Cardiac Surgery Associated - Acute Kidney Injury
Conditions
Brief summary
The is a two-stage study. Stage 1 is to evaluate the safety, tolerability, PK and PD of ENN0403 in patients at high risk of AKI following elective cardiac surgery requring cardiopulmonary bypass. Stage 2 is to evaluate the efficacy, safety, PK and PD of ENN0403 to prevent and treat AKI after multiple administraions in patients at high risk of AKI following elective cardiac surgery requring cardiopulmonary bypass.
Interventions
DRUGENN0403 capsules, low dose
ENN0403 capsules will be orally administered once a day for 5 consecutive days at low dose based on the standard treatment after cardiac surgery. If the subject is unable to swallow the investigational product autonomously, the capsules will be administrated through a nasogastric tube/oral gastric tube.
DRUGENN0403 capsules, high dose
ENN0403 capsules will be orally administered once a day for 5 consecutive days at high dose based on the standard treatment after cardiac surgery. If the subject is unable to swallow the investigational product autonomously, the placebo capsules will be administrated through a nasogastric tube/oral gastric tube.
DRUGPlacebo
Placebo capsules will be orally administered once a day for 5 consecutive days based on the standard treatment after cardiac surgery. If the subject is unable to swallow the investigational product autonomously, the capsules will be administrated through a nasogastric tube/oral gastric tube.
Sponsors
EnnovaBio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to understand and comply with the study requirements and able to provide written informed consent; 2. Age ≥18 and ≤85 years; 3. Male subjects (and their fertile female spouses/partners) do not have pregnancy plans during the screening period and within 3 months after the last dose, voluntarily take highly effective contraception, and must not donate sperm or ova. Only non-fertile women will be enrolled, and female subjects who meet the following criteria are not considered fertile: Postmenopausal status has been achieved, normal menstruation has stopped for at least 12 consecutive months with an FSH \>30 IU/L in the absence of other pathophysiological causes, or there is a medical record showing hysterectomy \\ bilateral tubal resection and/or bilateral ovariectomy. 4. Subjects must be scheduled for cardiac surgery requring cardiopulmonary bypass: Coronary artery bypass grafting (CABG) and/or heart valve surgery and/or aortic root, ascending aorta and aortic arch surgery; 5. Subjects have the risk of developing AKI with at least one of the following criteria: coronary artery bypass grafting combined with one or more heart valves surgery plus at least one risk factor for AKI; Multiple heart valves surgery plus at least one AKI risk factor; Coronary artery bypass grafting or aortic valve surgery combined with aortic root, ascending aorta, and aortic arch surgery (non-aortic dissection) plus at least one risk factor for AKI; Coronary artery bypass grafting alone or single heart valve surgery plus at least 2 risk factors for AKI.
Exclusion criteria
1. Receive ICD or permanent pacemaker implantation, mechanical ventilation, IABP, LVAD or other mechanical circulatory AIDS within 1 week before surgery; 2. Cardiopulmonary resuscitation is performed within 14 days prior to screening; 3. Abnormal renal function with eGFR\<20 mL/min/1.73 m2 within 30 days before screening; 4. Receive renal replacement therapy or the presence of AKI within 30 days before surgery, except for transient (≤5 days) stage 1 AKI after iodized contrast agent exposure; 5. Participate in other clinical trials within the past 1 month; 6. Have a known allergy to investigational drug or any of its constituents, or allery to any constituents used during the study; 7. Subjects with intractable hypotension, severe hypoxemia or other emergency during surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events (AE) and serious adverse events (SAE) | 30 days |
| Percentage of subjects developing AKI in different AKI stages based on Serum Creatinine and/or Urine Output per KDIGO definition | 5 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of subjects developing AKI in different AKI stages based on Serum Creatinine and/or Urine Output per KDIGO definition | 3 days, 7 days | — |
| Major Adverse Kidney Event (MAKE) at Day 30 | Day 30 | major adverse kidney events at 30 day (MAKE30) defined as the proportion of patients developing at least one of the following: death, need for renal replacement therapy, or ≥25% reduction in eGFR from baseline |
| Length of stay in the intensive care unit (ICU) and hospital | 30 days | — |
| Percentage of subjects developing AKI in different AKI stages based on Serum Creatinine per KDIGO definition | 5 days | — |
Countries
China
Contacts
Primary ContactXiaoyu Ma
Outcome results
None listed