Oral Sodium to Preserve Renal EfficiencY in Acute Heart Failure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral Sodium to Preserve Renal EfficiencY in Acute Heart Failure (NCT04334668), a randomized na study. The primary outcome is Change in Weight.

2. Clinical Question

3. Trial Design

The registry describes OSPREY-AHF as a prospective, randomized, double-blind, placebo-controlled, single-center study. The design is parallel, with Oral Sodium Chloride and Placebo as the two arms. The listed allocation is randomized, but the method used to generate or conceal the allocation sequence is not reported in the registry record. The record identifies the study as phase NA.

The listed enrollment is 67. The posted outcome summaries include 34 participants in the Oral Sodium Chloride arm and 31 in the Placebo arm. These are the group sizes attached to the posted primary outcome; the record does not explain the difference between these outcome counts and the listed enrollment. It also does not report participant flow, withdrawals, or the number included in each analysis population.

The intervention description specifies oral sodium chloride, 2 grams three times daily with meals for approximately 4 days. The placebo was given orally three times daily with meals for approximately 4 days. Both were studied in the setting of intravenous diuretic treatment, as described in the registry summary. Further details of the background diuretic regimen, treatment adherence, and the masking procedures are not reported in the registry record.

The primary outcome is change in weight from baseline to 96 hours. The registry lists two outcome measures, but no secondary outcome results are posted in the record. The study status is active, not recruiting. The listed start date is 2020-05-20 and the primary completion date is 2022-06-01. The sponsor is The Cleveland Clinic.

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 Weight, measured over Baseline to 96 hours.

The primary endpoint is mean change in weight, measured in kilograms from baseline to 96 hours. The registry reports the mean and standard deviation for each arm. A negative change represents a decrease in weight over the measurement period, while the between-arm mean difference compares the average changes in the two groups.

Weight change is used in this study as an indicator of effective diuresis, as described in the registry hypothesis. In general, a continuous endpoint preserves information about the amount of change rather than reducing the result to categories such as whether a participant did or did not cross a threshold. Comparing group means can therefore describe the average change in each randomized arm and the estimated difference between those averages.

Weight change does not, on its own, describe every aspect of diuresis or renal function. Although the registry hypothesis mentions renal function, the posted primary outcome described in the record is weight change. A renal-function outcome result is not reported in the registry record. The endpoint also does not indicate how individual participants changed: a group mean and standard deviation summarize the group, not each participant’s experience.

The chosen measurement window is baseline to 96 hours. The registry does not report additional details about how or when weights were measured within that window, how missing measurements were handled, or whether the endpoint was analyzed in a defined analysis population.

7. Results Posted in the Registry

• Oral Sodium Chloride: mean -3.90 versus -4.60 on control; difference 0.70 (95% CI -1.37 to 2.77), standardized effect d = 0.16; z-test p = 0.507.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted endpoint is continuous: change in weight measured in kilograms. The registry identifies the arm-level summary as a mean with a standard deviation. A mean describes the arithmetic center of the observations in a group. A standard deviation describes how spread out individual observations are around that group mean. In general, a larger standard deviation indicates more variability among the measured values, but it does not show the shape of the distribution or reveal the values for individual participants.

What does the mean difference represent?

The comparison is expressed as the Oral Sodium Chloride mean minus the Placebo mean. The posted means are -3.9 and -4.6 kilograms, respectively, and the recalculated, unadjusted mean difference is 0.7 kilograms. The sign depends on the order of subtraction: a positive estimate means the first arm’s mean change is numerically greater than the second arm’s mean change. The estimate is a comparison of group averages, not a statement that every participant changed by that amount.

In general, a difference in means is a natural summary when an outcome is continuous and the question concerns average change between two groups. The calculation is unadjusted: it uses the posted group summaries and does not account for other participant characteristics or covariates. The registry record does not report a more detailed statistical analysis plan, adjusted model, or sponsor-posted analysis for the primary comparison.

How should the p-value be understood?

The unadjusted p-value is 0.507. In general, a p-value describes how compatible the observed data are with a specified null model, under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. A p-value also does not tell readers whether an analysis was prespecified or whether other outcomes or analyses were considered. Such details are not reported in the registry record.

The p-value should be interpreted with the estimated difference and its interval, not in isolation. The posted interval extends from -1.368 to 2.768 and includes zero. This is consistent with uncertainty about the direction and magnitude of the difference. The record does not report the confidence level used for the interval, so the interval should be described by its posted limits rather than assigned an unreported confidence percentage.

Why does variability matter?

In general, variability affects how precisely a group mean and a between-group comparison can be estimated. When measurements vary substantially among participants, a given group size may yield less precise estimates than it would for more tightly clustered measurements. Here, the arm-level standard deviations are 4.3 and 4.2 kilograms, while the posted group sizes are 34 and 31. These summaries provide context for the uncertainty but do not reveal whether the distribution is symmetric, skewed, or affected by outlying values.

Normal-based methods are among the possible approaches for comparing means. The sample-size planning illustration explicitly uses a normal approximation, but the registry record does not identify the method used for the trial’s own primary analysis. No assumptions about that original analysis should be inferred from the planning illustration. Details such as transformations, robust methods, covariate adjustment, and handling of missing outcome measurements are not reported in the registry record.

What does randomization add?

In general, random allocation is intended to make treatment groups comparable on average with respect to measured and unmeasured characteristics, subject to the way the trial is conducted. This rationale supports interpreting an arm comparison as a randomized comparison rather than a simple observational association. However, the record does not give the sequence-generation method, allocation concealment details, or procedures for maintaining masking. The study is described as randomized and double-blind, but the operational details are not reported in the registry record.

Because the design is parallel, participants are assigned to one of the two arms rather than crossing between both interventions, according to the design description. The registry does not provide further detail about adherence, crossovers, or whether analyses retained participants in their assigned arms. Those details can affect interpretation of a randomized comparison and cannot be reconstructed from the posted group summaries.

The comparison values are labeled recalculated because they are simple, unadjusted calculations based on the posted summary statistics. They should be distinguished from an analysis reported by the trial investigators. The record does not post a sponsor analysis result, and no details of a formal statistical analysis plan are reported in the registry record. The recalculated comparison therefore describes what follows from the posted summaries, not a substitute for unreported analyses.

10. Confidence Intervals and Precision

The recalculated unadjusted mean difference in weight change is 0.7 kilograms, with an interval from -1.368 to 2.768. The interval expresses uncertainty around the estimated difference; it is not a range containing every participant’s change. The posted limits include zero and extend to values on both sides of zero, so the summaries do not determine a precise direction or magnitude for the between-arm difference.

In general, an interval estimate gives a range of values that are reasonably compatible with the data under the method used to construct it. Its width reflects uncertainty, which can be influenced by group size, outcome variability, and analysis assumptions. A wider interval generally indicates less precision than a narrower interval. The confidence level and construction method for this posted interval are not reported in the registry record, so those details cannot be assessed from the record.

The point estimate, 0.7 kilograms, should not be treated as an exact effect. It is one estimate based on the posted group means. The interval indicates that appreciable uncertainty remains around it. The group standard deviations are 4.3 and 4.2, and the outcome summaries include 34 and 31 participants in the respective arms; these figures describe the data contributing to the posted summaries but do not establish whether all randomized participants had outcome measurements.

Precision is distinct from importance. An interval can help show what effect sizes the data remain compatible with, but the registry does not give a threshold for a clinically meaningful difference in weight change. Without such a threshold, and without the interval’s stated confidence level or the trial’s original analysis details, the precision and practical importance of the estimate cannot be fully characterized.

11. 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 planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total trial enrollment figures. For time-to-event planning, the general convention is to report total events, but this endpoint is continuous, so these entries refer to participants per arm.

The illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as its starting point and then considers planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The listed figures for these assumptions are 580 and 776 participants per arm for the observed effect; 1,031 and 1,379 participants per arm for 75% of the observed effect; and 2,318 and 3,103 participants per arm for 50% of the observed effect. Within each pair, the first figure is for 80% power and the second is for 90% power.

In plain terms, the 80% power column represents the planned number per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect is present. The 90% power column represents the corresponding planning target for a 90% chance. These are design concepts, not guarantees about a future study’s result. Smaller effects require more participants under the same planning assumptions, which is why the figures rise when planning for a smaller fraction of the observed effect.

This is a planning illustration based on the observed effect, not the trial’s original design calculation, and it is not observed power. The trial’s original sample-size justification and design assumptions are not reported in the registry record.

12. 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 = 0.700; pooled standard deviation σ = 4.253.
2. n = 2 × (1.96 + 0.842)² × 4.253² / 0.700² = 579.4, rounded up to 580 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 <- 0.7                      # observed difference in means
sigma <- 4.25267422867519                     # 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(4334668)
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 = 580 (80% power), 776 (90% power)
 75% of observed effect: n per arm = 1,031 (80% power), 1,379 (90% power)
 50% of observed effect: n per arm = 2,318 (80% power), 3,103 (90% power)
power.t.test: 580.3 
Simulated power at n = 580 per arm: 0.803 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures, but no secondary outcome results are posted. The primary endpoint described in the posted results is change in weight from baseline to 96 hours. The record does not give a complete list of outcome results or indicate whether any outcomes were added, removed, or changed during the study.

Multiplicity arises in general when several outcomes, time points, subgroups, or statistical comparisons are tested. If many tests are considered, the chance of at least one apparently notable result can increase unless the analysis accounts for the number and structure of the tests. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a prespecified primary analysis plan. It is therefore not possible to determine from the posted information how multiplicity was handled.

Missing-data handling is also not reported in the registry record. The outcome summaries include 34 participants in the Oral Sodium Chloride arm and 31 in the Placebo arm, while listed enrollment is 67. The record does not explain the participant flow or whether these outcome counts reflect all randomized participants, available measurements, or a particular analysis population. There is no posted description of imputation, exclusion rules, sensitivity analyses, or how missing weights were addressed.

The analysis population is not specified. In general, an intention-to-treat analysis retains participants in their randomized groups, while other analysis populations can apply additional eligibility or adherence criteria. The registry does not report which approach was used, or whether more than one population was analyzed. Nor does it describe treatment adherence or protocol deviations relevant to analysis inclusion.

These omissions limit assessment of whether the posted comparison follows a prespecified plan and how robust it is to missing observations or multiple analyses. They do not establish that any particular method was or was not used; those methods are simply not reported in the registry record.

14. 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: worsening renal function (3.2%), hypokalemia (3.2%), icu transfer (3.2%), readmitted (3.2%), vf arrest (3.2%).

The posted safety figures list serious adverse events affecting 7 participants in the Oral Sodium Chloride arm and 7 in the Placebo arm. Other adverse events affected 4 participants in each arm. The record lists 34 and 31 participants at risk for these categories, respectively. These are the posted counts; they should not be read as a comparison adjusted for follow-up time or as a complete description of event timing.

The listed deaths are 3 in the Oral Sodium Chloride arm and 3 in the Placebo arm. The registry record does not give further details in the figures about causes, timing, or attribution. The most frequent serious terms listed include Worsening Renal Function, Hypokalemia, ICU transfer, Readmitted, VF arrest, and Readmission, each reported as 3.2%. The overlapping wording of Readmitted and Readmission is retained as listed in the record.

In general, adverse-event counts describe events recorded under the study’s reporting definitions; they do not by themselves establish that an intervention caused an event. The registry does not report detailed event narratives or comparative safety analyses in the record summarized by these figures. The counts also do not show the severity, duration, or relationship to treatment for each individual event unless those details are separately reported.

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

The posted primary outcome describes average weight change over the specified period in the two randomized groups. The Oral Sodium Chloride group mean was -3.9 kilograms, and the Placebo group mean was -4.6 kilograms. The recalculated unadjusted difference was 0.7 kilograms, with an interval from -1.368 to 2.768 and an unadjusted p-value of 0.507. These statistics show the observed group summaries and the uncertainty around their comparison; they do not establish a definitive difference between the groups.

The result does not, by itself, establish whether oral sodium chloride improves diuresis or renal function. The registry’s stated hypothesis includes renal function, but no renal-function result is reported in the registry record. The posted weight endpoint is an indicator used in the study’s stated hypothesis, not a complete measure of every outcome relevant to acute decompensated heart failure.

The result also does not show how much any individual participant’s weight changed, or whether every participant had a measurement at 96 hours. The record does not report missing-data methods, participant flow, or the analysis population. It therefore cannot establish from the posted summaries alone how broadly the arm-level comparison represents all enrolled participants.

General interpretation of a randomized study depends on both the design and the conduct of the trial. The registry describes randomization and double blinding, but does not report details of the allocation process, masking procedures, treatment adherence, or the primary analysis plan. Those details matter for evaluating how the comparison was implemented, but should not be guessed from the design labels.

The adverse-event counts are descriptive and do not establish causation. The sample-size figures are planning illustrations based on the observed effect, not evidence about the trial’s ability to detect an effect after the results were observed. The registry record’s status and dates likewise do not change the interpretation of the posted outcome statistics. Overall, the evidence described in the record is limited to the posted group summaries and should be interpreted with the uncertainty and reporting gaps in view.

16. Why This Trial Matters Statistically

This trial raises a statistical question about how to compare a continuous outcome between randomized arms. Weight change is summarized by a mean and standard deviation, and the primary comparison is a difference between group means. This approach gives a concise estimate of the average contrast while preserving a measure of variation among participants.

The estimate needs to be read together with its interval. The recalculated mean difference is 0.7 kilograms, but the interval from -1.368 to 2.768 spans values on both sides of zero. The p-value of 0.507 offers another summary of the comparison under a statistical model, but it does not replace the estimate or its uncertainty. Emphasizing the point estimate alone would leave out the substantial uncertainty reflected in the interval.

The record also illustrates the difference between trial results and planning calculations. The sample-size illustration uses the observed effect and explicitly states its planning assumptions. It can show how the required group size changes when planning for smaller effects, but it does not reveal the assumptions used to design the actual trial. Nor is it observed power. The original sample-size rationale is not reported in the registry record.

Finally, statistical interpretation depends on reporting beyond a single outcome summary. The registry does not report the original analysis plan, analysis population, missing-data procedures, or multiplicity approach. It does not post secondary outcome results, including a renal-function result despite the stated hypothesis. Those gaps do not negate the posted weight summaries, but they constrain how completely readers can evaluate the analysis and its scope.

17. 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 posted record leaves important trial and analysis details unreported. It does not describe eligibility criteria in detail, the method of random sequence generation, allocation concealment, or how double blinding was maintained. It also does not report the intravenous diuretic regimen, treatment adherence, or protocol deviations. These details would help readers assess implementation and the context of the comparison.

The record lists enrollment of 67 and outcome counts of 34 and 31, but does not provide participant flow or explain whether the primary outcome summaries include all randomized participants. The analysis population and the handling of missing measurements are not reported. The absence of a posted secondary outcome result also means the stated renal-function hypothesis cannot be evaluated from the outcomes described in the record.

The primary comparison is an unadjusted recalculation from group summary statistics. The registry record does not report the trial’s statistical analysis plan, any covariate adjustment, sensitivity analyses, or the method used to construct the posted interval. Its confidence level is also not reported. No clinically meaningful threshold for weight change is given, limiting interpretation of the estimate’s practical importance.

The safety information is limited to the posted counts and serious-event terms. Further event-level details, timing, attribution, and the reporting definitions are not reported in the registry record. The single-center design is described in the study summary, which also means the record itself does not establish how broadly results apply beyond this study setting.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Oral Sodium to Preserve Renal EfficiencY in Acute Heart Failure — NCT04334668.
• Registry record last updated 2026-07-13; status last verified 2026-06.
• Results first posted 2024-03-12.
• 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.

21. Record Summary

OSPREY-AHF is described as a prospective, randomized, double-blind, placebo-controlled, single-center, parallel study sponsored by The Cleveland Clinic. The listed enrollment is 67, and the study status is active, not recruiting. The registry lists phase NA.

The intervention was oral sodium chloride, 2 grams three times daily with meals for approximately 4 days; the comparator was an oral placebo on the same schedule. The primary outcome was mean change in weight in kilograms from baseline to 96 hours. The posted means were -3.9 in the Oral Sodium Chloride arm and -4.6 in the Placebo arm. The recalculated unadjusted mean difference was 0.7, with an interval from -1.368 to 2.768 and an unadjusted p-value of 0.507.

The record does not post secondary outcome results or the trial’s original statistical analysis and sample-size assumptions. The sample-size figures are planning illustrations based on the observed effect, not the original design justification.