Acute Kidney Injury
Conditions
Keywords
coronary artery bypass surgery, ouabain, acute kidney injury
Brief summary
Acute kidney injury (AKI) occurs in up to 30% of patients undergoing coronary artery bypass graft (CABG) surgery, and often requires patients to go on dialysis. In patients needing dialysis, the risk of dying is very high.There are no known therapies to reduce the chance of developing kidney damage after heart surgery. There is evidence that patients with high levels of a substance called ouabain have an increased risk of developing kidney damage. This study is testing the hypothesis that giving a medication called DigiFab to lower the ouabain levels will reduce the risk of developing kidney damage after heart surgery.
Detailed description
This is a randomized double-blinded study investigating the role of DigiFab in patients with elevated risk of acute kidney injury undergoing CABG surgery. University of Maryland Medical Center (UMMC) and University of Maryland St Joseph Medical Center (UMSJMC) patients who are undergoing CABG, meet the inclusion criteria and provide consent will be enrolled in this study and randomized to either DigiFab arm or the placebo (vehicle) arm. The study involves a follow up period of 72 hours post CABG surgery.
Interventions
DRUGDigoxin Antibodies Fab Fragments
Digoxin antibodies
OTHERPlacebo
Saline
DIAGNOSTIC_TESTBaseline EO > 360 pM
Baseline ouabain concentration \> 360 pM
DIAGNOSTIC_TESTEO < 360 pM
Baseline ouabain concentration \< 360 pM
Sponsors
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigational pharmacy will provide active drug or placebo
Intervention model description
Patients undergoing coronary artery bypass surgery
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Undergoing coronary artery bypass surgery * glomerular filtration rate \> 15 History of Diabetes Mellitus or GFR \< 60
Exclusion criteria
* Allergy to Digifab Contrast dye within 3 days Creatinine \> 25% above baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal Function | 72 hours | Change in glomerular filtration rate (measured by Cockcroft-Gault Formula), mL/min per 1.73 m2 from baseline to 72 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AKI | 3 days | Development of AKI at 72 hours |
Countries
United States
Participant flow
Pre-assignment details
Patients randomized and double blinded
Participants by arm
| Arm | Count |
|---|---|
| Digifab Below Median Received Digifab with baseline ouabain below median | 70 |
| Placebo Below Median Received placebo with baseline ouabain below median | 64 |
| Digifab Above Median Digifab intravenous with baseline ouabain above median | 64 |
| Placebo Above Median saline intravenous with baseline ouabain above median | 69 |
| Total | 267 |
Baseline characteristics
| Characteristic | Digifab Below Median | Total | Placebo Above Median | Digifab Above Median | Placebo Below Median |
|---|---|---|---|---|---|
| Age, Continuous | 66 years | 67 years | 70 years | 65 years | 67 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 8 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 39 Participants | 5 Participants | 9 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 201 Participants | 59 Participants | 49 Participants | 39 Participants |
| Sex: Female, Male Female | 15 Participants | 60 Participants | 16 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Male | 51 Participants | 190 Participants | 50 Participants | 44 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 2 / 66 | 1 / 66 | 2 / 59 |
| other Total, other adverse events | 0 / 59 | 0 / 66 | 0 / 66 | 0 / 59 |
| serious Total, serious adverse events | 17 / 59 | 20 / 66 | 14 / 66 | 16 / 59 |
Outcome results
Primary
Renal Function
Change in glomerular filtration rate (measured by Cockcroft-Gault Formula), mL/min per 1.73 m2 from baseline to 72 hours
Time frame: 72 hours
Population: Randomized study with endpoint assessed in those with baseline ouabain concentration (EO) above and below 360 pM
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Digifab, EO > 360 | Renal Function | .46 mL/min/1.73m^2 |
| Placebo, EO > 360 | Renal Function | .75 mL/min/1.73m^2 |
| Digifab, Eo < 360 | Renal Function | 4.26 mL/min/1.73m^2 |
| Placebo, EO < 360 | Renal Function | 2.80 mL/min/1.73m^2 |
p-value: >0.05Regression, Linear
p-value: <0.05Regression, Logistic
Secondary
AKI
Development of AKI at 72 hours
Time frame: 3 days
Population: Results by intervention and baseline ouabain concentration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Digifab, EO > 360 | AKI | 5 participants |
| Placebo, EO > 360 | AKI | 12 participants |
| Digifab, Eo < 360 | AKI | 8 participants |
| Placebo, EO < 360 | AKI | 8 participants |