@article{e3c2828f317a4026b9d50b56dcfb54df,
title = "Use of the Selective Cytopheretic Device in Critically Ill Children",
abstract = "Introduction: Critically ill children with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect when circuit ionized calcium (iCa2+) is maintained at <0.40 mmol/l with regional citrate anticoagulation (RCA). In a randomized trial of adult patients on CRRT, those treated with the SCD maintaining an iCa2+ <0.40 mmol/l had improved survival/dialysis independence. We conducted a US Food and Drug Administration (FDA)–sponsored study to evaluate safety and feasibility of the SCD in 16 critically ill children. Methods: Four pediatric intensive care units (ICUs) enrolled children with AKI and multiorgan dysfunction receiving CKRT to receive the SCD integrated post-CKRT membrane. RCA was used to achieve a circuit iCa2+ level <0.40 mmol/l. Subjects received SCD treatment for 7 days or CKRT discontinuation, whichever came first. Results: The FDA target enrollment of 16 subjects completed the study from December 2016 to February 2020. Mean age was 12.3 ± 5.1 years, weight was 53.8 ± 28.9 kg, and median Pediatric Risk of Mortality II was 7 (range 2–19). Circuit iCa2+ levels were maintained at <0.40 mmol/l for 90.2% of the SCD therapy time. Median SCD duration was 6 days. Fifteen subjects survived SCD therapy; 12 survived to ICU discharge. All ICU survivors were dialysis independent at 60 days. No SCD-related adverse events (AEs) were reported. Conclusion: Our data demonstrate that SCD therapy is feasible and safe in children who require CKRT. Although we cannot make efficacy claims, the 75% survival rate and 100% renal recovery rate observed suggest a possible favorable benefit-to-risk ratio.",
keywords = "acute kidney injury, children, continuous kidney replacement therapy, selective cytopheretic device",
author = "Goldstein, {Stuart L.} and Askenazi, {David J.} and Basu, {Rajit K.} and Selewski, {David T.} and Paden, {Matthew L.} and Krallman, {Kelli A.} and Kirby, {Cassie L.} and Mottes, {Theresa A.} and Tara Terrell and Humes, {H. David}",
note = "Funding Information: We conducted this prospective study at 4 US centers (Cincinnati Children's Hospital Medical Center, University of Michigan / CS Mott Children's Hospital, University of Alabama at Birmingham / Children's of Alabama, and Emory University / Children's Healthcare of Atlanta at Egleston). Children of 15 kg or more in weight, up to 22 years of age, who were admitted to an ICU were screened for eligibility. Subjects who had AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria,29 and MOD and were receiving CKRT as part of the standard of clinical care were eligible to be enrolled in the study. MOD was defined as respiratory disease requiring invasive mechanical ventilation and/or cardiovascular compromise requiring the provision of a continuous infusion of an inotropic/vasoactive medication. These criteria have been repeatedly shown to be associated with AKI development and mortality in critically ill children. 30–32 Subject severity of illness was assessed by the Pediatric Risk of Mortality II score (PRISM II) in the 12 hours before SCD initiation.33 The adult phase III study exclusion criteria were modified over the course of this pediatric study to be more relevant to children (Supplemental Table S1). For example, the use of extracorporeal membrane oxygenation (ECMO) was a contraindication, but ECMO is used commonly in pediatric sepsis, and after several screen failures based on ECMO, the FDA agreed to lift this exclusion. The institutional review board at each center approved the study prior to patient enrollment. Written informed consent was obtained from the subject's parents for those younger than 18 years of age, and/or a person with medical decision-making power for subjects 18 years of age or older prior to subject enrollment. Study personnel adhered to the Declaration of Helsinki. The study received an Investigational Device Exemption (G120174) from the US FDA and was registered at www.clinicaltrials.gov (NCT02820350) prior to study commencement. The study was funded mostly by an Office of Orphan Products Development grant (R01FD005092) from the US FDA with a small subsequent grant from SeaStar Medical Inc. to complete the final 2 subjects{\textquoteright} enrollment. As this was primarily a safety study (AEs and serious AEs [SAEs]), results and progress were reviewed by an external data safety monitoring board at least annually or at completion of 5, 10, and 16 subjects, whichever came first, to determine if any AEs occurred that would require study termination or modification. Funding Information: We conducted this prospective study at 4 US centers (Cincinnati Children{\textquoteright}s Hospital Medical Center, University of Michigan / CS Mott Children{\textquoteright}s Hospital, University of Alabama at Birmingham / Children{\textquoteright}s of Alabama, and Emory University / Children{\textquoteright}s Healthcare of Atlanta at Egleston). Children of 15 kg or more in weight, up to 22 years of age, who were admitted to an ICU were screened for eligibility. Subjects who had AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria, 29 and MOD and were receiving CKRT as part of the standard of clinical care were eligible to be enrolled in the study. MOD was defined as respiratory disease requiring invasive mechanical ventilation and/or cardiovascular compromise requiring the provision of a continuous infusion of an inotropic/vasoactive medication. These criteria have been repeatedly shown to be associated with AKI development and mortality in critically ill children. 30–32 Subject severity of illness was assessed by the Pediatric Risk of Mortality II score (PRISM II) in the 12 hours before SCD initiation. 33 The adult phase III study exclusion criteria were modified over the course of this pediatric study to be more relevant to children ( Supplemental Table S1 ). For example, the use of extracorporeal membrane oxygenation (ECMO) was a contraindication, but ECMO is used commonly in pediatric sepsis, and after several screen failures based on ECMO, the FDA agreed to lift this exclusion. The institutional review board at each center approved the study prior to patient enrollment. Written informed consent was obtained from the subject{\textquoteright}s parents for those younger than 18 years of age, and/or a person with medical decision-making power for subjects 18 years of age or older prior to subject enrollment. Study personnel adhered to the Declaration of Helsinki. The study received an Investigational Device Exemption (G120174) from the US FDA and was registered at www.clinicaltrials.gov ( NCT02820350 ) prior to study commencement. The study was funded mostly by an Office of Orphan Products Development grant ( R01FD005092 ) from the US FDA with a small subsequent grant from SeaStar Medical Inc. to complete the final 2 subjects{\textquoteright} enrollment. As this was primarily a safety study (AEs and serious AEs [SAEs]), results and progress were reviewed by an external data safety monitoring board at least annually or at completion of 5, 10, and 16 subjects, whichever came first, to determine if any AEs occurred that would require study termination or modification. Publisher Copyright: {\textcopyright} 2020 International Society of Nephrology",
year = "2021",
month = mar,
doi = "10.1016/j.ekir.2020.12.010",
language = "English (US)",
volume = "6",
pages = "775--784",
journal = "Kidney International Reports",
issn = "2468-0249",
publisher = "Elsevier Inc.",
number = "3",
}