pathogenesis and progression of many inflammatory disorders, including SIRS, sepsis, ischemia reperfusion injury, and acute respiratory distress syndrome (ARDS). Many therapeutic approaches are under investigation to limit the activation and tissue accumulation of leukocytes at sites of inflammation to minimize tissue destruction and disease progression [9,10,11]

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Conclusion