Efficacy Study of a Selective Cytopheretic Device (SCD) in Patients With Acute Kidney Injury

• Sponsor: SeaStar Medical (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01400893
• Collaborator: (none)
• Enrollment: 134
• Locations: 26
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Device: SCD	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 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 (SCD) In Patients With Acute Kidney Injury (AKI)
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CRRT + SCD Patients with a diagnosis of AKI requires CRRT will be randomized	Device: 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.
No Intervention: CRRT alone Patients with a diagnosis of AKI requires CRRT will be randomized

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States	35233
2	UCLA	Los Angeles	California	United States	90025
3	University of California, San Diego	San Diego	California	United States	92103
4	University of Florida	Gainesville	Florida	United States	32611
5	University of Florida	Jacksonville	Florida	United States	32209
6	Northwestern University	Chicago	Illinois	United States	60611
7	University of Iowa	Iowa City	Iowa	United States	52242
8	University of Maryland	Baltimore	Maryland	United States	21201
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	Beth Isreal Deaconess Medical Center	Boston	Massachusetts	United States	02215
11	Baystate Medical Center	Springfield	Massachusetts	United States	01199
12	Henry Ford Hospital	Detroit	Michigan	United States	48202
13	University of Mississippi	Jackson	Mississippi	United States	39216
14	Washington University	Saint Louis	Missouri	United States	63110
15	Albany Medical College	Albany	New York	United States	12208
16	Mount Sinai School of Medicine	New York	New York	United States	10029
17	Sanford Health	Fargo	North Dakota	United States	58122
18	Cleveland Clinic	Cleveland	Ohio	United States	44195
19	Medical University Of South Carolina	Charleston	South Carolina	United States	29425
20	Memorial Hospital	Chattanooga	Tennessee	United States	37403
21	Erlanger Hospital	Chattanooga	Tennessee	United States	37404
22	Dallas VA Medical Center	Dallas	Texas	United States	75216
23	University of Texas	Houston	Texas	United States	77030
24	INOVA Health Care Services	Falls Church	Virginia	United States	22042
25	Virginia Commonwealth University	Richmond	Virginia	United States	23298
26	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• SeaStar Medical

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: SeaStar Medical
• ClinicalTrials.gov Identifier: NCT01400893
• Other Study ID Numbers: SCD-003
• First Posted: Jul 25, 2011
• Last Update Posted: Apr 27, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by SeaStar Medical: Acute Renal Failure; Acute kidney injury; Acute tubular necrosis; Continuous Renal Replacement Therapy; Severe sepsis; Selective cytopheretic device
• Additional relevant MeSH terms: Acute Kidney Injury; Wounds and Injuries

Study Results

Participant Flow

Arm/Group Title	CRRT + SCD	CRRT Alone
Arm/Group Description	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.	Patients with a diagnosis of acute kidney injury and multiorgan failure requiring CRRT will be randomized
Period Title: Overall Study
STARTED	69	65
COMPLETED	42	38
NOT COMPLETED	27	27

Baseline Characteristics

Arm/Group Title	CRRT + SCD	CRRT Alone	Total
Arm/Group Description	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.	Patients with a diagnosis acute kidney injury with multiorgan failure requiring CRRT will be randomized.	Total of all reporting groups
Overall Participants	69	65	134
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.2 (13.1)	53.5 (14.7)	55.4 (14)
Sex: Female, Male (Count of Participants)
Female	27 39.1%	25 38.5%	52 38.8%
Male	42 60.9%	40 61.5%	82 61.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	15 21.7%	14 21.5%	29 21.6%
White	53 76.8%	48 73.8%	101 75.4%
More than one race	1 1.4%	2 3.1%	3 2.2%
Unknown or Not Reported	0 0%	1 1.5%	1 0.7%
Region of Enrollment (participants) [Number]
United States	69 100%	65 100%	134 100%

Outcome Measures

1. Primary Outcome

Title	The Primary Clinical Efficacy Endpoint in This Trial is All Cause Mortality Through 60 Days Post-randomization.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	CRRT + SCD	CRRT Alone
Arm/Group Description	Patients with a diagnosis of AKI requires 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.	Patients with a diagnosis of AKI requires CRRT will be randomized
Measure Participants	19	27
Alive	16 23.2%	16 24.6%
Dead	3 4.3%	11 16.9%

2. Secondary Outcome

Title	Renal Replacement Therapy Dependency at Day 60.
Description	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

Outcome Measure Data

Analysis Population Description

per protocol.

Arm/Group Title	CRRT + SCD	CRRT Alone
Arm/Group Description	Patients with a diagnosis of AKI 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.	Patients with a diagnosis of AKI will be randomized
Measure Participants	19	26
Count of Participants [Participants]	3 4.3%	15 23.1%

Adverse Events

Time Frame	Up to 7 days of SCD treatment or control. This time frame differs from the primary outcome measure of 60 day mortality since therapy was provided up to 7 days of SCD treatment. The adverse events were captured only during SCD treatment times since device related events would occur at that time frame. ITT patients are included in this table.
Adverse Event Reporting Description	Trial results showed that a number of enrollees in the treated and control arms deviated from protocol requiring regional citrate anticoagulation due to a national shortage of injectable CaCl2. The Primary Outcome is reported for patients who were treated per protocol. Two subjects enrolled to CRRT alone arm were not treated, so not counted in SAEs. 60 Day Mortality does not include 6 subjects LTFU. Other Adverse Events were not collected.
Arm/Group Title	CRRT + SCD		CRRT Alone
Arm/Group Description	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.		Patients with a diagnosis acute kidney injury with multiorgan failure requiring CRRT will be randomized.
All Cause Mortality
	CRRT + SCD		CRRT Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/69 (39.1%)		21/59 (35.6%)
Serious Adverse Events
	CRRT + SCD		CRRT Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/69 (65.2%)		40/63 (63.5%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	8/69 (11.6%)	8	3/63 (4.8%)	3
Cardiac disorders
Cardiac disorders	12/69 (17.4%)	12	10/63 (15.9%)	10
Gastrointestinal disorders
Gastrointestinal disorders	4/69 (5.8%)	4	6/63 (9.5%)	6
General disorders
General disorders and administration site conditions	4/69 (5.8%)	4	7/63 (11.1%)	7
Infections and infestations
Infections and infestations	12/69 (17.4%)	12	10/63 (15.9%)	10
Injury, poisoning and procedural complications
Injury, poisoning and procedural conplications	1/69 (1.4%)	1	0/63 (0%)	0
Investigations
Investigations	0/69 (0%)	0	1/63 (1.6%)	1
Metabolism and nutrition disorders
Metabolism and nutrition disorders	2/69 (2.9%)	2	2/63 (3.2%)	2
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	1/69 (1.4%)	1	1/63 (1.6%)	1
Psychiatric disorders
Psychiatric disorders	0/69 (0%)	0	1/63 (1.6%)	1
Renal and urinary disorders
Renal and urinary disorders	1/69 (1.4%)	1	3/63 (4.8%)	3
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	10/69 (14.5%)	10	10/63 (15.9%)	10
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	0/69 (0%)	0	2/63 (3.2%)	2
Vascular disorders
Vascular disorders	7/69 (10.1%)	7	4/63 (6.3%)	4
Other (Not Including Serious) Adverse Events
	CRRT + SCD		CRRT Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.