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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rasburicase | Active Comparator | patients receiving rasburicase to lower serum uric acid |
|
| Placebo | Placebo Comparator | patients will receive a placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rasburicase | Drug | 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| A. Ahsan Ejaz, MD | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida | Gainesville | Florida | 32610 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17699382 | Background | Ejaz AA, Mu W, Kang DH, Roncal C, Sautin YY, Henderson G, Tabah-Fisch I, Keller B, Beaver TM, Nakagawa T, Johnson RJ. Could uric acid have a role in acute renal failure? Clin J Am Soc Nephrol. 2007 Jan;2(1):16-21. doi: 10.2215/CJN.00350106. Epub 2006 Dec 6. |
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A large number of patients were screened to achieve the final participant numbers.
Patients were recruited from the Cardiovascular Surgery clinics. Written consents were obtained from all patients.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rasburicase Group | The drug rasburicase was used in this group. |
| FG001 | Placebo Group | This group received an identical placebo of rasburicase. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rasburicase Group | The drug rasburicase was used in this group. |
| BG001 | Placebo Group | This group received an identical placebo of rasburicase. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Number | Participants | Within 48 hours postoperatively |
|
No Adverse Events occurred during the 15 months when data was collected.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rasburicase Group | The drug rasburicase was used in this group. |
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The limitation of the pilot study is that it was not powered to provide definite answers, an inherent limitation attributed to the absence of similar studies.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| A. Ahsan Ejaz, M.D. | University of Florida | 3522735328 | ejazaa@medicine.ufl.edu |
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| ID | Term |
|---|---|
| D033461 | Hyperuricemia |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C469709 | rasburicase |
| D005079 | Excipients |
| ID | Term |
|---|---|
| D014677 | Pharmaceutical Vehicles |
| D010592 | Pharmaceutic Aids |
| D004364 | Pharmaceutical Preparations |
| D020313 | Specialty Uses of Chemicals |
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|
| Placebo | Drug | Placebo drug (color-coded to appear identical to study drug) administered as an (dosage form) intravenous infusion preoperatively. |
|
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
The patients which received a placebo identical to rasburicase.
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| EG001 | Placebo Group | This group received an identical placebo of rasburicase. | 0 | 13 | 0 | 13 |
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| D020164 | Chemical Actions and Uses |