RasbAKI: Lowering Serum Uric Acid to Prevent Acute Kidney Injury

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT00756964
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperuricemia	Drug: Rasburicase; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Effect of Rasburicase on Acute Kidney Injury, Kidney Function, the Incidence of Renal Replacement Therapy and All-cause Mortality Following Cardiac Surgery.
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610

Sponsors and Collaborators

• University of Florida

Investigators

• Principal Investigator: A. Ahsan Ejaz, MD, University of Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Epub 2006 Dec 6. Review.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT00756964
• Other Study ID Numbers: WIRB 20081132
• First Posted: Sep 22, 2008
• Last Update Posted: Sep 3, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by University of Florida: cardiac surgery; hyperuricemia
• Additional relevant MeSH terms: Acute Kidney Injury; Hyperuricemia; Rasburicase

Study Results

Participant Flow

Recruitment Details	Patients were recruited from the Cardiovascular Surgery clinics. Written consents were obtained from all patients.
Pre-assignment Detail	A large number of patients were screened to achieve the final participant numbers.

Arm/Group Title	Rasburicase Group	Placebo Group
Arm/Group Description	The drug rasburicase was used in this group.	This group received an identical placebo of rasburicase.
Period Title: Overall Study
STARTED	13	13
COMPLETED	13	13
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Rasburicase Group	Placebo Group	Total
Arm/Group Description	The drug rasburicase was used in this group.	This group received an identical placebo of rasburicase.	Total of all reporting groups
Overall Participants	13	13	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	13 100%	26 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 30.8%	4 30.8%	8 30.8%
Male	9 69.2%	9 69.2%	18 69.2%
Region of Enrollment (participants) [Number]
United States	13 100%	13 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Acute Kidney Injury (AKI).
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Rasburicase Group	Placebo Group
Arm/Group Description	The patients received the drug rasburicase 7.5mg in 50mL of normal saline over 30 minutes period	The patients which received a placebo identical to rasburicase.
Measure Participants	13	13
Number [Participants]	13 100%	13 100%

Adverse Events

Time Frame	No Adverse Events occurred during the 15 months when data was collected.
Arm/Group Title	Rasburicase Group		Placebo Group
Arm/Group Description	The drug rasburicase was used in this group.		This group received an identical placebo of rasburicase.
All Cause Mortality
	Rasburicase Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rasburicase Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Rasburicase Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.