Acute Kidney Injury
Conditions
Keywords
Acute Renal Failure, Acute kidney injury, Acute tubular necrosis, Continuous Renal Replacement Therapy, Severe sepsis, Selective cytopheretic device
Brief summary
The purpose of this protocol is to evaluate the safety of a selective cytopheretic device (SCD) in patients that are on continuous renal replacement therapy (CRRT) for acute kidney injury (AKI).
Detailed description
Acute kidney injury is a condition where the kidneys are not capable of producing adequate urine. Therefore, another way to remove waste from the body is needed to hopefully allow time for the kidneys to heal. One method of removing waste from the body is called Continuous Renal Replacement Therapy (CRRT) or variations of that therapy. This study will evaluate the safety of the device while it is connected to the CRRT tubing for up to 7 days. Patients will be followed up until day 60 following the treatment.
Interventions
DEVICESCD
The selective cytopheretic device (SCD) is comprised of tubing, connectors and a hemofilter cartridge. The device is connected in series to a commercially available Continuous Renal Replacement Therapy (CRRT) device. Blood from the CRRT circuit is diverted after the CRRT hemofilter through to the extra capillary space (ECS) of the SCD. Blood circulates through this space and is returned to the patient via the venous return line of the CRRT circuit. Regional citrate anticoagulation is used for the entire CRRT and SCD blood circuits.
Sponsors
SeaStar Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. A patient, or legal representative, has signed a written informed consent form. 2. Must be receiving medical care in an intensive care unit (e.g., ICU, MICU, SICU, CTICU, Trauma). 3. Age 18 to 80 years. 4. Females of child bearing potential who are not pregnant (confirmed by a negative serum pregnancy test) and not lactating if recently post-partum. 5. Must be receiving and tolerating CRRT therapy for a minimum of 4 hours, but not longer than 24. 6. Expected to remain in the ICU for at least 96 hours after evaluation for enrollment. 7. A clinical diagnosis of ATN due to hemodynamic or toxic etiologies. ATN is defined as Acute Kidney Injury occurring in a setting of acute ischemic or nephrotoxic injury with oliguria (average \<20 mL/hr) for \>6-12 hours or: an increase in serum creatinine ≥2 mg/dL (≥1.5 mg/dL in females) over a period of ≤4 days. (Note: Prerenal, hepatorenal, vascular, interstitial, glomerular, and obstructive etiologies are excluded on clinical or other diagnostic grounds.) 8. Presence of at least one non-renal organ failure or present sepsis as defined in Appendix C. 9. All patients must be able to tolerate regional citrate anticoagulation.
Exclusion criteria
1. Irreversible brain damage based on available historical and clinical information. 2. Presence of any organ transplant at any time. 3. Acute or chronic use of circulatory support device such as LVADs, RVADs, BIVADs, ECMO. 4. Presence of preexisting advanced chronic renal failure (i.e., ESRD) requiring chronic renal replacement therapy prior to this episode of acute kidney injury. 5. AKI occurring in the setting of burns, obstructive uropathy, allergic interstitial nephritis, acute or rapidly progressive glomerulonephritis, vasculitis, hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura (TTP), malignant hypertension, scleroderma renal crisis, atheroembolism, functional or surgical nephrectomy, hepatorenal syndrome, cyclosporine or tacrolimus nephrotoxicity. 6. Metastatic malignancy which is actively being treated or may be treated by chemotherapy or radiation during the subsequent three month period after study therapy. 7. Chronic immunosuppression (e.g., HIV/AIDS, chronic glucocorticoid therapy \>20 mg/day prednisone equivalent on a chronic basis). The acute use of glucocorticoids is permissible. 8. Severe liver failure as documented by a Child-Pugh Liver Failure Score \>12 (see Appendix F). 9. Currently in Do Not Resuscitate (DNR) status or DNR status anticipated within the next 7 days. 10. Currently in Comfort measures Only or Comfort Measures Only status anticipated within next 7 days. 11. Patient is moribund or chronically debilitated for whom full supportive care is not indicated. 12. Patient not expected to survive 28 days because of an irreversible medical condition. (This is not restrictive to AKI, and may include situations such as the presence of irreversible brain damage, untreatable malignancy, inoperable life threatening condition, or any condition to which therapy is regarded as futile by the PI.) 13. Any medical condition that the Investigator thinks may interfere with the study objectives. 14. Physician refusal. 15. Patient is a prisoner. 16. Dry weight of \>150 kg. 17. More than one hemodialysis treatment during this hospital admission or prior to transfer from an outside hospital. 18. Platelet count \<30,000/mm3 at time of screening. 19. Concurrent enrollment in another interventional clinical trial. Patients enrolled in clinical trials where only measurements and/or samples are taken (NO TEST DEVICE OR TEST DRUG USED) are allowed to participate. 20. Use of any other Investigational drug or device within the previous 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Clinical Efficacy Endpoint in This Trial is All Cause Mortality Through 60 Days Post-randomization. | Day 60 following treatment initiation | All cause mortality through day 60 post-randomization. The outcome data reported here describe the mortality at Day 60 (primary endpoint) of the treated subjects which received the recommended ionized calcium (riCa) for ≥ 90% of treatment time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Replacement Therapy Dependency at Day 60. | Day 60 following treatment initiation | RRT dependency at day 60 is defined as patient not receiving any form of intermittent or continuous renal replacement therapy at 60 days post enrollment in the study with no plans for additional intermittent or continuous renal replacement therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CRRT + SCD Patients with a diagnosis acute kidney injury with multiorgan failure requiring CRRT will be randomized.
SCD: The selective cytopheretic device (SCD) is comprised of tubing, connectors and a hemofilter cartridge. The device is connected in series to a commercially available Continuous Renal Replacement Therapy (CRRT) device. Blood from the CRRT circuit is diverted after the CRRT hemofilter through to the extra capillary space (ECS) of the SCD. Blood circulates through this space and is returned to the patient via the venous return line of the CRRT circuit. Regional citrate anticoagulation is used for the entire CRRT and SCD blood circuits. | 69 |
| CRRT Alone Patients with a diagnosis acute kidney injury with multiorgan failure requiring CRRT will be randomized. | 65 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 27 | 21 |
| Overall Study | Lost to Follow-up | 0 | 6 |
Baseline characteristics
| Characteristic | CRRT + SCD | Total | CRRT Alone |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 13.1 | 55.4 years STANDARD_DEVIATION 14 | 53.5 years STANDARD_DEVIATION 14.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 29 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 53 Participants | 101 Participants | 48 Participants |
| Region of Enrollment United States | 69 participants | 134 participants | 65 participants |
| Sex: Female, Male Female | 27 Participants | 52 Participants | 25 Participants |
| Sex: Female, Male Male | 42 Participants | 82 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 27 / 69 | 21 / 59 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 45 / 69 | 40 / 63 |
Outcome results
Primary
The Primary Clinical Efficacy Endpoint in This Trial is All Cause Mortality Through 60 Days Post-randomization.
All cause mortality through day 60 post-randomization. The outcome data reported here describe the mortality at Day 60 (primary endpoint) of the treated subjects which received the recommended ionized calcium (riCa) for ≥ 90% of treatment time.
Time frame: Day 60 following treatment initiation
Population: Outcome data is reported for those subjects in which the calcium levels were maintained in the protocol's recommended range (≤0.4 mmol/L) for greater or equal to 90% of the therapy time.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CRRT + SCD | The Primary Clinical Efficacy Endpoint in This Trial is All Cause Mortality Through 60 Days Post-randomization. | Alive | 16 Participants |
| CRRT + SCD | The Primary Clinical Efficacy Endpoint in This Trial is All Cause Mortality Through 60 Days Post-randomization. | Dead | 3 Participants |
| CRRT Alone | The Primary Clinical Efficacy Endpoint in This Trial is All Cause Mortality Through 60 Days Post-randomization. | Alive | 16 Participants |
| CRRT Alone | The Primary Clinical Efficacy Endpoint in This Trial is All Cause Mortality Through 60 Days Post-randomization. | Dead | 11 Participants |
Secondary
Renal Replacement Therapy Dependency at Day 60.
RRT dependency at day 60 is defined as patient not receiving any form of intermittent or continuous renal replacement therapy at 60 days post enrollment in the study with no plans for additional intermittent or continuous renal replacement therapy.
Time frame: Day 60 following treatment initiation
Population: per protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRRT + SCD | Renal Replacement Therapy Dependency at Day 60. | 3 Participants |
| CRRT Alone | Renal Replacement Therapy Dependency at Day 60. | 15 Participants |