Lowering Serum Uric Acid to Prevent Acute Kidney Injury

Study Overview
=================
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.

Official Title
-----------------
Effect of Rasburicase on Acute Kidney Injury, Kidney Function, the Incidence of Renal Replacement Therapy and All-cause Mortality Following Cardiac Surgery.

Conditions
-----------------
Hyperuricemia

Intervention / Treatment
-----------------
* Drug: Rasburicase
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years or older, and 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 Preoperative serum uric acid > 6.5 mg/dL, and Preoperative estimated glomerular filtration rate of >30ml/min/1.73m2 or higher, but less than 60ml/min/1.73m2 Exclusion Criteria: Prior history of allergy/adverse reaction to Rasburicase History of any organ transplant Preoperative intra-aortic balloon pump (IABP) Known glucose 6-phosphate dehydrogenase (G6PD) deficiency Current use of natriuretic peptides

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rasburicase<br>patients receiving rasburicase to lower serum uric acid | Drug: Rasburicase<br>* 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.<br>* Other names: urate oxidase enzyme;|
| Placebo Comparator: Placebo<br>patients will receive a placebo | Drug: Placebo<br>* Placebo drug (color-coded to appear identical to study drug) administered as an (dosage form) intravenous infusion preoperatively.<br>* Other names: inactive ingredient;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Within 48 hours postoperatively | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cardiac surgery, hyperuricemia