Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction (HFpEF) (INABLE-Training): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction (HFpEF) (INABLE-Training) (NCT02713126), a randomized phase 2 study. The primary outcome is Change in Peak Rate of Oxygen (VO2).

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, parallel phase 2 study. The registry lists an enrollment of 92 and a completed status. It records a start of 2016-09 and a primary completion date of 2022-04-12. The record identifies Barry Borlaug as sponsor and lists heart failure as the condition.

Participants were assigned to sodium nitrite or placebo while undergoing cardiac exercise training. Each arm description specifies three-times-daily study drug for 12 weeks and use of an accelerometer. The study summary adds that one dose was taken 30 minutes before exercise sessions. The registry describes each study drug as inhaled or oral, but does not clarify how routes were allocated or used in practice.

The primary outcome was change in peak rate of oxygen consumption, measured at baseline and 12 weeks. The posted arm summaries include 34 participants for placebo and 31 for sodium nitrite for this outcome. Those outcome-specific counts should be read as the denominators for the reported endpoint, not as a replacement for the enrollment figure. Denominators differ across the posted outcomes.

Four secondary outcomes are listed: daily activity levels, cardiac hemodynamics, Kansas City Cardiomyopathy Questionnaire overall summary score, and six-minute walk test. The record also lists five outcome measures and five analyses, while four secondary outcomes are posted with results. Additional details about the original sample-size justification, allocation procedures, and the 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.

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 Peak Rate of Oxygen (VO2), measured over Baseline, 12 weeks.

The primary endpoint is change in peak rate of oxygen consumption, or peak VO2, from baseline to 12 weeks. It is expressed in ml/min/kg. The registry describes it as the peak rate of oxygen consumption achieved during exercise testing, with oxygen consumption scaled to body mass. In general, peak oxygen consumption is used as a measure of exercise capacity because it quantifies oxygen use at the point of greatest exertion recorded during the test.

The endpoint is relevant to this study question because both groups participated in exercise training, and the trial asks whether sodium nitrite changes the response to that training compared with placebo. The comparison is between the mean changes in the two randomized groups, rather than a comparison of their 12-week values alone. A between-group difference in change expresses how the recorded average change differed between arms over the specified period.

The measure is continuous, so results are reported as means with standard deviations and as a mean difference. A mean gives the average change in a group; the standard deviation describes the spread of individual changes around that mean. Neither measure by itself describes every participant’s response. The registry does not report further details about exercise-testing procedures, endpoint adjudication, or handling of measurements that were unavailable at follow-up.

7. Results Posted in the Registry

• Sodium Nitrite: mean 0.70 versus 0.85 on control; difference -0.15 (95% CI -1.03 to 0.73), standardized effect d = -0.08; z-test p = 0.739.

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 Daily Activity Levels

• 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:
  • Sodium Nitrite: mean 23.00 versus -4.00 on control; difference 27.00 (95% CI -8.01 to 62.01), standardized effect d = 0.45; z-test p = 0.131.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sodium Nitrite and the control. The interval gives the range of effects that remain compatible with the data.

Change in Cardiac Hemodynamics

• 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:
  • Sodium Nitrite: mean -0.20 versus 1.10 on control; difference -1.30 (95% CI -3.97 to 1.37), standardized effect d = -0.34; z-test p = 0.339.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sodium Nitrite and the control. The interval gives the range of effects that remain compatible with the data.

Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score

• 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:
  • Sodium Nitrite: mean 4.90 versus 6.10 on control; difference -1.20 (95% CI -7.29 to 4.89), standardized effect d = -0.09; z-test p = 0.699.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sodium Nitrite and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address several dimensions beyond exercise capacity: daily activity, cardiac hemodynamics, the KCCQ overall summary score, and the six-minute walk test. The posted means and recalculated contrasts do not show a consistent pattern of clearly separated group results across these different measures. The associated confidence intervals include zero, leaving uncertainty about both direction and magnitude.

This overall pattern is compatible with the primary result in the limited sense that the secondary comparisons also do not establish a clear between-group difference in the posted summaries. It does not independently confirm the primary result, and the outcomes are not substitutes for peak VO2. Each measures a distinct construct, and secondary findings cannot by themselves resolve the uncertainty in the primary comparison.

The registry lists four secondary outcomes with posted results. Not every secondary outcome has the same outcome denominator, and the record does not explain the differences. The numerical secondary results should therefore be interpreted with attention to their own denominators and uncertainty, rather than as if they all arose from identical data coverage.

Unadjusted secondary p-values carry less weight when several outcomes are examined. In general, testing multiple outcomes increases the chance that at least one result may appear notable under random variation, even when no corresponding underlying effect exists. This is why a prespecified hierarchy or multiplicity strategy can matter. The registry record does not report whether secondary testing was adjusted, prioritized, or intended to support confirmatory conclusions. The secondary outcomes are best treated as additional descriptive evidence, not as a collection of independent definitive tests.

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

• Change in Daily Activity Levels
• Change in Cardiac Hemodynamics
• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
• Change in Six Minute Walk Test

9. Statistical Interpretation

10. Statistical Methods Explained

The primary analysis compares a continuous outcome between two randomized groups. The endpoint is each participant’s change in peak VO2 between baseline and 12 weeks. The registry posts a mean and standard deviation for each arm, a recalculated unadjusted mean difference, a confidence interval, and a p-value. It also reports its own two-sided t-test result.

What does the mean difference represent?

The contrast is sodium nitrite minus placebo. A negative estimate means that the posted mean change was lower in the sodium nitrite group than in the placebo group; a positive estimate would mean it was higher. The estimate of -0.15 ml/min/kg is the observed difference between the posted group means, not a statement that every participant in one arm changed by less than every participant in the other. Group distributions can overlap even when their means differ.

In general, a mean difference offers a direct expression of the contrast on the endpoint’s original scale. Its interpretation depends on understanding how the endpoint was defined and what direction of change represents. The registry defines the measure and timeframe, but does not report a threshold for what size of difference would be clinically important.

Why report a standard deviation?

The standard deviation describes variability among the recorded changes within an arm. It is not the uncertainty of the group mean itself. In general, the standard error of a mean depends both on the variability in the observations and on the number of observations; a more variable outcome or a smaller denominator tends to make the mean less precise. The posted standard deviations and outcome-specific denominators are therefore important context for the mean comparison.

The recalculated contrasts are unadjusted comparisons based on the posted summary statistics. They do not account for participant-level covariates or other adjustments. The registry record does not report adjusted estimates or enough detail to determine whether the sponsor’s analysis included additional features beyond the stated two-sided t-test. The recalculated results should not be mistaken for a reanalysis of individual participant records.

How should a p-value be read?

In general, a p-value describes how unusual data at least as incompatible with a null model would be if that model and the test assumptions held. It is not the probability that the null hypothesis is true, nor is it the probability that the observed result occurred “by chance” in a broad, assumption-free sense. A p-value does not measure the size or clinical importance of an effect. The recalculated primary p-value is 0.739, while the registry reports 0.770 for its two-sided t-test. Neither value proves no effect, equivalence, or a particular benefit.

The sample-size planning assumptions listed for the illustrations use a two-sided significance level of 0.05. That planning assumption should not be confused with a report of the trial’s original analysis plan. The original statistical plan and its decision rules are not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval shows a range of effect estimates compatible with the observed data under the interval method’s assumptions. It communicates precision and direction in a way a p-value alone cannot. For the primary comparison, the recalculated interval spans zero. Thus it includes the possibility of no mean difference as well as values on either side of zero. Its breadth also indicates that the available summary data do not pin down the effect precisely.

A confidence interval is not a guarantee that the true effect lies within its endpoints, nor does it assign probability to each possible value under the usual frequentist interpretation. The interval level is not identified in the posted comparison details, so no confidence percentage should be inferred from the record alone.

Why can reported and recalculated results differ?

The sponsor’s reported primary p-value and the unadjusted recalculation are not identical. A recalculation based on summary means, standard deviations, and denominators cannot reproduce every possible analysis choice that may have been used in an analysis of participant-level data. The registry does not explain the difference, and it does not report sufficient detail to attribute it to a particular method or data-handling decision. The reported analysis and the recalculation should therefore be kept distinct rather than treated as interchangeable.

For secondary outcomes, the same general principles apply: group means and spreads describe the data, mean differences express the contrasts, and intervals and p-values convey uncertainty under their respective methods. Because several outcomes are reported, interpreting each p-value as if it were the only test would overlook the broader set of comparisons. The record does not report a multiplicity adjustment or a detailed analysis plan.

11. Confidence Intervals and Precision

The primary mean-difference estimate is -0.15 ml/min/kg, and its recalculated confidence interval crosses zero. That interval does not isolate a direction of effect: values consistent with a lower mean change in the sodium nitrite group and values consistent with a higher mean change remain within the interval. The reported p-value and the interval address related questions, but the interval makes the range of plausible contrasts more visible.

Precision is limited by the amount and variability of the outcome data. For the primary endpoint, the standard deviations are 2.1 and 1.51 ml/min/kg, while the reported outcome denominators are 34 and 31. The estimated contrast is small relative to the within-group spread. This combination is consistent with an interval that does not tightly identify the between-group difference. It does not show that the true effect is exactly zero.

The secondary estimates likewise have intervals spanning zero. For example, the recalculated mean difference for daily activity levels is 27.0 accelerometry units, with an interval from -8.009 to 62.01. That range includes both negative and positive contrasts. The cardiac-hemodynamics and KCCQ intervals also span zero. Such intervals indicate that the summary data do not precisely distinguish a zero contrast from effects in either direction under the calculation used.

In general, confidence intervals describe statistical uncertainty, not all sources of uncertainty. They do not resolve concerns about missing outcome data, analysis choices, measurement quality, or the relevance of the outcome to patients. The registry record does not report the interval confidence level, missing-data procedures, or a clinically important-difference threshold for peak VO2. Those omissions limit how fully the numerical precision can be interpreted.

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 planning figures are for participants per arm, not total events. These are continuous-outcome illustrations, so the relevant unit is participants per arm. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. These planning calculations are not the original trial’s documented design assumptions; those assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the selected effect under the listed assumptions, if that effect and those assumptions were correct. The 90% power column uses a higher target chance of detection and therefore calls for more participants per arm for the same assumed effect. For the primary outcome, planning for 100% of the observed effect gives 2,370 participants per arm for 80% power and 3,172 for 90% power. Planning for 75% of the observed effect gives 4,212 and 5,639 participants per arm, respectively; planning for 50% gives 9,477 and 12,687.

The curve expresses the same general relationship visually: smaller effects are harder to distinguish from random variation, so they require more participants to reach the same target power. The illustrations are derived from the observed effect, which is itself uncertain and may not represent the effect in a future study. They are not observed power and do not show the probability that the completed trial’s result is correct. The registry’s own sample-size justification and original power target are not reported in the registry record.

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 = -0.150; pooled standard deviation σ = 1.843.
2. n = 2 × (1.96 + 0.842)² × 1.843² / -0.150² = 2,369.1, rounded up to 2,370 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 <- -0.15                      # observed difference in means
sigma <- 1.84275931818616                     # 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(2713126)
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 = 2,370 (80% power), 3,172 (90% power)
 75% of observed effect: n per arm = 4,212 (80% power), 5,639 (90% power)
 50% of observed effect: n per arm = 9,477 (80% power), 12,687 (90% power)
power.t.test: 2370.1 
Simulated power at n = 2,370 per arm: 0.795 (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. Analyses Reported by the Sponsor

The registry reports a two-sided t-test for the primary comparison, with p = 0.770. A separate unadjusted recalculation from the posted summary statistics gives p = 0.739 and a mean difference of -0.15 ml/min/kg. These figures are close in broad interpretation but are not identical. The registry does not explain the difference, so it cannot be attributed to a particular choice of analysis, rounding, or data handling on the basis of the record.

The sponsor’s own analysis is the result reported by the registry; the recalculation is a transparent, summary-statistic-based comparison rather than an independent reconstruction of participant-level data. It should not be substituted for the sponsor’s analysis or treated as an explanation for it. The record marks no discrepancy between the posted and recalculated results, but that does not mean the two p-values are numerically identical.

For secondary outcomes, the registry-reported two-sided p-values also differ from their unadjusted recalculations. Those pairs should likewise be read as results from distinct reported and recalculated analyses. The registry does not supply further details that would permit a full reconciliation.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and five analyses, with the primary outcome identified as change in peak VO2 and four secondary outcomes posted. Evaluating several outcomes creates a multiplicity issue: in general, the more statistical comparisons made, the greater the chance of obtaining at least one apparently unusual result even when the underlying effects are absent. Interpretation can depend on whether outcomes were prespecified, whether a hierarchy was used, and whether p-values were adjusted for multiple testing.

Those details are not reported in the registry record. It does not state whether the secondary analyses were exploratory or confirmatory, whether any adjustment was applied, or whether an outcome hierarchy governed interpretation. Consequently, the reported secondary p-values should not be read as though each arose from a single isolated test. The record also does not describe interim analyses or stopping rules.

Outcome denominators vary across the primary and secondary results. The posted primary endpoint uses 34 participants in the placebo arm and 31 in the sodium nitrite arm; other outcomes have different denominators. The record does not report why measurements are absent from some endpoint summaries, how missing values were handled, or whether an imputation or sensitivity analysis was used. It also does not identify the analysis population used for each result, such as whether all randomized participants were included in the primary analysis.

These omissions matter because missingness can affect both precision and interpretation, especially if the availability of measurements is related to participants’ outcomes. The posted means and comparisons remain informative descriptions of the registry results, but the record does not allow a complete assessment of how missing data or multiple testing were addressed. No assumptions about those procedures can be inferred from the reported numbers alone.

16. 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: severe chest/neck/jaw pain (5.4%), pneumonia (5.4%), serious fall resulting in injury (2.8%), gi bleed (2.8%), dizziness/lightheadedness (2.8%).

The registry reports serious adverse events using an at-risk denominator and an affected count for each arm. For placebo, 3 were affected among 36 at risk; for sodium nitrite, 7 were affected among 37 at risk. Deaths are reported as 0 in each arm. These figures describe the registry’s serious-event reporting; they do not establish that any difference between arms was caused by the assigned study drug.

The record also gives figures for other adverse events: 36 affected among 36 at risk in the placebo group and 37 affected among 37 at risk in the sodium nitrite group. The registry lists serious-event terms with percentages, including Severe Chest/Neck/Jaw Pain and Pneumonia at 5.4% each, as well as several terms at 2.8%. The list does not identify the treatment arm for each term in the posted information, so those percentages should not be assigned to a particular arm.

In general, adverse-event counts require context about event definitions, ascertainment, severity, timing, and attribution. The registry record does not provide enough detail in these results to determine causality or make a comparative safety conclusion. The counts are descriptive and should be read alongside the limits of the reported follow-up and event information.

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

The posted primary result is a small negative mean difference in change in peak VO2 for sodium nitrite relative to placebo, with substantial uncertainty. The recalculated confidence interval crosses zero, and the registry-reported two-sided p-value is 0.770. Together, these results do not establish a clear difference between groups in mean change over the stated period. They also do not prove that the treatments have identical effects or that no effect is possible.

The comparison answers a specific question: sodium nitrite versus placebo when both groups received cardiac exercise training. It does not compare exercise training with no exercise training. The study summary describes a 12-week training and medication period, and the primary endpoint is assessed from baseline to 12 weeks. The result should not be extended to other durations, populations, routes of administration, or treatment settings that are not described in the registry record.

Statistical evidence and clinical importance are separate. The registry does not report a threshold for a clinically important change in peak VO2, so the posted difference cannot be classified against such a threshold using the record alone. The confidence interval addresses precision under its statistical assumptions; it does not capture every uncertainty related to missing data, measurement, or study conduct.

The secondary results do not remove the uncertainty in the primary result. They concern different outcomes, have varying denominators, and are accompanied by no reported multiplicity strategy. Safety counts are also descriptive and do not establish causation. Overall, the registry results support a cautious account of what was observed in the reported comparisons, rather than a broad conclusion about treatment efficacy or safety.

18. Why This Trial Matters Statistically

This trial raises a useful statistical question about how to interpret an intervention added to a shared behavioral treatment. Because both randomized groups received cardiac exercise training, the primary contrast estimates the difference associated with assignment to sodium nitrite rather than placebo during training. It does not isolate the effect of training itself. Clear identification of that comparison prevents overstatement of what randomization can answer.

The trial also illustrates why point estimates, intervals, and p-values should be read together. The primary mean difference is -0.15 ml/min/kg, while the recalculated interval spans zero and the registry-reported p-value is 0.770. The point estimate alone might invite an overly simple directional reading; the interval shows that the available information leaves meaningful uncertainty about the contrast.

Planning illustrations make another statistical issue visible: sample-size requirements depend strongly on the effect chosen for detection. Smaller assumed effects require more participants per arm to attain the same target power. Because these illustrations use the observed effect, they are not a substitute for the original trial’s planning rationale, which is not reported in the registry record.

Finally, the varying outcome denominators and unreported multiplicity and missing-data procedures show why registry summaries are not the whole analysis record. They can communicate the principal numerical findings, while leaving important methodological questions unresolved. Reading estimates alongside those limitations is essential to a calibrated interpretation.

19. 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.

Several trial-specific limits constrain interpretation. The primary outcome denominators are 34 for placebo and 31 for sodium nitrite, while the registry enrollment is 92. The record does not explain the difference between enrollment and the outcome-specific counts, or describe the handling of unavailable measurements. Denominators also vary across the secondary outcomes, with no account of the reasons.

The registry reports a completed phase 2 trial and a 12-week training and study-drug period, but does not report the original sample-size justification or the trial’s planned power. The sample-size illustrations based on the observed effect are planning examples, not evidence that the trial was adequately or inadequately powered under its original design. The statistical analysis plan, analysis populations, and any interim analyses are not reported in the registry record.

The record does not explain the difference between the sponsor-reported and recalculated p-values, provide a multiplicity strategy, or describe missing-data sensitivity analyses. It also does not give a clinically important-difference threshold for the primary endpoint. These gaps limit evaluation of how robust the estimates are and how large a difference would matter clinically.

The medication route is described as inhaled or oral, without a route-specific account. The posted results do not establish whether outcomes differed by route or provide enough detail to assess that question. Finally, the results cover the stated baseline-to-12-week timeframe; longer-term outcomes are not reported in the information available in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction (HFpEF) (INABLE-Training) — NCT02713126.
• Registry record last updated 2023-04-26; status last verified 2023-04.
• Results first posted 2023-04-26.
• 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.

23. Record Summary

The registry describes a randomized, double-masked, parallel phase 2 trial of sodium nitrite versus placebo during cardiac exercise training for heart failure with preserved ejection fraction. Enrollment is listed as 92, and the trial status is completed. The primary outcome is change in peak VO2 from baseline to 12 weeks.

The posted primary comparison gives a recalculated mean difference of -0.15 ml/min/kg, with an interval spanning zero. The registry-reported two-sided p-value is 0.770. These results do not establish a clear between-group difference, while leaving uncertainty about the size and direction of the underlying effect.

Four secondary outcomes and adverse-event summaries are also reported. Their interpretation is limited by varying outcome denominators and by the absence of registry entries on missing-data handling, multiplicity, and the original statistical plan. The secondary and safety results are descriptive and should be read with those limitations in mind.