Lowering Serum Uric Acid to Prevent Acute Kidney Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lowering Serum Uric Acid to Prevent Acute Kidney Injury (NCT00756964), a randomized phase 2 study. The primary outcome is Number of Patients With Acute Kidney Injury (AKI)..

2. Clinical Question

The clinical rationale recorded for the trial links cardiovascular surgery, a rise in serum uric acid, and vulnerability of the kidneys to injury. The summary further proposes that chronic and marked hyperuricemia could be a risk factor. These are the rationale and hypothesis recorded by the investigators, not conclusions established by the posted outcome counts. The registry reports the trial as completed, with enrollment of 26, and identifies hyperuricemia as the condition of interest. It does not report detailed baseline uric acid values or characterize how long participants had hyperuricemia.

3. Trial Design

This was a phase 2, randomized, parallel-group trial with quadruple masking, comparing rasburicase with placebo. The registry reports enrollment of 26 participants, with 13 participants in each reported outcome group. The sponsor was the University of Florida. The recorded start was 2008-10, primary completion was 2011-07, and status is completed.

The parallel design assigns participants to separate treatment groups, so the primary outcome is reported for the rasburicase group and the placebo group. Randomization is recorded, but the sequence-generation method, allocation concealment procedures, and details of implementation are not reported in the registry record. Quadruple masking is also recorded, but the specific roles of the masked parties and the procedures used to maintain masking are not reported. The registry therefore identifies key design features without giving enough detail to assess how they were implemented.

The planned clinical context was cardiovascular surgery, and the primary outcome timeframe was within 48 hours postoperatively. The registry describes the intervention as rasburicase to lower serum uric acid, but does not report the dose, administration schedule, treatment duration, or the timing of administration relative to surgery. Details about the surgical procedures, perioperative care, and criteria for enrollment beyond the condition of hyperuricemia are not reported.

The registry explicitly states that a power analysis could not be performed because no similar study had been performed. The investigators therefore describe the study as a pilot with 26 subjects and state that criteria were set to maximize the likelihood of seeing an effect. The particular criteria and any further design rationale are not reported. This description supports reading the study as a pilot rather than as a trial whose sample size was justified by a stated target effect and power calculation.

The posted results include one primary outcome measure and no posted secondary outcome measures. There are no analyses listed in the registry record. The primary outcome data and the reported comparison are available, but further information about analysis populations, covariate adjustment, handling of missing observations, or protocol deviations is not reported.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A large number of patients were screened to achieve the final participant numbers.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 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.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Acute Kidney Injury (AKI)., measured over Within 48 hours postoperatively.

The primary endpoint is the number of participants with acute kidney injury within 48 hours after surgery. The registry defines acute kidney injury as either an increase in serum creatinine of 0.3mg/dL from baseline or a 50% increase in serum creatinine from baseline values within that postoperative timeframe. The endpoint is reported as participant counts in the rasburicase and placebo groups.

Serum creatinine is used in the registry definition as the measure that identifies a postoperative change in kidney function. An endpoint with a defined threshold and timeframe gives the outcome a consistent operational meaning for the trial: participants either meet the stated criterion within the specified period or do not. This is a general explanation of how a binary endpoint works; it does not establish whether the threshold captures every clinically relevant form of kidney injury.

The registry describes the endpoint as acute kidney injury following cardiovascular surgery, matching the trial’s stated question about whether lowering serum uric acid before surgery would reduce its occurrence. The timeframe is important to interpretation: the posted endpoint concerns events within 48 hours postoperatively, not kidney outcomes across an unspecified longer follow-up period. The registry record does not report details about how serum creatinine was measured, how baseline values were chosen, how the two criteria were applied when both could be relevant, or whether outcome assessment was independently adjudicated.

The posted counts are 13 of 13 participants in each arm. This endpoint therefore records the same number of events in both groups. It does not, by itself, describe the severity or duration of acute kidney injury, later kidney function, renal replacement therapy, or mortality. Although the official title names those broader outcomes, the registry reports only one outcome measure, the primary acute kidney injury endpoint.

7. Results Posted in the Registry

• Rasburicase Group: 100.0% (13/13) versus 100.0% (13/13) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

A binary endpoint records whether each participant experienced a defined event. For this trial, the event is acute kidney injury within 48 hours postoperatively, according to the serum creatinine criteria in the registry. A count of participants with the event is reported for each arm. This form of outcome is different from a continuous measure, such as a laboratory value recorded on a scale, because the posted endpoint focuses on whether the specified threshold was met.

What the group counts describe

The rasburicase group is reported as 13 participants, with 13 participants meeting the primary endpoint. The placebo group is also reported as 13 participants, with 13 meeting the endpoint. Counts describe the observed participants and should be distinguished from estimates intended to generalize beyond them. The posted group counts are direct descriptive information; they do not, alone, provide a complete account of uncertainty about a treatment effect.

How to read a risk difference

A risk difference compares the proportion of participants with an event in one group with the corresponding proportion in another. In general, it expresses the contrast on an absolute scale. A value of 0.0 means the reported event proportions are the same under the calculation used. In this record, the posted risk difference is 0.0. The result is consistent with the equal event counts, but it remains an estimate based on the enrolled participants.

In general, absolute contrasts can be useful because they describe the size of a difference in event occurrence rather than expressing it as a multiple. The interpretation depends on the endpoint definition and the study population. Here, the endpoint is tied to the stated postoperative timeframe and serum creatinine criteria. The record does not report a treatment-effect threshold that would define a clinically important difference.

How to read a risk ratio

A risk ratio compares event risk in one group with event risk in another as a relative measure. A value of 1.0 indicates equal observed risks under that comparison. The registry reports a risk ratio of 1.0, and the posted limits are also 1.0. This is another way of expressing the same lack of observed separation in the event counts. Relative and absolute measures offer different scales for describing a contrast; neither should be mistaken for proof of equivalence.

What a p-value can and cannot say

A p-value evaluates how compatible the observed data are with a specified statistical model or null hypothesis. In general, a larger p-value does not prove that there is no effect, and a p-value is not the probability that a treatment works or fails. The registry reports p=1.0 for the comparison. This value accompanies equal counts, but does not answer whether a different study or population would produce a different result. The statistical test and its assumptions are not reported in the registry record.

Why over-dispersion matters in general

Over-dispersion is a general concern for some count outcomes when variation exceeds what a chosen model expects. It can affect uncertainty estimates and therefore the width of intervals or the behavior of tests. It is not a reason to reinterpret every binary endpoint as an over-dispersed count. The outcome is posted as participant counts for a binary event, and the registry does not report a model or an over-dispersion assessment. It would therefore be unsupported to claim that over-dispersion was present or that a particular adjustment was used.

What the confidence interval contributes

In general, a confidence interval gives a range of estimates compatible with a statistical procedure applied to the data. Its width reflects precision under the method and assumptions used. The registry reports a risk-difference interval of 0.0 to 0.0 and a risk-ratio estimate and limits of 1.0. Because the record does not describe the interval method, the stated limits should be reported as posted rather than treated as a complete account of uncertainty. The identical limits do not establish that the true effect is known without uncertainty.

Randomization is recorded as the allocation method. In general, random assignment is intended to support a fair comparison by reducing systematic differences between groups at assignment, but the registry record does not describe the randomization procedure or concealment. Quadruple masking is recorded, but the roles masked and procedures are not reported. Those design labels are relevant, but do not replace details about implementation.

The registry says a power analysis could not be performed because no similar study had been performed, and describes the trial as a pilot with 26 subjects. A sample-size planning illustration is conceptually different from an observed treatment result: it asks how many participants per arm might be needed under specified assumptions, rather than reporting what the trial observed. The described illustration assumes a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such an illustration is not observed power and does not supply the trial’s original sample-size justification. The registry itself says that the original power analysis could not be performed.

10. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimated treatment contrast. A confidence interval is commonly used to communicate that uncertainty: a narrower interval indicates a more concentrated range under the method used, while a wider interval allows a broader range. This is a general explanation; the interpretation depends on the procedure and assumptions used to construct the interval.

The registry reports the risk difference as 0.0, with both confidence limits at 0.0. It reports the risk ratio as 1.0, with both limits at 1.0. These intervals have no reported width. That is the numerical result in the registry record, but it should not be read as evidence that the treatment effect is known with perfect precision. The record does not report the interval calculation method, and the small pilot enrollment makes it especially important not to treat the posted limits as a definitive statement about uncertainty in a wider population.

The equal event counts explain why the reported point estimates show no contrast in this sample. They do not, on their own, tell readers how much variation could arise in other participants or settings. A confidence interval’s usefulness depends on an appropriate method and transparent reporting of that method. Neither the method nor its assumptions are described in the registry record. No alternative interval or adjusted estimate is reported.

There is also no reported sample-size justification based on a target effect and desired precision. Instead, the registry states that a power analysis could not be performed because no similar study had been performed and describes the work as a pilot. This limits how much can be inferred from the absence of a difference in the observed counts. The record does not report a prespecified equivalence margin or a precision target. Accordingly, the findings are best expressed as identical observed counts with the reported estimates and intervals, rather than as evidence that meaningful differences have been excluded.

11. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary outcome measure and no posted secondary outcome measures. No analyses are listed in the registry record. The official title names kidney function, renal replacement therapy, and all-cause mortality in addition to acute kidney injury, but the posted outcome results include only the acute kidney injury measure. Results for those other outcomes are not reported in the registry record.

Multiplicity arises in general when several outcomes, comparisons, or analyses are tested, because repeated testing can increase the chance of a seemingly notable result. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or a broader analysis plan. Because only one outcome measure is posted, it is not possible to determine from this record how the reported endpoint related to any planned but unreported analyses. The record does not say whether additional outcomes were planned, measured, or omitted.

Missing-data handling and analysis populations are also not reported. The outcome groups each include 13 participants, but those counts alone do not establish whether all randomized participants were analyzed as assigned, whether any participants withdrew, or whether any outcome data were unavailable. The registry does not report an intention-to-treat population, a per-protocol population, exclusions, protocol deviations, or imputation procedures. No assumptions about missing observations should be inferred from the equal group sizes.

The record also does not describe the statistical analysis plan, including the test used for the posted p-value, any adjustment for baseline characteristics, or whether analyses were prespecified. This absence does not invalidate the descriptive counts, but it limits the ability to assess how the comparison was selected and conducted. The reported result should therefore be read as the comparison recorded, with the scope of inference restricted by the lack of detail on multiplicity, missing data, and analysis populations.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The serious adverse event figures report 0 affected participants among 13 at risk in the rasburicase group and 0 among 13 at risk in the placebo group. The registry also reports 0 participants affected by other adverse events among 13 at risk in each group. These are the posted group-level counts.

Such counts describe events captured in the registry’s adverse-event reporting. They do not establish that no adverse events of any kind occurred, nor do they provide details about event definitions, collection procedures, severity grading, attribution, or follow-up duration. The registry’s list of top serious adverse event terms is empty. Death counts are not reported in the registry record.

Zero reported affected participants in each group means the registry has no events in these categories to compare in this record. With no reported events, these figures cannot show a difference between groups in observed event counts, and they do not establish equal underlying safety profiles. Interpretation is limited by the small numbers at risk and by the absence of additional reporting details. The adverse-event figures should also be kept separate from the primary acute kidney injury endpoint, which was reported as occurring in all 13 participants in each arm.

13. What the Result Does, and Does Not, Mean

The result means that the registry records acute kidney injury in 13 of 13 participants assigned to rasburicase and 13 of 13 assigned to placebo, within the primary endpoint’s postoperative timeframe and definition. The reported risk difference is 0.0, and the reported p-value is 1.0. In this sample, the event counts show no observed separation between groups.

That finding does not establish that rasburicase and placebo have identical effects. A pilot trial with 26 participants, described by its investigators as too early for a power analysis based on similar studies, cannot by itself settle the size or direction of an effect in a broader population. The registry reports intervals with identical limits, but does not give the method that produced them. Those limits should not be interpreted as proof that uncertainty is absent.

The posted data also do not show whether serum uric acid was lowered, because the registry does not report that outcome. They do not establish effects on kidney function beyond the acute kidney injury definition, renal replacement therapy, or all-cause mortality. Although these outcomes appear in the official title, they are not among the posted outcome measures. No secondary results are reported.

The safety counts record no serious or other adverse events among participants at risk in either group. They do not show that no adverse events occurred outside the registry’s reported categories or observation procedures. Death figures are not reported. The registry does not provide information needed to assess the completeness of adverse-event collection.

Overall, the appropriate conclusion is narrow: the posted primary outcome counts are identical, and the registry comparison reports no difference for this endpoint. The result is descriptive evidence from a small pilot, not a demonstration of equivalence, absence of effect, or conclusions about outcomes that were not reported. It also does not establish the clinical value of the proposed mechanism, since the record does not post the serum uric acid response or the detailed treatment protocol.

14. Why This Trial Matters Statistically

Statistically, this trial is notable for the contrast between a clear observed pattern and limited inferential detail. The primary endpoint counts are identical: 13 of 13 participants in each group met the acute kidney injury definition. The reported risk difference is 0.0 and the p-value is 1.0. These results are straightforward to describe, but they do not resolve whether a treatment effect exists beyond the enrolled participants.

The registry explicitly identifies the study as a pilot and states that a power analysis could not be performed because no similar study had been performed. That information matters because a pilot’s results can help describe feasibility or inform later work, but its observed estimates are not automatically precise or definitive. The record does not report specific feasibility outcomes, nor does it report how the findings were intended to guide a subsequent study.

The example also illustrates why uncertainty reporting matters. The posted confidence limits are identical, and the method used to produce them is not documented in the registry record. Readers need methods as well as estimates to judge what an interval communicates. The numerical output can be quoted accurately while remaining cautious about what it supports.

Finally, the title refers to several outcomes, while the posted results include only the primary acute kidney injury measure. Keeping the scope of the conclusion aligned with the scope of reported results is a core statistical discipline. This trial matters as an example of how to separate observed counts, reported comparisons, and unanswered questions without turning a null comparison into proof of no effect.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

This trial has a small reported enrollment of 26, with 13 participants in each outcome group. The registry describes it as a pilot and says a power analysis could not be performed because no similar study had been performed. This limits the ability to interpret the identical observed counts as ruling out potentially important differences.

Important design details are not reported, including eligibility criteria beyond the condition, randomization procedures, allocation concealment, masking implementation, treatment dose and schedule, and surgical characteristics. Participant baseline features and serum uric acid values are also not reported. Without those details, readers cannot assess the enrolled population’s clinical profile or the consistency of treatment and outcome measurement.

The primary endpoint has a defined serum creatinine threshold and a 48-hour postoperative timeframe, but measurement procedures and outcome adjudication are not reported. The registry gives confidence limits with identical endpoints but does not state the calculation method. It also does not report the statistical test, analysis plan, analysis populations, missing-data handling, or protocol deviations. These gaps constrain assessment of the comparison and its precision.

Only the primary acute kidney injury outcome is posted. Kidney function, renal replacement therapy, and all-cause mortality results are not reported in the registry record despite appearing in the official title. The registry also does not report serum uric acid response, and death counts are not reported in the adverse-event data. Consequently, conclusions should remain limited to the posted event counts, reported comparison, and adverse-event figures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lowering Serum Uric Acid to Prevent Acute Kidney Injury — NCT00756964.
• Registry record last updated 2012-09-03; status last verified 2012-08.
• Results first posted 2012-09-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed phase 2, randomized, quadruple-masked, parallel-group pilot trial sponsored by the University of Florida. It enrolled 26 participants and compared rasburicase with placebo. The primary outcome was acute kidney injury within 48 hours after surgery, defined by specified serum creatinine increases from baseline.

The posted primary outcome records 13 of 13 participants with acute kidney injury in each group. The reported risk difference is 0.0, with limits of 0.0 and 0.0; p=1.0. The registry reports a risk ratio of 1.0 with limits of 1.0. It reports no affected participants for serious or other adverse-event categories in either group; death figures are not reported.

The registry describes the study as a pilot and says a power analysis could not be performed because no similar study had been performed. No secondary outcomes or analyses are posted. The findings therefore describe the recorded primary outcome in this small trial and do not establish equivalence or address unreported outcomes.