Hyperuricemia
Conditions
Keywords
cardiac surgery, hyperuricemia
Brief summary
Acute kidney injury is associated with a rise in serum uric acid during cardiovascular surgery and can cause poor blood flow to the kidneys making them vulnerable to kidney injury. We hypothesize that hyperuricemia, particularly if chronic and marked, is a risk factor for acute kidney injury. The preoperative lowering of serum uric acid will reduce the incidence of acute kidney injury following cardiovascular surgery.
Detailed description
The study will be a prospective, double-blind, placebo-controlled, randomized, clinical trial, initiated and implemented conjointly by the Nephrology and Cardiovascular Surgery Departments at Shands Hospital at the University of Florida in Gainesville, FL. We propose to study whether lowering uric acid provides significant renal and cardiovascular protection in subjects undergoing cardiovascular surgery. Up to 30 patients presenting for elective or urgent cardiovascular surgery with uric acid level \> 6.5 mg/dl and estimated glomerular filtration of 30 - 60 ml/min will be included in the study. Patients recruitment will continue until up to 30 patients have completed the study, taking into account expected patient loss due to withdrawal of consent, incomplete study and other reasons. Patients will be randomized to a control group or rasburicase group. Rasburicase or identical placebo will be administered to each group after randomization. A selected number of patients may undergo additional testing for mechanistic (non-clinical) secondary endpoints.
Interventions
DRUGRasburicase
Rasburicase (Dose: 7.5mg in 50ml of normal saline administered over 30 minutes) or identical placebo will be administered as an (dosage form)intravenous infusion preoperatively.
DRUGPlacebo
Placebo drug (color-coded to appear identical to study drug) administered as an (dosage form) intravenous infusion preoperatively.
Sponsors
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older, and 2. Undergoing elective cardiothoracic surgery(s), alone or in combination with other procedures/surgery(s): thoracic aortic aneurysm, cardiac valves, coronary artery bypass grafting, abdominal thoracic aneurysm, other CV surgery, and 3. Preoperative serum uric acid \> 6.5 mg/dL, and 4. Preoperative estimated glomerular filtration rate of \>30ml/min/1.73m2 or higher, but less than 60ml/min/1.73m2
Exclusion criteria
1. Prior history of allergy/adverse reaction to Rasburicase 2. History of any organ transplant 3. Preoperative intra-aortic balloon pump (IABP) 4. Known glucose 6-phosphate dehydrogenase (G6PD) deficiency 5. Current use of natriuretic peptides
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Acute Kidney Injury (AKI). | Within 48 hours postoperatively | Acute kidney injury will be defined as an increase in serum creatinine of 0.3mg/dL from baseline or a 50% increase in serum creatinine from baseline values within 48 hours after surgery. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the Cardiovascular Surgery clinics. Written consents were obtained from all patients.
Pre-assignment details
A large number of patients were screened to achieve the final participant numbers.
Participants by arm
| Arm | Count |
|---|---|
| Rasburicase Group The drug rasburicase was used in this group. | 13 |
| Placebo Group This group received an identical placebo of rasburicase. | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Rasburicase Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 13 Participants | 26 Participants |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Number of Patients With Acute Kidney Injury (AKI).
Acute kidney injury will be defined as an increase in serum creatinine of 0.3mg/dL from baseline or a 50% increase in serum creatinine from baseline values within 48 hours after surgery.
Time frame: Within 48 hours postoperatively
Population: As no similar study has been performed, a power analysis could not be performed. As such, we decided to do a pilot study with 26 subjects and to set criteria to maximize the likelihood of seeing an effect.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rasburicase Group | Number of Patients With Acute Kidney Injury (AKI). | 13 Participants |
| Placebo Group | Number of Patients With Acute Kidney Injury (AKI). | 13 Participants |