Restrictive Fluid Therapy in Severe Preeclampsia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Restrictive Fluid Therapy in Severe Preeclampsia (NCT02214186), a randomized na study. The primary outcome is Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy.

2. Clinical Question

The trial also set out to assess cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) as markers of possible renal injury. Other registered outcomes concerned proteinuria, platelets, and coagulation measures. These additional measures broaden the clinical questions beyond creatinine, but their numerical results and comparative estimates are not reported in the registry record.

The registry describes the study hypothesis as that intraoperative fluid restriction did not influence renal function in this setting. That statement is the investigators’ stated hypothesis, not a result. Assessing the question statistically would require the observed creatinine values or a clearly defined between-group estimate, together with information about its precision. Those numerical details are not reported in the registry record, so the direction and size of any difference cannot be characterized from the available record.

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. It lists an enrollment of 46 and a status of completed. The study dates are recorded as starting in 2014-01 and reaching primary completion in 2015-03. The phase is listed as NA. The sponsor is University of Sao Paulo General Hospital.

The two treatment strategies differed in the amount of crystalloid administered during cesarean section. The restrictive group was assigned 250 mL, while the liberal group was assigned 1500 mL. The registry describes the liberal strategy as the non-intervention arm because that amount was usually used during cesarean section at the study setting. Both groups were undergoing cesarean section under spinal anesthesia in the setting of severe preeclampsia.

Random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline factors. That general property does not guarantee that groups in a particular trial are identical, and the registry entries needed to assess the allocation process are not reported in the registry record. With no masking, participants and relevant study personnel may have known the assigned fluid strategy; how that knowledge affected care, outcome assessment, or reporting is not described in the registry record.

The primary measure was creatinine, assessed preoperatively and on the first and second postoperative days. The registry lists nine outcome measures and nine analyses, but it does not report a single numerical primary comparison in the information available for this analysis. Details of the randomization procedure, allocation concealment, and statistical analysis plan are not reported in the registry record.

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: We calculated the total sample size from a pilot study. Assuming a power of 80% and 95% confidence, the sample necessary to conduct the study was 21 patients in each group of interest. As we considered 10% as maximum margin of loss during follow-up, there were 23 patients enrolled in each group.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Were included in the analysis the patients who violated the protocol and lost follow-up (intention to treat analysis)

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 Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy, measured over preoperative, first and second day postoperative.

The primary endpoint was renal function evaluated through creatinine levels, with the unit recorded as mg/dl. Measurements were scheduled preoperatively and on the first and second postoperative days. The registry describes the summary parameter as the median and the dispersion as the inter-quartile range.

Creatinine is a laboratory measure used in assessing kidney function. In general, a measurement taken before treatment can help describe the starting status, while postoperative measurements can describe kidney-related laboratory values after the procedure. Repeated measurements can also show whether the pattern differs over time between treatment groups. These are general reasons to collect the measure; they do not establish what happened in this trial.

The registry does not report the creatinine medians, inter-quartile ranges, changes over time, or a numerical comparison between groups. It also does not specify a single time point as the sole primary contrast in the information. Because there are multiple scheduled measurements, interpretation depends on the treatment contrast and time-point analysis actually used. That analytic detail is not reported in the registry record. Without the numerical results and the analysis definition, the size, direction, and precision of the primary outcome cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized and parallel-group. In general, random allocation is used to reduce systematic differences between groups at the time of assignment. A parallel design follows the assigned groups separately, rather than exposing each participant to both strategies in sequence. These design features help frame a comparison, but they do not by themselves supply the results or establish that all sources of bias were controlled.

What does a median and inter-quartile range describe?

The registry specifies the median as the summary measure for creatinine and the inter-quartile range as its dispersion. In general, the median is the middle value after observations are ordered. It can be useful when measurements are skewed or contain extreme values because it is less affected by those values than the arithmetic mean. The inter-quartile range describes the spread of the middle portion of the observations. Together, these summaries give a sense of a typical value and variability without requiring a symmetric distribution.

These descriptive summaries do not, by themselves, quantify the treatment effect. A comparison might be expressed as a difference between group summaries, a model-based contrast, or another estimand. The registry record does not report which comparative statistic was used for the primary outcome. It also does not report the values needed to reproduce or interpret a comparison.

Why are measurements at several times important?

Creatinine was scheduled preoperatively and on the first and second postoperative days. Repeated measurements can describe both the starting values and the subsequent pattern. A statistical analysis might compare groups separately at each scheduled time, examine change from baseline, or model the overall pattern. These approaches answer related but not identical questions. The registry record does not report which approach was used, whether baseline values were adjusted for, or whether a single time point was designated as the principal comparison.

In general, repeated observations on the same participant are related rather than independent. An analysis that accounts for that relationship can differ from one that treats each measurement as unrelated. The statistical model, assumptions, and handling of within-participant correlation are not reported in the registry record, so the analysis cannot be evaluated on those points.

What would an estimate and confidence interval add?

An effect estimate would describe the observed contrast between the strategies on a defined scale. A confidence interval would communicate the estimate’s uncertainty and the range of effects compatible with the data under the method’s assumptions. General statistical interpretation considers both the direction and magnitude of the estimate, its precision, and the clinical context. A p-value alone, even if available, would not convey the size of an effect or establish that an effect is absent. In this record, the primary estimate, interval, and p-value are not reported.

What does the record say about statistical planning?

The registry record does not report the sample-size justification, target effect, or statistical analysis plan. It also does not report whether interim analyses were planned or conducted. Those omissions mean the enrollment cannot be assessed against a stated power calculation, and the analysis choices cannot be checked against a prespecified plan. No claim about observed power can be made from enrollment alone. In general, post hoc power calculations based on an observed effect do not substitute for interpreting the estimate and its uncertainty.

How should additional outcomes be considered?

The registry lists nine outcome measures and nine analyses. Its listed secondary outcomes include NGAL, cystatin C, proteinuria, platelets, international normalized ratio of prothrombin time, and activated partial thromboplastin time. Multiple outcomes or repeated time-point comparisons can create a multiplicity issue: the more statistical tests considered, the more opportunities there may be to find a nominally unusual result by chance. General approaches include prespecifying a primary contrast, using a multiplicity adjustment, or treating secondary analyses as exploratory. The registry record does not report whether any such approach was used.

These general concepts explain what would be needed to interpret the statistical evidence; they do not imply that a particular method was applied in this trial. The record does not provide the numerical outcome summaries or comparative analyses needed to evaluate the primary endpoint, the secondary outcomes, or the assumptions behind any statistical tests.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures and nine analyses, with a primary creatinine outcome assessed at preoperative and postoperative time points and several secondary outcomes. When many outcomes or time-point comparisons are examined, the chance of at least one apparently notable finding can increase. This is the general multiplicity concern. It can be addressed in different ways, including defining a primary contrast in advance, adjusting for multiple comparisons, or interpreting secondary findings as exploratory. The registry record does not report a multiplicity strategy, hierarchy of outcomes, or the statistical analysis plan.

The primary outcome description identifies the analysis population as including patients who violated the protocol and those lost to follow-up, and labels the analysis intention to treat. This wording is not enough to establish exactly how missing observations were handled or whether every randomized participant was included in each outcome analysis. The registry record does not report the number of missing creatinine measurements, reasons for missingness, imputation methods, or sensitivity analyses. It therefore is not possible to assess the potential influence of missing data on the primary comparison.

In general, intention-to-treat analysis aims to analyze participants according to their randomized assignment, regardless of adherence, and can preserve the advantages of randomization. However, the registry’s brief population description does not clarify the analytic dataset or the treatment of participants without outcome measurements. Details of protocol deviations and follow-up are not reported in the registry record.

11. 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 registry reports zero serious adverse events among 21 participants at risk in the liberal fluid therapy group and zero among 21 at risk in the restrictive fluid therapy group. It also reports zero other adverse events among 21 at risk in each group. The death counts are null and are therefore not reported in the registry record.

These are event counts as recorded, not evidence that the underlying risk is zero. With no events recorded, the data do not provide an observed event rate above zero in these entries, but the absence of recorded events does not rule out events or risk beyond the observed participants and follow-up. A comparative safety estimate and its precision are not reported in the registry record.

The registry lists an enrollment of 46, while the adverse-event entries show 21 at risk in each group. The record does not explain how the safety populations relate to the enrollment figure, or provide further detail on safety follow-up and event ascertainment. The counts should therefore be read as the posted adverse-event figures, without assuming additional information about who was included or how long they were observed.

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

The registry record describes a randomized comparison of restrictive and liberal fluid strategies during cesarean section under spinal anesthesia among women with severe preeclampsia. It identifies creatinine as the primary renal-function measure and gives a measurement schedule spanning the preoperative period and the first and second postoperative days. It also describes the assigned crystalloid amounts and lists several additional laboratory outcomes.

What the record does not report is the numerical primary-outcome result. The creatinine summaries, between-group estimate, confidence interval, and p-value are not reported in the registry record. As a result, the record cannot establish the direction or size of any observed difference, how precisely it was estimated, or whether the results were compatible with a range of potentially important effects. The investigators’ hypothesis about no influence is not a finding and should not be read as confirmation of equivalence.

The posted adverse-event counts are zero in the serious and other event categories for the at-risk participants listed in each group. These observations describe the recorded events; they do not establish that either strategy has no risk. Death counts are not reported in the registry record, and safety follow-up details are not reported.

Consequently, the available information supports a description of the trial question and selected design features, but it does not support a conclusion about comparative renal function or the secondary outcomes. This is a limitation of what is reported in the registry record, not evidence that an effect was absent or present. Numerical results and sufficient analysis details would be needed for a statistical assessment of the treatment comparison.

13. Why This Trial Matters Statistically

This trial addresses a question where fluid administration and renal laboratory measures were central to the comparison: whether a restrictive strategy during cesarean section under spinal anesthesia was associated with a different creatinine pattern from a liberal strategy in severe preeclampsia. The randomized design is statistically relevant because random assignment can reduce systematic baseline differences on average. The absence of masking and the repeated outcome schedule are also important features when judging how results would be interpreted.

The endpoint is not a single measurement alone. Creatinine was scheduled before surgery and on the first and second postoperative days, so an analysis needs to make clear whether it concerns a particular time point, change over time, or an overall trajectory. Those choices define the treatment effect being estimated. The registry record does not report which comparison was used, underscoring why an endpoint description and numerical results must be read together.

The study also registered multiple secondary laboratory outcomes. Considering several measurements can provide a broader account of the clinical question, but it raises the general need to distinguish a prespecified primary inference from exploratory findings and to address multiplicity. The statistical plan and any adjustment are not reported in the registry record.

Most importantly, statistical interpretation depends on estimates and their precision, not simply on a stated hypothesis or a completed status. Because the registry record does not report numerical renal-function results, readers cannot assess the size of the estimated effect or the uncertainty around it. The record is therefore useful for understanding the planned comparison and the limits of the available evidence, while not allowing a substantive conclusion about the primary outcome.

14. 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.

The central limitation for interpretation is that numerical results for the primary creatinine endpoint are not reported in the registry record. The record gives the measurement schedule and summary format, but not the values, between-group contrast, confidence interval, or p-value. Numerical results for the listed secondary outcomes are also not reported in the information available for this analysis.

The record does not report the statistical analysis plan, the exact primary contrast, whether baseline creatinine was incorporated into the analysis, or how repeated measurements were handled. It also does not report a sample-size justification, interim analyses, or multiplicity procedures. These omissions prevent assessment of whether the analysis was prespecified and whether its assumptions and uncertainty were adequately addressed.

Masking is listed as none. The registry record does not explain how outcome assessment was conducted or whether laboratory measurements were interpreted without knowledge of assignment. Allocation concealment and the randomization procedure are not reported. The record also does not describe protocol deviations in detail or explain precisely how missing outcome measurements were handled. Its statement about including protocol violations and loss to follow-up in an intention-to-treat analysis leaves those operational details unresolved.

Safety entries report event counts and at-risk counts, but the relationship between those safety populations and the enrollment figure, the duration of safety follow-up, and event ascertainment procedures are not reported in the registry record. Death counts are not reported. These gaps limit assessment of both efficacy and safety; they should not be mistaken for evidence of no treatment effect or no risk.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Restrictive Fluid Therapy in Severe Preeclampsia — NCT02214186.
• Registry record last updated 2017-03-07; status last verified 2014-07.
• Results first posted 2015-09-07.
• 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.

18. Record Summary

The registry record describes a completed, randomized, parallel-group trial with no masking, sponsored by University of Sao Paulo General Hospital. Enrollment is listed as 46, with study start recorded as 2014-01 and primary completion as 2015-03. The population was women with severe preeclampsia undergoing cesarean section under spinal anesthesia.

The comparison was restrictive fluid therapy, described as 250 mL of crystalloid, versus liberal fluid therapy, described as 1500 mL. The primary endpoint was creatinine-based renal function assessed preoperatively and on the first and second postoperative days, summarized using medians and inter-quartile ranges. Additional registered outcomes included renal markers, proteinuria, platelets, and coagulation measures.

Numerical primary and secondary outcome results are not reported in the registry record. Serious and other adverse-event counts are listed as zero among 21 participants at risk in each group; deaths are not reported. The available record defines the clinical comparison but does not permit assessment of the size or precision of its renal-function findings.