Acute Kidney Injury
Conditions
Keywords
acute kidney injury, stem cells, aki, hope biosciences
Brief summary
This study aims to investigate, through the collection of valid scientific evidence necessary to determine safety and effectiveness, the potential use of Allogeneic Hope Biosciences Adipose-derived Mesenchymal Stem Cells (HB-adMSCs) to prevent progression of trauma-induced Acute Kidney Injury (AKI).
Detailed description
This multicenter, prospective, randomized, double-blind, placebo-controlled pragmatic Phase 1/Phase 2a clinical study aims to investigate, through the collection of valid scientific evidence necessary to determine safety and effectiveness, the potential use of adiposederived allogenic MSCs to prevent progression of trauma-induced AKI. We hypothesize that infusing a total of 3 doses of MSCs over 72 hours at 24-hour intervals starting in patients with modified KDIGO Stage 2 or 3 AKI will prove to be safe and efficacious. Phase 1 of the study will include Cohort 1 (10 patients) and will confirm safety in this population with this cell formulation (cryopreserved and reanimated). Phase 2a of the study will include 60 patients (30 interventional, 30 placebo) and will look at duration of AKI at Stage 2 or higher (defined as proportion of patients with a duration of Stage 2 AKI more than 2 days after the start of treatment).
Interventions
DRUGAllogeneic HB-adMSCs
Allogeneic HB-adMSCs
DRUGNormal Saline
Sterile Saline Solution
Sponsors
Hope Biosciences LLC
The University of Texas Health Science Center, Houston
University of California, San Francisco
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This multicenter, prospective, randomized, double-blind, placebo controlled pragmatic Phase 1/Phase 2a clinical study will enroll severely injured trauma or burn patients who have developed Stage 2 AKI. Eligible patients will be randomized to receive Hope Biosciences (HB)-adMSCs or placebo administered within 24 hours of consent and in 3 doses, each 24 hours apart. The investigators will enroll 10 patients in Cohort 1, the Phase 1 safety substudy. All patients in Cohort 1 will receive active investigational product (IP). The investigators will enroll 60 patients in Cohort 2, the Phase 2a substudy; 30 patients will receive active IP, and 30 will receive placebo via randomization. The study population is trauma and burn patients admitted to participating hospitals who meet the inclusion and exclusion criteria. The study population will be reflective of the general trauma population at the participating sites.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Between 18 and 75 years old AND 2. Diagnosed with Modified KDIGO Stage 2 AKI within the first 10 days after injury AND 3. Admitted to Intensive Care Unit or Intermediate Medical Unit AND 4. Received at least 3 units of any blood product within 6 hours of admission for trauma OR 15% or greater burn area OR any electrical burn OR any crush injury AND 5. Expected to survive at least 24 hours after diagnosis of KDIGO Stage 2 AKI AND 6. Patient or patient's Legally Authorized Representative (LAR) has voluntarily signed the informed consent.
Exclusion criteria
Patients are ineligible if they meet ONE OR MORE of the following: 1. Incarcerated individuals 2. Pregnant and lactating females 3. TBI deemed non-survivable by the trauma or neurosurgery attending physician 4. Hemodynamically unstable and requiring vasopressors for blood pressure support (systolic blood pressure ≥90 mmHg) during the 30-minute period prior to investigational product (IP) thawing/preparation 5. Pre-existing chronic kidney disease or acute kidney failure. 6. Pre-existing chronic liver disease. 7. Known immunodeficiency or concurrent use of potentially immunosuppressive medications at doses likely to result in an immunosuppressed status. 8. Active malignancy. 9. Known allergy to dimethyl sulfoxide or human serum albumin. 10. No available intravenous access (peripheral or central) of at least 22-gauge needle that can be utilized exclusively for IP during the time of planned infusion. 11. Clinical condition that would be anticipated to deteriorate with IV administration of 250 ml of crystalloid. 12. Known Do Not Resuscitate (DNR) prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of infusion-related adverse events (AEs) or serious adverse events (SAEs) | 1 year | Incidence of treatment-related adverse events (TEAEs) will be monitored to assess the safety of the infusion product on the patients in Phase 1 of the trial. |
| Duration of Acute Kidney Injury (AKI) at Stage 2 | 2 days | Proportion of patients with a duration of Stage 2 AKI more than 2 days after the start of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with progression of Kidney Disease Improving Global Outcomes (KDIGO) Stage 2 AKI | 1 year | The progression from Stage 2 to Stage 3 AKI often constitutes the initiation of renal replacement therapy (RRT), tripling of creatinine levels or creatinine \> 4 mg/dL with an increase of 0.5 mg/dL, with an associated marked increase in morbidity, mortality, and cost. |
| Mortality at 30, 90 days and 365 days | 1 year | Whether the patient remains alive or not at 1 month, 3 months, and 1 year |
| Post-injury organ dysfunction and thromboinflammation | 1 year | Includes incidence of sepsis, acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE; pulmonary embolism and deep venous thrombosis), and multiple organ failure (MOF) |
| Number of participants with chronic critical illness (≥14 days) | 1 year | Determined by prolonged intensive care unit (ICU) admission (≥14 days) with evidence of ongoing organ dysfunction |
| Severity of complications, including incidence of sepsis, ARDS, venous thromboembolism (VTE; pulmonary embolism and deep venous thrombosis), and multiple organ failure (MOF) | 1 year | Severity of each complication will be determined by complication-specific criteria, e.g. Berlin criteria (mild, moderate, severe) |
| Hospital-, ICU- and ventilator-free days | 1 year | Defined as the number of days a patient was not in the hospital or on the ventilator or in the ICU at 30 days or hospital discharge/death |
| Number of patients with Recurrent AKI during the same hospitalization | 1 year | Defined as the amount of patients who have several episodes of AKI in the same hospitalization |
Countries
United States
Contacts
CONTACTCharles S Cox, Jr., MD
PRINCIPAL_INVESTIGATORCharles S Cox, Jr., MD
The University of Texas Health Science Center, Houston
Outcome results
None listed