Use of the Selective Cytopheretic Device to Support Critically Ill Children Requiring Continuous Renal Replacement Therapy: A Probable Benefit-Risk Assessment

Background Critically ill children with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CRRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect when circuit 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 have conducted two multicenter studies to evaluate safety and feasibility of the SCD in critically ill children with AKI receiving CRRT and multiorgan failure. We report the combined efficacy and safety data from these two studies for the first time. Methods Four pediatric institutions enrolled children >10 kg in size with AKI and multiorgan dysfunction (MODS) receiving CRRT as part of standard of care to receive the SCD integrated post CRRT membrane. RCA was used to achieve a circuit iCa2+<0.40 mmol/L. We report serious adverse events, patient and CRRT-SCD related process and outcome variables and perform a Bayesian analysis to provide potential attributable benefit-risk assessment of SCD support in this critically ill population using a published matched cohort for the control population. Results Twenty-two patients (10 females) from the two studies comprise the combined population; 21 received mechanical ventilation, 14 received vasoactive medications, three received extracorporeal membrane oxygenation and 15 had sepsis at the time of CRRT-SCD initiation. Median SCD treatment duration was six days. Fifteen total serious adverse events were recorded, none of which were SCD related. All but one patient survived to the time of SCD discontinuation. Seventeen patients survived 60 days and 16 patients survived to the time ICU discharge. Fourteen patients surviving to ICU discharge had a normal eGFR and no patient was dialysis dependent at 60 days after CRRT-SCD initiation. Bayesian analyses revealed a 98-99% probable benefit of addition of SCD support. Conclusion These data suggest SCD therapy is feasible, safe and demonstrates probably benefit for children who require CRRT for AKI in the setting of MODS. ### Competing Interest Statement Dr Goldstein receives consulting fees from SeaStar Medical Inc to assist with their application for a Humanitarian Device Exemption from the US FDA for SCD technology SeaStar Medical was not involved in the execution of this study including patient enrollment data acquisition data analysis or development of this manuscript Dr Humes relevant disclosures include Innovative Biotherapies Inc shareholder officer director SeaStar Medical shareholder scientific advisor consultant Silicon Kidney scientific advisor ### Clinical Trial NCT02820350 and [NCT04869787][1] ### Funding Statement SCD PED-01 was funded mostly by an Office of Orphan Products Development (OOPD) grant (R01FD005092) from the US FDA with a small subsequent grant from SeaStar Medical Inc to complete the final two subjects enrollment SCD PED-02 was funded by the Frankel Innovation Initiative at the University of Michigan ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted at four 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. The Institutional Review Board at each center approved the study prior to patient enrollment at their site. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04869787&atom=%2Fmedrxiv%2Fearly%2F2023%2F08%2F22%2F2023.08.22.23294378.atom