Neutrophil and Monocyte Deactivation Via the SeLective CytopheretIc Device - A Randomized Clinical Trial in Acute Kidney Injury

Official title

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

Overview

This randomized, controlled, pivotal study is intended to determine whether up to ten sequential 24-hour treatments with the Selective Cytopheretic Device (SCD) will improve survival in patients with Acute Kidney Injury (AKI) requiring continuous kidney replacement therapy (CKRT) when compared to CKRT alone (standard of care). This study is further intended to determine whether SCD therapy will reduce the duration of maintenance dialysis secondary to AKI. This study will enroll approximately 339 subjects across 30 US sites. Participants will be patients in an intensive care unit (ICU) setting with a diagnosis of AKI requiring CKRT.

Interventions

• Device Selective Cytopheretic Device
  The Selective Cytopheretic Device (SCD) is comprised of tubing, connectors, and a synthetic hollow fiber membrane cartridge. The device is connected in series to a commercially available CKRT hemofilter. Blood from the CKRT circuit is diverted after the CKRT hemofilter through to the extracapillary space (ECS) of the SCD cartridge. Blood circulates through the SCD ECS and then it is returned to the patient via the venous return line of the CKRT circuit. Regional citrate anticoagulation is used f
• Other Standard of Care
  Standard of care CKRT for the subject's condition, as appropriate

Primary outcome measures

• Composite endpoint of mortality or dialysis dependency at 90 days [Time frame: 90 days]

Secondary outcome measures (4)

• MAKE90 [Time frame: 90 days]
• Dialysis dependence [Time frame: 1 year]
• ICU free days in the first 28 days [Time frame: 28 days]
• Mortality at 28 days [Time frame: 28 days]

Eligibility criteria

Inclusion criteria

• Admitted to an ICU requiring CKRT:

• Must have AKI stage 2 or greater at the time of CKRT initiation.
• Must have been on CKRT for at least 12 hours but no greater than 48 hours at the time of enrollment.
• At least 18 years of age but not older than 80 at the time of enrollment.
• One additional life-threatening organ dysfunction present.
• Acceptable vascular access for CKRT to include adequate lumen size and length of catheters.
• Initial (non-binding) commitment to maintaining current level of care for at least 96 hours.
• C-Reactive Protein >3.5 mg/dl.

Exclusion criteria

• Not expected to survive next 24 hours.
• Anticipated transition to comfort measures or hospice in next 4 days.
• Terminal condition whereby the patient is not expected to survive 28 days or any condition in which therapy is regarded as futile by the PI.
• Advanced malignancy which is actively being treated or may be treated with palliative chemotherapy or radiation.
• ICU hospitalization > 14 days during this hospital admission (to include days spent at ICU of an outside hospital) at the time of screening.
• Active COVID-19 infection with a primary admission diagnosis of COVID-19.
• Chronic use of ventricular assist devices.
• ESRD requiring chronic kidney replacement therapy.
• History of CKD (greater than Stage 3).
• AKI stage 0 or stage 1 at the time of CKRT initiation.
• Non-ATN AKI diagnosis. We intend on relying on local nephrology subspecialty expertise to reasonably exclude non-ATN diagnoses based on clinical suspicions combined with prespecified objective criteria. If there is a reasonable suspicion that the subject has non-ATN AKI based on this, they will be excluded from the trial.
• Acute coronary syndromes, acute stroke, or acute major vascular compromise requiring medical or surgical interventions within 48 hours of randomization.
• Active hemorrhage requiring blood transfusions at the time of screening.
• Acute on Chronic Liver Failure.
• Suspicion of hepato-renal syndrome.
• Presence of any solid organ transplant at any time prior to admission.
• Severe burns with a modified Baux score > 100 (%TBSA+Age+17 for Inhalation Injury).
• Bone marrow transplant within the last year.
• Chronic immunosuppression with an average of >20 mg/day of prednisone or other steroid sparing immunosuppressants for the past 30 days prior to hospital admission.
• Individuals who have a history of primary or secondary immune disorders including, but not limited to, HIV or AIDS.
• Dry weight of >150kg.
• Platelet count <15,000/mm3.
• Patient is a prisoner or member of a vulnerable population.
• Patient is pregnant or breast feeding.
• Concurrent enrollment in another interventional clinical trial for an investigational drug or device.
• Need for plasmapheresis.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 38 centers

• University of Alabama Birmingham Hospital — Birmingham
• Mayo Clinic in Arizona — Phoenix
• Ronald Reagan UCLA Medical Center — Los Angeles
• Stanford University — Palo Alto
• University of California San Francisco — San Francisco
• University of Colorado Hospital Anschutz Medical Campus — Aurora
• Mayo Clinic in Florida — Jacksonville
• AdventHealth Orlando — Orlando
• … and 30 more centers

Publications

• Kjellstrand CM, Gornick C, Davin T. Recovery from acute renal failure. Clin Exp Dial Apheresis. 1981;5(1-2):143-61. doi: 10.3109/08860228109076011. PMID 7333033
• Hall JW, Johnson WJ, Maher FT, Hunt JC. Immediate and long-term prognosis in acute renal failure. Ann Intern Med. 1970 Oct;73(4):515-21. doi: 10.7326/0003-4819-73-4-515. No abstract available. PMID 5506002
• VA/NIH Acute Renal Failure Trial Network; Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008 Jul 3;359(1):7-20. doi: 10.1056/NEJMoa0802639. Epub 2008 May 20. PMID 18492867
• Palevsky PM, O'Connor TZ, Chertow GM, Crowley ST, Zhang JH, Kellum JA; US Department of Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network. Intensity of renal replacement therapy in acute kidney injury: perspective from within the Acute Renal Failure Trial Network Study. Crit Care. 2009;13(4):310. doi: 10.1186/cc7901. Epub 2009 Aug 11. PMID 19678919
• Van Den Noortgate N, Mouton V, Lamot C, Van Nooten G, Dhondt A, Vanholder R, Afschrift M, Lameire N. Outcome in a post-cardiac surgery population with acute renal failure requiring dialysis: does age make a difference? Nephrol Dial Transplant. 2003 Apr;18(4):732-6. doi: 10.1093/ndt/gfg043. PMID 12637642
• Liano F, Junco E, Pascual J, Madero R, Verde E. The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group. Kidney Int Suppl. 1998 May;66:S16-24. PMID 9580541
• Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005 Aug 17;294(7):813-8. doi: 10.1001/jama.294.7.813. PMID 16106006
• Metnitz PG, Krenn CG, Steltzer H, Lang T, Ploder J, Lenz K, Le Gall JR, Druml W. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med. 2002 Sep;30(9):2051-8. doi: 10.1097/00003246-200209000-00016. PMID 12352040

Identifiers

NCT: NCT05758077 · SCD-006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗