Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network (ROSE) Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network (ROSE) Study (NCT01132846), a randomized phase 2 study. The primary outcome is Change in Cystatin C.

2. Clinical Question

The central question is therefore about a short-term laboratory measure in people hospitalized with acute heart failure and kidney dysfunction, rather than a direct measure of longer-term clinical outcomes. The registry describes the study as examining benefits and safety, but the posted primary endpoint is specifically a safety endpoint based on cystatin C change. The secondary outcomes include symptoms, weight, clinical stability, heart-failure status, and other measures. Those outcomes add context, but they do not change what the primary endpoint measures. The registry record does not report a formal hypothesis statement or a detailed definition of the population included in the primary analysis.

3. Trial Design

ROSE is listed as a phase 2, randomized, quadruple-masked, parallel-group study sponsored by Duke University. Its status is completed, and the registry lists enrollment of 360. The study began in 2010-08, with primary completion in 2013-05. These record details describe the registered trial, not the number included in each particular analysis.

The intervention structure included low-dose dopamine, low-dose nesiritide, and placebo. The arm descriptions state that active treatment or placebo was administered during the first 72 hours. The primary endpoint timeframe runs from randomization to 72 hours, so the posted primary comparison concerns an early change during the treatment period. The registry record does not report the randomization ratio, sequence-generation method, allocation concealment procedure, or the specific roles masked under quadruple masking.

The registry reports primary cystatin C data for 122 participants in the low-dose dopamine group, 119 in the placebo group, and 119 in the low-dose nesiritide group. These are the group counts associated with the posted primary endpoint; they should not be treated as counts for every secondary analysis. Counts differ for some secondary outcomes, and the registry record does not explain why.

The study also included a dyspnea substudy in a subset of participants. Its stated purpose was to assess whether the Provocative Dyspnea Severity Score was a more sensitive index of variability in clinical status than a dyspnea visual analog scale assessed without standardized conditions. The registry record does not provide a detailed substudy analysis plan or numerical results for that comparison.

The trial’s original sample-size justification, intended allocation proportions, and detailed statistical analysis plan are not reported in the registry record. The sample-size illustrations associated with the posted effect estimates are retrospective planning calculations, not evidence of the assumptions used to design or conduct the trial.

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.

Overall Study

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 Cystatin C, measured over Randomization to 72 hours.

The primary endpoint is the mean change in serum cystatin C, measured in mg/L, from randomization to 72 hours. Cystatin C is a laboratory measure; the registry labels this endpoint as the primary safety endpoint. The reported summary is a mean with standard deviation, so the posted arm values describe average changes and the variability of individual measurements around those averages.

A change score compares a measurement at the end of the stated interval with the measurement at its start. It therefore focuses on change over the trial’s early treatment period rather than on the absolute cystatin C value at a single time. Comparing average change between a treatment group and placebo can indicate whether the groups’ observed changes differ, while uncertainty estimates help show how precisely that difference is estimated.

For the primary endpoint, the registry reports a mean change of 0.12 in the low-dose dopamine group, 0.11 in the placebo group, and 0.07 in the low-dose nesiritide group. The posted unadjusted mean differences versus placebo are 0.01 mg/L for dopamine and -0.04 mg/L for nesiritide. These are short-term group averages, not individual predictions. The registry record does not report the clinical interpretation threshold for cystatin C change or a more detailed rationale for selecting this measure beyond identifying it as the primary safety endpoint.

7. Results Posted in the Registry

• Low Dose Dopamine: mean 0.12 versus 0.11 on control; difference 0.01 (95% CI -0.06 to 0.08), standardized effect d = 0.03; z-test p = 0.793.
• Low Dose Nesiritide: mean 0.07 versus 0.11 on control; difference -0.04 (95% CI -0.12 to 0.04), standardized effect d = -0.13; z-test p = 0.315.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in Weight

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Low Dose Dopamine: mean -7.40 versus -7.73 on control; difference 0.33 (95% CI -1.56 to 2.22), standardized effect d = 0.04; z-test p = 0.733.
  • Low Dose Nesiritide: mean -7.15 versus -7.73 on control; difference 0.58 (95% CI -1.31 to 2.47), standardized effect d = 0.08; z-test p = 0.547.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low Dose Dopamine and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low Dose Nesiritide and the control. The interval gives the range of effects that remain compatible with the data.

Worst Reported Symptom Changes-RED-ROSE

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Low Dose Dopamine: mean 20.90 versus 19.60 on control; difference 1.30 (95% CI -7.52 to 10.12), standardized effect d = 0.05; z-test p = 0.773.
  • Low Dose Nesiritide: mean 25.60 versus 19.60 on control; difference 6.00 (95% CI -1.92 to 13.92), standardized effect d = 0.25; z-test p = 0.138.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low Dose Dopamine and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low Dose Nesiritide and the control. The interval gives the range of effects that remain compatible with the data.

Change in Clinical Stability- RED-ROSE

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Low Dose Dopamine: 39.5% (30/76) versus 45.3% (34/75) on control; risk difference -5.9 percentage points (95% CI -21.6 to 9.9), risk ratio 0.87 (0.60–1.26); unadjusted two-proportion z-test p = 0.466.
  • Low Dose Nesiritide: 35.5% (27/76) versus 45.3% (34/75) on control; risk difference -9.8 percentage points (95% CI -25.4 to 5.8), risk ratio 0.78 (0.53–1.16); unadjusted two-proportion z-test p = 0.219.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low Dose Dopamine and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low Dose Nesiritide and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results cover several different kinds of outcomes, including continuous measures and a binary clinical-stability outcome. Their timeframes and analysis counts differ, so the results do not represent a single uniform assessment of treatment effects. The registry record lists additional secondary outcomes, but numerical summaries are not present for every outcome named in the record.

Across the secondary comparisons with numerical estimates, the pattern does not provide a clear, consistent separation of either active-treatment group from placebo. The recalculated intervals for the posted comparisons include the relevant null value. This broadly resembles the uncertainty in the primary cystatin C comparisons, but the secondary outcomes address different clinical or measurement questions and should not be treated as replications of the primary endpoint.

The secondary findings can add context about symptoms, weight, or clinical status, but they do not replace the primary safety measure. Differences among outcome definitions, timeframes, and analysis populations make it inappropriate to combine them into a single overall conclusion. The registry record does not report a prespecified hierarchy showing which secondary outcomes were intended to carry the greatest confirmatory weight.

Unadjusted secondary results carry less weight because multiple outcomes and treatment contrasts create many opportunities for chance findings. Without a reported multiplicity plan, an isolated nominal result would be difficult to distinguish from a chance finding. Conversely, a lack of a small p-value for a secondary endpoint does not establish absence of a potentially meaningful effect. The estimates and their precision, the outcome’s role, and the analysis plan all matter. Here, the registry record does not report adjusted secondary analyses or detailed analysis methods, so the secondary results are best treated as descriptive and exploratory.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Weight
• Worst Reported Symptom Changes-RED-ROSE
• Change in Clinical Stability- RED-ROSE
• Change in Serum Creatinine
• Dyspnea Visual Analog Scale Area Under the Curve
• Change in Heart Failure Status
• Change in Treatment Response
• Cumulative Urinary Sodium Excretion

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it is a measured quantity summarized by a mean and standard deviation. For each arm, the mean describes the average change in cystatin C, while the standard deviation describes how dispersed participant-level changes are around that average. A standard deviation is not the uncertainty in the arm mean; it describes variation among measurements.

What does a mean difference represent?

The mean difference compares an active-treatment group’s average change with the placebo group’s average change. A positive value means the treatment-group change is higher than the placebo-group change on the recorded scale; a negative value means it is lower. For dopamine, the posted difference is 0.01 mg/L. For nesiritide, it is -0.04 mg/L. These are unadjusted comparisons derived from the posted summaries, not adjusted estimates from a reported model.

How should the confidence intervals be read?

A confidence interval expresses uncertainty around an estimated difference. Narrower intervals indicate greater precision, while wider intervals indicate less precision. For a difference, an interval that spans zero is compatible with no difference as well as with differences in either direction within the interval. Both primary intervals span zero. This does not prove the true difference is zero; it indicates that the data do not pin down the difference precisely enough to exclude zero under this calculation.

What does a p-value add?

A p-value summarizes how compatible the observed data are with a specified null hypothesis under the assumptions of the test. The posted primary values are p = 0.793 for dopamine versus placebo and p = 0.315 for nesiritide versus placebo. These are unadjusted p-values. They are not the probability that the null hypothesis is true, nor do they measure the clinical importance of an estimated difference. The registry record does not report a sponsor analysis for these comparisons, a testing hierarchy, or an adjustment for multiple comparisons.

Why does variability matter?

When participant measurements vary widely, the group means are estimated less precisely unless the data include enough information to offset that variation. The primary endpoint standard deviations are 0.32 for dopamine, 0.27 for placebo, and 0.34 for nesiritide. The observed group sizes and variability jointly inform the precision of the comparisons. A mean difference alone gives no complete account of that uncertainty, which is why the interval estimates matter alongside the point estimates.

What is meant by an unadjusted recalculation?

The posted comparison estimates are simple, unadjusted recalculations from arm-level means and standard deviations. They do not incorporate covariate adjustment, stratification, repeated-measures modeling, or any other approach unless that information is stated in the registry record. Such methods may be used in a trial’s full analysis, but the registry record does not report them. The record also does not report how missing measurements were handled or which analysis population was specified.

The results are listed for each active group against placebo, rather than as a single overall test across all three arms. Two separate comparisons create more than one opportunity for a result to appear unusual by chance. When many outcomes and contrasts are examined, multiplicity becomes relevant: a planned adjustment or a prespecified hierarchy can help define how to interpret the collection of tests. Neither is reported in the registry record, so the listed p-values should not be treated as multiplicity-adjusted evidence.

There are important limits to what can be inferred from summary statistics. Group means and standard deviations do not show the shape of the participant-level distribution, whether it contains outliers, or whether changes differ across subgroups. The registry record does not report participant-level data, diagnostic checks, or the detailed analysis model. The recalculations therefore provide a transparent comparison of the posted summaries, but they cannot reproduce every possible analysis of the trial data.

11. Confidence Intervals and Precision

The primary comparison estimates are close to zero, but their confidence intervals span zero. This means the posted summaries are compatible with no mean difference and also with differences in either direction within the respective intervals. The interval for dopamine versus placebo is reported as -0.065 to 0.085 mg/L; the interval for nesiritide versus placebo is reported as -0.118 to 0.038 mg/L. These ranges are uncertainty summaries, not forecasts of individual participant changes.

Precision depends on both the amount of information and the variation in measurements. The primary group standard deviations are 0.32, 0.27, and 0.34 mg/L. The group counts for this endpoint are 122 for dopamine, 119 for placebo, and 119 for nesiritide. The registry record does not report a target precision or a clinically important difference against which to judge whether these intervals are sufficiently narrow.

Because zero lies within both intervals, the posted comparisons do not rule out no difference. At the same time, the intervals include nonzero values, so the results do not prove that the true differences are exactly zero. Whether any value in the interval would matter clinically cannot be determined from the registry record, which does not state an interpretive threshold for cystatin C change.

Precision is distinct from statistical significance and from clinical importance. A p-value alone does not communicate the full range of compatible effects, and a confidence interval alone does not identify which differences would matter to patients or clinicians. The primary summaries should therefore be read together: the group means, estimated contrasts, p-values, and intervals all describe different aspects of the evidence.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on the observed effect, rather than the trial’s original design assumptions. For continuous outcomes, the figures are participants per arm, not total participants. The stated calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original design’s own sample-size assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm estimated to be needed for an 80% chance of detecting the specified effect under those planning assumptions, if that effect were the true effect. The 90% power column uses a higher target chance of detection and therefore requires more participants per arm for the same assumed effect. These are conditional planning quantities, not guarantees that a future study will detect a difference.

The rows use 100%, 75%, and 50% of the observed effect. A smaller effect is harder to distinguish from random variation, so the planning calculation requires more participants per arm as the assumed effect becomes smaller. The estimates can rise sharply when the observed effect is small, as is relevant to interpreting calculations built from modest differences in this trial.

This is not observed power. It is a retrospective planning illustration using the observed effect estimate, and it does not tell whether the completed trial was adequately designed or whether its result is true. The illustrations also do not account for any design features or analysis methods not included in the stated assumptions. They should be read as conditional comparisons of planning scenarios, not as a substitute for the trial’s unreported original rationale.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.010; pooled standard deviation σ = 0.296.
2. n = 2 × (1.96 + 0.842)² × 0.296² / 0.010² = 13,788.2, rounded up to 13,789 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.01                      # observed difference in means
sigma <- 0.296369948617458                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1132846)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 13,789 (80% power), 18,459 (90% power)
 75% of observed effect: n per arm = 24,513 (80% power), 32,815 (90% power)
 50% of observed effect: n per arm = 55,153 (80% power), 73,834 (90% power)
power.t.test: 13789.1 
Simulated power at n = 13,789 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity adjustment, a testing hierarchy, or a detailed statistical analysis plan for the primary and secondary outcomes. The record lists one primary endpoint and multiple secondary outcomes, with separate comparisons of each active-treatment group against placebo. When several outcomes and contrasts are examined, the chance of at least one apparently unusual result can increase. An adjustment or prespecified hierarchy can address that issue, but no such approach is described in the registry record.

The recalculated p-values are unadjusted. They should not be read as if they account for all outcomes, timeframes, and contrasts in the trial. The registry record lists no reported analyses for the posted outcomes, so it is not possible from this record to determine whether the complete trial report used a different inferential approach or how the analyses were prioritized.

Missing-data methods are not reported in the registry record. The record also does not state whether the primary analysis used an intention-to-treat population, a modified intention-to-treat population, a per-protocol population, or another analysis set. Counts associated with different outcomes vary, but the record does not explain whether this reflects missing measurements, outcome-specific eligibility, or another reason. The counts alone cannot establish how missing data were handled.

The registry record does not report imputation methods, assumptions about missingness, sensitivity analyses, or rules for excluding observations. These omissions matter because different approaches to incomplete outcome data can affect estimates and uncertainty. Without those details, the posted summaries can be described, but the robustness of the estimates to missingness and analytic choices cannot be assessed.

These are reporting limitations in the registry record. They do not establish that the trial lacked a statistical plan or that data were missing in a particular way. They mean that those details cannot be evaluated from the registry record.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: hypotension (5.9%), sepsis (3.3%), renal failure (2.5%), anemia (1.7%), cardiac arrest (1.7%).

The registry reports serious adverse events for each group as counts alongside the number at risk: 30 of 122 for low-dose dopamine, 24 of 119 for placebo, and 21 of 119 for low-dose nesiritide. These are posted group counts, not adjusted comparisons. The registry record does not report a statistical comparison of serious adverse events or establish whether events were judged related to treatment.

The listed serious-event terms include Hypotension at 5.9%, Sepsis at 3.3%, Renal Failure at 2.5%, Anemia at 1.7%, Cardiac Arrest at 1.7%, and Ventricular Arrhythmia at 1.7%. The record does not specify in this summary whether these terms are broken down by treatment group, so they should not be assigned to individual arms.

The posted count for other adverse events is 0 in each group. Death counts are not reported in the registry record. A group count does not by itself describe event timing, severity distribution, recurrence, or causal attribution. These figures offer a registry-level description of reported events, not a complete safety analysis.

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

The results describe short-term changes in a laboratory measure and a set of secondary outcomes in a randomized study of acute heart failure with kidney dysfunction. For the primary cystatin C endpoint, the mean changes were 0.12 with dopamine, 0.11 with placebo, and 0.07 with nesiritide. The unadjusted differences versus placebo are small in the posted units, and both intervals span zero. The registry record therefore does not show a clear difference in the primary measure in these comparisons.

This does not mean that the treatments are equivalent, that no difference exists, or that safety has been established. The confidence intervals retain uncertainty, and the registry record does not provide a prespecified equivalence margin or a reported adjusted analysis. A nonsignificant result is not proof of no effect. Likewise, the primary endpoint alone cannot answer questions about longer-term outcomes, symptoms, or all aspects of safety.

The trial’s stated purpose included assessing benefits and safety, but each result must be interpreted according to its outcome and timeframe. The primary measure covers randomization to 72 hours. Secondary measures address other outcomes and timepoints; they should not be collapsed into a single general claim about benefit. The registry’s dyspnea substudy also concerns measurement sensitivity, but its numerical findings are not reported in the registry record.

The serious adverse-event counts are descriptive, and the registry does not report an inferential comparison or causal attribution for those events. Differences in counts should not be taken as proof that one group had greater or lesser treatment-related risk. The death counts are not reported in the registry record.

In sum, the registry record supports a cautious description of the posted means, estimates, uncertainty, and event counts. It does not establish equivalence, rule out clinically important effects, or answer questions beyond the registered outcomes and reported analyses.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate should not be interpreted in isolation. The primary arm means are similar, and the unadjusted differences are accompanied by intervals that span zero. The point estimates summarize direction and magnitude, while the intervals show that the comparisons remain uncertain. Reporting both is essential for distinguishing a small observed estimate from a precise estimate.

It also highlights the difference between a safety endpoint and a complete safety conclusion. Cystatin C change is identified as the primary safety endpoint, but the registry’s serious adverse-event counts are separate descriptive data. Neither the laboratory endpoint nor event counts alone establish an overall safety profile. Clear interpretation depends on knowing how each outcome was defined, assessed, and analyzed.

The three-arm structure creates separate treatment-versus-placebo contrasts. This supports a clear reading of each active treatment against the shared comparator, but it does not establish a direct difference between the active treatments. Multiple endpoints and contrasts also make multiplicity relevant. Because the registry record does not report an analysis hierarchy or adjustment strategy, nominal results should be interpreted cautiously.

Finally, the record distinguishes observed results from planning illustrations. The sample-size calculations use observed effects and stated hypothetical assumptions; they cannot establish the trial’s original design rationale or its observed power. Keeping those concepts separate prevents retrospective calculations from being mistaken for evidence about the trial’s planning or the certainty of its results.

18. 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 registry record does not report the detailed eligibility criteria, the primary analysis population, or the analysis model. Without those details, it is not possible to determine precisely who contributed to each endpoint or whether the recalculated contrasts correspond to the trial’s intended primary analysis.

Although the study is listed as quadruple-masked and randomized, the record does not describe the randomization procedure, allocation concealment, or which roles were masked. The arm descriptions refer to treatment during the first 72 hours, but the registry record does not provide further information about adherence, treatment discontinuation, or concomitant care.

The primary endpoint is an early change in cystatin C. The registry record does not state a clinically important difference for this measure, and the listed time window does not address longer-term outcomes. The dyspnea substudy is described, but its numerical results are not reported in the registry record. Numerical results are also not available for every secondary outcome named in the record.

Counts differ across outcome summaries, and the reason is not reported in the registry record. Missing-data handling, sensitivity analyses, and rules for inclusion or exclusion are also not reported. The record does not provide a detailed multiplicity strategy or confirmatory testing hierarchy. These gaps limit assessment of robustness and make unadjusted secondary comparisons particularly difficult to interpret.

These limitations concern what the registry record documents. They do not establish that particular procedures were absent from the full trial conduct or reporting; they identify matters that cannot be assessed from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network (ROSE) Study — NCT01132846.
• Registry record last updated 2014-08-21; status last verified 2014-08.
• Results first posted 2014-08-21.
• 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.

22. Record Summary

ROSE is a completed, randomized, quadruple-masked, parallel-group phase 2 study sponsored by Duke University. The registry lists enrollment of 360 and describes low-dose dopamine, low-dose nesiritide, and placebo for people with acute heart failure and kidney dysfunction.

The primary safety endpoint was mean change in serum cystatin C from randomization to 72 hours. Posted mean changes were 0.12 for dopamine, 0.11 for placebo, and 0.07 for nesiritide. The unadjusted treatment-versus-placebo comparisons are imprecise, with both confidence intervals spanning zero. The registry record does not report a sponsor analysis, detailed analysis plan, multiplicity strategy, missing-data methods, or analysis population.

Secondary outcomes and serious adverse-event counts provide additional descriptive context, but they do not resolve the uncertainty in the primary comparisons or establish an overall treatment effect. The record’s sample-size illustrations are retrospective planning calculations, not observed power or the trial’s original design justification.