Protocolized Diuretic Strategy in Cardiorenal Failure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Protocolized Diuretic Strategy in Cardiorenal Failure (NCT01921829), a randomized phase 4 study. The primary outcome is Change in Body Weight (kg) From Randomization to Day 4 or Date of Discharge (Whichever Comes First).

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group Phase 4 trial. Participants were allocated to Usual Care or the Protocolized Diuretic Strategy. The registry lists enrollment as 19 and trial status as terminated. The start and primary completion dates are recorded as 2013-11 and 2015-11. The reason for termination is not reported in the registry record.

The comparator was usual medical care with escalating diuretics and other therapy described as following heart-failure guidelines. Dosing in this arm was described as variable. The experimental strategy used an algorithm to adjust diuretics based on measured urine output, with a target of 3-5 L/day and stepped intensification. The registry’s arm descriptions are incomplete, so details beyond those statements are not reported in the registry record.

The endpoint results list 10 participants in Usual Care and 8 in the protocolized-strategy arm. The primary endpoint description explains that one participant assigned to the ProDiuS arm withdrew before undergoing randomized treatment. The registry does not report further details about allocation concealment, the identity of the masked party, or the analysis population used for the posted comparison.

The primary outcome was change in body weight from randomization to day 4 or discharge, whichever came first. Secondary outcomes included hospitalization duration, rehospitalizations, all-cause mortality, fluid balance, acute kidney injury, and other clinical and quality-of-life measures. The record lists 21 outcome measures and 20 analyses, while 19 secondary outcomes are posted. The available record does not establish why the study terminated or whether all planned outcomes were collected.

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: One participant was enrolled but withdrew consent before receiving any randomized treatment protocol. Therefore, that patient was withdrawn.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One patient from ProDiuS arm withdrew before undergoing any randomized treatment.

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 Change in Body Weight (kg) From Randomization to Day 4 or Date of Discharge (Whichever Comes First), measured over 4 days (96 hours).

The primary endpoint was change in body weight in kilograms from randomization to day 4 or the date of discharge, whichever came first. The registry defines change as the weight at that later time minus the baseline weight. Weights were taken in hospital on standard scales, without shoes and while wearing a hospital gown, before breakfast and after voiding.

Body weight is a continuous measure. In this study it was used to describe change during a short treatment period in participants with cardiorenal failure and edema. The registry’s rationale focuses on diuretic treatment and fluid removal, and the outcome therefore gives a measurable clinical indicator during the hospitalization. A negative change under the stated calculation means that the recorded later weight was lower than baseline; it does not, by itself, identify the cause of that change.

The endpoint window was not a uniform fixed visit for every participant: discharge could occur before day 4, and the earlier of those times was used. The posted arm summaries give means and standard deviations. Usual Care had a mean change of -2.07 kg with a standard deviation of 4.84; the protocolized-strategy arm had a mean change of -6.12 kg with a standard deviation of 1.95. The registry reports no confidence interval for the between-arm effect, and further details about endpoint missingness are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, because body-weight change can take values across a numerical scale. The registry summarizes each arm using a mean and standard deviation. A mean describes the center of the observed values; a standard deviation describes how dispersed those values are around that center. Neither statistic alone gives the uncertainty in the comparison between arms.

What does the reported t-test assess?

The registry reports a two-sided t-test. In general, a two-sample t-test evaluates whether the observed difference in group means is compatible with a null hypothesis of no difference, under the assumptions of the test. A two-sided test considers departures in either direction rather than only a prespecified direction. The reported p value is 0.05. It does not tell the reader the probability that the null is true, and it does not describe how large or important a difference is.

For a t-test, the validity of the reference calculation depends on assumptions about independent observations and the distribution of outcomes, as well as on the way variability is handled. The registry does not report diagnostic checks, a variance assumption, or any adjustment to the test. The arm sizes are small, so distributional features and individual values could have substantial influence; the posted summaries do not permit those features to be examined.

Why are confidence intervals useful?

A confidence interval gives a range of effect estimates compatible with the data under a specified statistical procedure. It communicates precision as well as direction and scale, which a p value alone does not. No confidence interval or comparative effect estimate is reported for the primary outcome. It is therefore not possible to use a posted interval to judge the range of plausible between-arm effects.

The posted arm summaries are not themselves an interval for the comparison. In particular, a standard deviation reflects participant-to-participant spread, while uncertainty about a mean or a difference in means also depends on sample size and the analysis method. General statistical interpretation should keep those quantities distinct.

What does recalculation mean?

A simple unadjusted recalculation from posted summary statistics can be useful as a check when the necessary inputs and a clearly defined comparison are available. It does not replace the sponsor’s analysis, which is the primary reported analysis. For this continuous two-arm endpoint, the registry record does not provide an estimable recalculated comparison in the posted results. No independent effect estimate or p value should be inferred from the arm summaries alone.

When a discrepancy between a sponsor analysis and a recalculation is identified, the sponsor’s own analysis takes precedence for reporting what the trial concluded. The record does not identify a discrepancy for this endpoint. The reported sponsor analysis is a two-sided t-test with p = 0.05, while the registry does not provide its comparative estimate or confidence interval.

How should planning calculations be read?

Sample-size planning illustrations are design calculations, not observed results and not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning output is expressed as participants per arm. Such illustrations describe hypothetical future planning under stated assumptions; they do not show that the completed trial had a particular probability of detecting an effect.

The registry does not report the trial’s own sample-size justification. The planning illustrations should not be mistaken for the enrollment target or for evidence that the study was adequately powered. The observed enrollment was 19, and the posted primary endpoint groups contain 10 and 8 participants.

Why does over-dispersion matter?

As a general concept, over-dispersion means that observed variability is greater than a statistical model assumes. When a model understates variability, its standard errors and uncertainty estimates may also be too small, which can make results appear more precise than they are. The primary outcome is analyzed as a continuous measure with a t-test, and the registry does not report an over-dispersion assessment. The concern is therefore a general statistical principle, not a finding established for this trial.

More broadly, the record does not report the detailed statistical analysis plan, interim analyses, missing-data procedures, or a formal multiplicity strategy. Those omissions limit assessment of how the reported p value fits into the full set of planned analyses. The posted result remains interpretable as the registry’s stated test, but important features of the analysis cannot be independently checked from the record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Usual Care", "Protocolized Diuretic Strategy")
n   <- c(10, 8)
m   <- c(-2.07, -6.12)
sp  <- c(4.84, 1.95)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Usual Care  10  -2.070  4.840  -5.532  1.392
CARM  Protocolized Diuretic Strategy  8  -6.120  1.950  -7.750  -4.490

11. Analyses Reported by the Sponsor

The registry’s reported comparison is a two-sided t-test with p = 0.05. The sponsor’s comparative effect estimate and confidence interval are not reported in the registry record. Although the arm means, standard deviations, and group sizes are posted, the primary continuous comparison is not available as an estimable unadjusted recalculation in the registry results. No recalculated effect or p value is therefore presented as a substitute.

The record does not identify a discrepancy between a sponsor analysis and a recalculation. The sponsor’s reported test is consequently the available inferential result for the primary endpoint. Its p value should be read alongside the arm summaries and the small group sizes, not as a measure of effect magnitude or precision. A confidence interval would provide information about the range of comparative effects compatible with the analysis, but none is reported.

The posted test does not resolve other questions about analysis populations, missing outcomes, or multiplicity. Those details are not reported in the registry record. The trial’s primary finding should therefore be described using the reported arm summaries and test, without attributing unreported methods or conclusions to the sponsor.

12. Multiplicity, Missing Data and Analysis Populations

The record lists 21 outcome measures, 20 analyses, and 19 posted secondary outcomes. The secondary outcomes cover several domains, including length of hospitalization, heart-failure and total rehospitalizations, all-cause mortality, fluid balance, acute kidney injury, a measure of right internal jugular vein area, and change in the Kansas City Cardiomyopathy Questionnaire clinical score at 1 month. The primary endpoint is change in body weight through day 4 or discharge, whichever comes first.

When many outcomes are tested, the chance of at least one apparently unusual result can increase if each is interpreted without accounting for the number of tests. General approaches to multiplicity include prespecifying a hierarchy or adjusting the testing procedure. Whether either approach was used is not reported in the registry record. No conclusion about adjustment should be inferred from the number of posted outcomes alone.

The primary endpoint description says one participant in the ProDiuS arm withdrew before undergoing randomized treatment. The endpoint group sizes are 10 for Usual Care and 8 for the protocolized strategy. The record does not describe the analysis population definition, the handling of the withdrawal, or whether other values were missing. It also does not report imputation procedures, sensitivity analyses for missing data, or a participant flow account sufficient to establish how every enrolled participant contributed to each analysis.

The registry does not report the trial’s sample-size justification, interim analyses, or a complete statistical analysis plan. These omissions matter because they leave uncertainty about the intended hierarchy of outcomes, planned stopping or monitoring procedures, and prespecified rules for analysis. The trial is listed as terminated, but the reason for termination is not reported in the registry record. Nothing in the posted information establishes whether termination affected the planned analyses or outcome collection.

13. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac arrhythmia (20.0%), hospitalization (20.0%), hospitalization for non-cardiac cause (10.0%).

The registry reports serious adverse events affecting 2 of 10 participants in Usual Care and 1 of 9 participants in the Protocolized Diuretic Strategy group. Other adverse events affected 7 of 10 and 2 of 9 participants, respectively. The deaths reported are 1 in Usual Care and 4 in the protocolized-strategy group. These are descriptive counts in a small trial and should not be treated as precise estimates of comparative risk.

The registry lists cardiac arrhythmia and hospitalization among the top serious adverse event terms, each recorded as 20.0%, and hospitalization for a non-cardiac cause as 10.0%. The record does not clarify whether participants could contribute to more than one term, how terms were selected for this listing, or whether events were considered related to treatment. Attribution and event timing are not reported in the registry record.

These safety figures should be read separately from the primary body-weight comparison. The counts do not establish why an event occurred, and the number of deaths alone does not establish a treatment effect. With the available record, the appropriate interpretation is a description of the recorded event counts, not a causal conclusion.

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

The posted data describe a small randomized trial comparing usual care with a protocolized diuretic strategy in cardiorenal failure. For the primary endpoint, both arm means show a decrease in body weight under the registry’s calculation. The mean change was -2.07 kg in Usual Care and -6.12 kg in the protocolized-strategy arm. The reported two-sided t-test p value was 0.05.

These summaries do not establish the size or precision of a comparative treatment effect. The registry does not report a confidence interval or comparative effect estimate, and the endpoint groups contain 10 and 8 participants. The p value does not show that a treatment effect is certain, nor does it measure clinical importance. The means and standard deviations describe the observed groups; they cannot by themselves establish how the result would generalize beyond the participants studied.

The trial record also includes multiple secondary outcomes and safety counts. Their presence does not establish that every outcome was collected or analyzed according to a prespecified plan. Multiplicity handling, missing-data methods, the analysis population, and the reason for termination are not reported in the registry record. The serious adverse event and mortality counts are descriptive and cannot, on their own, establish causation.

The appropriate conclusion is limited to what the registry reports: the trial was randomized, enrolled 19 participants, and posted the stated arm summaries and t-test for the primary weight-change endpoint. This result does not by itself prove that the strategy improves clinical outcomes, nor does it establish that it has no effect. Greater certainty would require a fuller account of the analysis and more precise evidence than is available in this record.

15. Why This Trial Matters Statistically

This trial raises a useful statistical question: how should readers interpret a randomized comparison when the endpoint summaries are available but the comparative estimate and its confidence interval are not? The arm means and standard deviations provide a descriptive account of observed changes, while the reported p value supplies a test result. Neither replaces a direct estimate of the between-arm effect with an interval showing its precision.

The small group sizes also make the distinction between observed data and broader inference especially important. Individual observations can have substantial influence in a small study, and the posted summaries do not show the distribution of values. Statistical assumptions and sensitivity to those values cannot be assessed from the means and standard deviations alone.

The record offers a further lesson about completeness. It lists many outcome measures and analyses, but does not report a multiplicity strategy, missing-data procedures, the analysis population, or a full statistical plan. Those details help readers understand how a single p value relates to the full set of planned analyses and how participants with unavailable outcomes were handled.

Finally, planning illustrations based on an observed effect are not evidence of observed power, and they are not the trial’s original sample-size justification. Keeping design calculations separate from completed-trial results helps prevent a hypothetical planning scenario from being mistaken for what the study established. Taken together, these issues make the registry a case in careful interpretation: state the results precisely, distinguish description from inference, and acknowledge what the record does not report.

16. 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 enrollment was 19, and the posted primary endpoint groups contain 10 participants in Usual Care and 8 in the protocolized-strategy arm. The endpoint description notes that one participant assigned to the protocolized arm withdrew before receiving randomized treatment. The record does not explain how this participant was handled in the primary analysis or whether other outcome data were missing.

The registry reports group means, standard deviations, and a two-sided t-test p value, but no comparative effect estimate or confidence interval. This limits assessment of the estimated contrast and its precision. The small groups also limit what can be learned about the distribution of outcomes and the stability of the summaries.

The trial is listed as terminated, but the reason is not reported in the registry record. Further details about the allocation process, the masked party, the statistical analysis plan, interim analyses, multiplicity adjustment, and the analysis population are also not reported. The arm descriptions are incomplete, limiting assessment of the exact treatment procedures and comparator care.

The registry lists many secondary outcomes, but the relationship between those analyses and the primary endpoint is unclear because a multiplicity approach is not reported. Safety counts are descriptive; event attribution and timing are not reported. These limitations mean that the available results should be interpreted as a record of the posted summaries and test, without assuming unreported methods or making causal claims beyond the trial data.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Protocolized Diuretic Strategy in Cardiorenal Failure — NCT01921829.
• Registry record last updated 2017-08-21; status last verified 2017-07.
• Results first posted 2017-07-17.
• 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.

20. Record Summary

NCT01921829 is a randomized, single-masked, parallel-group Phase 4 trial of a Protocolized Diuretic Strategy versus Usual Care in cardiorenal failure. The registry lists enrollment of 19 and trial status as terminated. The primary endpoint was change in body weight from randomization to day 4 or discharge, whichever came first.

For this endpoint, Usual Care had a mean change of -2.07 kg with a standard deviation of 4.84 among 10 participants. The protocolized-strategy arm had a mean change of -6.12 kg with a standard deviation of 1.95 among 8 participants. The registry reports a two-sided t-test p value of 0.05, without a comparative effect estimate or confidence interval.

The record also lists secondary outcomes and adverse event counts. Details of missing-data handling, multiplicity, the analysis population, the reason for termination, and several statistical procedures are not reported in the registry record. The findings are best understood as descriptive and inferential results from a small trial with important reporting limitations.