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

Sponsor

SeaStar Medical (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05758077

Collaborator

ICON plc (Industry)

200

Enrollment

Locations

Arms

32.1

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 200 subjects across 30 US sites. Participants will be patients in an intensive care unit (ICU) setting with a diagnosis of AKI requiring CKRT.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Device: Selective Cytopheretic Device Other: Standard of Care	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SCD + CKRT Arm In addition to standard of care CKRT therapy for these subjects, these subjects will have up to ten sequential 24-hour treatments with the Selective Cytopheretic Device (SCD) in-line with their existing CKRT circuit.	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 for the entire CKRT and SCD blood circuit. The SCD cartridge incorporates a synthetic hollow fiber membrane with the ability to bind activated leukocytes to its extracapillary surface; and when used in a CKRT extracorporeal circuit in the presence of regional citrate anticoagulation, the SCD modulates inflammation. Other Names: SCD
Other: CKRT Alone Arm (standard of care) This arm will receive standard of care CKRT therapy for their condition as appropriate.	Other: Standard of Care Standard of care CKRT for the subject's condition, as appropriate

Arm

Intervention/Treatment

Experimental: SCD + CKRT Arm

In addition to standard of care CKRT therapy for these subjects, these subjects will have up to ten sequential 24-hour treatments with the Selective Cytopheretic Device (SCD) in-line with their existing CKRT circuit.

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 for the entire CKRT and SCD blood circuit. The SCD cartridge incorporates a synthetic hollow fiber membrane with the ability to bind activated leukocytes to its extracapillary surface; and when used in a CKRT extracorporeal circuit in the presence of regional citrate anticoagulation, the SCD modulates inflammation.

Other Names:

SCD

Other: CKRT Alone Arm (standard of care)

This arm will receive standard of care CKRT therapy for their condition as appropriate.

Other: Standard of Care

Standard of care CKRT for the subject's condition, as appropriate

Outcome Measures

Primary Outcome Measures

Composite endpoint of mortality or dialysis dependency at 90 days [90 days]
The composite of death or requiring kidney replacement therapy at 90 days post randomization

Secondary Outcome Measures

MAKE90 [90 days]
Major adverse kidney events at day 90 is a composite of death, need for KRT, or persistent renal dysfunction (final serum creatinine concentration, ≥200% of the baseline value) at the 90 day follow up period
Dialysis dependence [1 year]
Need for any form of kidney replacement therapy at one year
ICU free days in the first 28 days [28 days]
The number of days alive and requiring ICU level of care in the 28 days after randomization for at least 24 hours
Mortality at 28 days [28 days]
Death by day 28 post randomization

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 (at least 11.5 Fr for IJ, 13.5 Fr for femoral), and length of catheters (15cm for IJ, 24cm for femoral sites).
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.
Malignancy which is actively being treated or may be treated by chemotherapy or radiation.
Hospitalization >14 days during this hospital admission and/or prior transfer from an outside hospital at the time of screening.
Active COVID-19 infection with a primary admission diagnosis of COVID-19.
Acute or chronic use of ventricular assist devices.
ESRD requiring chronic kidney replacement therapy.
History of CKD (greater than Stage 2).
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 >30% total body surface area.
Bone marrow transplant within the last year.
Chronic immunosuppression.
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.
Use of any other investigational drug or device within the previous 30 days.
Requiring plasmapheresis for any reason during the hospitalization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SeaStar Clinical Trial Site	Little Rock	Arkansas	United States	72205
2	SeaStar Clinical Trial Site	Aurora	Colorado	United States	80045
3	SeaStar Clinical Trial Site	Augusta	Georgia	United States	30909
4	SeaStar Clinical Trial Site	Ann Arbor	Michigan	United States	48109
5	SeaStar Clinical Trial Site	Detroit	Michigan	United States	48202
6	SeaStar Clinical Trial Site	Cincinnati	Ohio	United States	45219
7	SeaStar Clinical Trial Site	Corvallis	Oregon	United States	97330
8	SeaStar Clinical Trial Site	San Antonio	Texas	United States	78229
9	SeaStar Clinical Trial Site	Norfolk	Virginia	United States	23507
10	SeaStar Clinical Trial Site	Richmond	Virginia	United States	23219