Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy (NCT01150461), a randomized phase 2 study. The primary outcome is Percentage Change From Baseline in Extent of Left Ventricular Fibrosis at 1 Year as Assessed by Magnetic Resonance Imaging..

2. Clinical Question

The registry describes the purpose as examining whether losartan affects heart muscle thickening and/or scarring in people with nonobstructive hypertrophic cardiomyopathy. The primary outcome addresses the scarring part of that question: it measures change in the extent of left ventricular fibrosis. The secondary outcome listed is percentage change from baseline in left ventricular mass at 1 year, assessed by magnetic resonance imaging. The record does not provide a result for that secondary outcome in the posted results.

This is a comparison of assigned treatment groups, not a report of each participant’s experience or a direct measure of symptoms. Although the brief study summary mentions feeling better as part of the study’s purpose, the primary outcome is an imaging measure of fibrosis. The registry record does not report a primary symptom or quality-of-life outcome. The reported statistical comparison therefore concerns the fibrosis outcome, and should not be read as a direct answer about how participants felt.

3. Trial Design

The study is listed as a phase 2 randomized trial with a parallel-group model and triple masking. It compared losartan 50 mg by mouth twice daily with placebo twice daily. The registry reports enrollment of 20 and lists Massachusetts General Hospital as the sponsor. The study status is completed. The recorded start is 2007-02, and primary completion is recorded as 2010-07.

Random allocation is intended to make treatment groups comparable on average, while masking is intended to limit the influence of treatment knowledge on participants, care, and assessment. Those are general features of trial design; the registry record does not specify who was masked or how allocation was generated or concealed. It also does not describe the procedures used to maintain masking. The parallel design means the registry presents separate groups assigned to losartan or placebo rather than describing a crossover comparison.

The primary outcome was percentage change from baseline in the extent of left ventricular fibrosis at 1 year, assessed by magnetic resonance imaging. The record also lists percentage change from baseline in left ventricular mass at 1 year as a secondary outcome. The primary analysis reported in the registry uses the Wilcoxon (Mann-Whitney) method. Other details of the statistical plan, including the analysis population, missing-data procedures, and any planned adjustments, are not reported in the registry record.

The enrollment figure describes the trial’s recorded enrollment, not necessarily the number included in every outcome analysis. For the fibrosis outcome, the posted group summaries list 11 participants in the losartan group and 9 in the placebo group. The record does not explain whether these numbers reflect all randomized participants, participants with available outcome measurements, or another analysis population. No further participant-flow details are reported.

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 Percentage Change From Baseline in Extent of Left Ventricular Fibrosis at 1 Year as Assessed by Magnetic Resonance Imaging., measured over Baseline and 1 year.

The primary endpoint is percentage change from baseline in the extent of left ventricular fibrosis at 1 year, assessed by magnetic resonance imaging. Fibrosis refers to scar tissue in the heart muscle; the registry’s study summary describes the broader research question as involving heart muscle scarring. The endpoint therefore uses an imaging measure to represent change in a structural feature of the left ventricle over the stated follow-up period.

Expressing change as a percentage relates the follow-up measurement to the participant’s baseline measurement. In general, a change measure can help describe whether the measured feature increased or decreased over time, while accounting for the starting value in the way specified by the study’s endpoint. The registry does not give the precise formula used to calculate percentage change, the imaging acquisition or reading procedures, or how measurements were reviewed. Those details are not reported in the registry record.

The registry identifies the outcome parameter as a mean and its dispersion as a standard deviation. The posted group means are -23.0 for losartan and 31.0 for placebo, with standard deviations of 45.0 and 26.0, respectively. The outcome is clinically relevant to the stated study question because it quantifies imaging-assessed fibrosis rather than symptoms or functional status. It should not be treated as interchangeable with left ventricular mass, which is listed separately as a secondary outcome, or with how participants felt. The registry does not report a result for the listed secondary outcome in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a Wilcoxon (Mann-Whitney) test for the comparison of losartan and placebo on the primary continuous outcome. This is a rank-based method: rather than comparing only the arithmetic means, it uses the ordering of observations across the groups. In general, such a test can be useful when a comparison is framed around the relative distributions or ordering of observations and when a mean-based model may not be a suitable description. Interpreting it as a test of a difference in medians requires additional assumptions about the shapes of the group distributions; those distributional details are not reported in the registry record.

The registry gives a p-value of 0.02 for the reported test. In general, a p-value measures how unusual data at least as discordant with a specified null model would be if that model and the test assumptions held. It does not indicate the probability that the null model is correct. It also does not measure the size of the group difference, the probability of benefit, or the importance of an outcome to participants. The registry does not state the precise null hypothesis or any additional test details beyond the method name and p-value.

The outcome is identified as a mean with standard deviation. A mean summarizes the arithmetic average, while a standard deviation describes the spread of observations around that average. Those summaries are informative about location and variability, but they do not show the shape of the outcome distribution or identify outliers. The rank-based test and the mean-and-standard-deviation summaries answer related but not identical descriptive questions. The reported p-value should therefore be understood as belonging to the named rank-based comparison, not as a test that can be reconstructed from the means and standard deviations alone.

A confidence interval generally gives a range of values compatible with data and a specified statistical procedure, while communicating uncertainty around an estimate. The registry record does not report a confidence interval for the between-group comparison. The low and high values listed alongside the individual group summaries are not identified in the record with enough detail to interpret them as a confidence interval for the treatment contrast. They should not be used as though they quantify the uncertainty of the Wilcoxon comparison.

Variability matters when interpreting a continuous outcome. In general, a large spread relative to the group’s central value can make a group mean less representative of individual observations, and can contribute to uncertainty in comparisons. The reported standard deviations are 45.0 for losartan and 26.0 for placebo, against means of -23.0 and 31.0. Those summaries show that observations varied within both groups, but the registry does not provide the underlying participant-level values or a distributional plot description from which to evaluate skewness, outliers, or other distributional features.

Over-dispersion is a general concern most often discussed for count outcomes: it occurs when observed variability exceeds what a chosen count model assumes, and can make standard errors too small if ignored. The primary outcome is continuous, so a count-model over-dispersion issue is not the central concern. For this endpoint, the relevant general questions include the shape of the measurements, the effect of extreme observations, and whether the chosen test’s assumptions are reasonable. The registry does not report diagnostics or details that would resolve those questions.

The record labels the trial randomized, triple-masked, and parallel-group. In general, random allocation supports a comparison between assigned groups, and masking can reduce the influence of treatment knowledge on participant reporting, care, and outcome assessment. However, the registry does not state the allocation procedure, the identities of the masked parties, or how masking was maintained. Those missing details limit assessment of how these design protections were implemented.

The registry also includes planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation, and a normal approximation, with planning based on a stated fraction of the observed effect. Such calculations are prospective illustrations under assumptions, not evidence of the trial’s actual design rationale and not observed power. The record does not report a sample-size justification, and no specific planning counts are included in the registry record described for this analysis. These illustrations should not be used to claim that the trial had a particular probability of detecting an effect.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("Losartan 50 mg PO BID", "Placebo")
n   <- c(11, 9)
m   <- c(-23, 31)
sp  <- c(45, 26)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Losartan 50 mg PO BID  11  -23.000  45.000  -53.231  7.231
CARM  Placebo  9  31.000  26.000  11.015  50.985

11. Analyses Reported by the Sponsor

The sponsor-reported analysis is a Wilcoxon (Mann-Whitney) comparison, with p = 0.02. This is the analysis to use when describing the registry’s reported inferential result. The group means and standard deviations provide descriptive summaries, but do not contain the participant-level ranks needed to reproduce a Wilcoxon test. The registry does not report a between-group estimate with a confidence interval for the primary comparison.

A separate unadjusted recalculation of the comparison is not estimable from the available posted summary statistics, as noted in the registry record. It therefore does not provide an alternative estimate or p-value to set against the sponsor’s result. The sponsor’s own analysis is the relevant reported analysis; no discrepancy is flagged in the registry record. The reported p-value should still be interpreted in light of the limited information about the analysis population, missing measurements, and statistical plan.

The posted summaries show a mean of -23.0 in the losartan group and 31.0 in the placebo group. These are group-level descriptive values, not an independently recalculated treatment contrast. They should not be presented as though they were an estimated difference with known precision. The reported Wilcoxon result and the descriptive means answer related but distinct statistical questions, and the available record does not supply enough detail to bridge them into a fully specified effect estimate.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary fibrosis outcome and a secondary outcome measuring percentage change from baseline in left ventricular mass at 1 year. It also states that there are 2 outcome measures and 2 analyses. The registry entries available for the reported results include the primary fibrosis comparison and do not provide a numerical result for the listed secondary outcome. The full set of outcome measures, analysis details, and any distinctions between planned and reported analyses are not described beyond these entries.

Multiplicity arises when several outcomes, time points, treatment comparisons, or statistical tests are examined. In general, conducting multiple tests can increase the chance of at least one apparently unusual result under a collection of null hypotheses. Methods such as prespecifying a primary outcome or adjusting inference can address aspects of that issue. The registry record does not report a multiplicity strategy, whether any adjustment was planned, or whether the p-value of 0.02 was adjusted. It is therefore not possible to determine how the reported result should be interpreted in relation to the full family of analyses.

The analysis population is not reported in the registry record. The outcome summaries list 11 participants in the losartan group and 9 in the placebo group, but the record does not state whether these represent all randomized participants, a modified intention-to-treat set, a per-protocol set, or participants with measurements available at 1 year. The registry also does not report participant flow or reasons for any absent endpoint data.

Missing-data methods are likewise not reported. In general, missing outcome measurements can affect a comparison if their occurrence or their likely values differ between groups. Without the number and pattern of missing measurements, the reasons for missingness, and the analytic approach, the direction or magnitude of any resulting influence cannot be assessed. The record does not describe imputation, sensitivity analyses, or other procedures for handling missing data. These omissions leave uncertainty about the population and data contributing to the reported p-value.

13. 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 1% reporting threshold.

The posted safety figures record 0 serious adverse events among 11 participants at risk in the losartan group and 0 among 9 participants at risk in the placebo group. The record also lists 0 other adverse events in each group. These figures describe the events reported in the registry; they do not establish that no events occurred outside the categories or reporting period represented by those entries.

Death counts are listed as null for both groups. A null entry is not the same as a reported count of zero, so deaths should be described as not reported in the registry record rather than as absent. The record does not provide serious adverse event terms, timing, severity details, or further context for the event counts. It also does not give a fuller description of safety monitoring or the period over which these figures were collected.

In general, safety event counts in a small trial are descriptive and may be imprecise. A zero count in the registry does not rule out possible harms, and the record does not support a broad safety conclusion. The figures should be read narrowly as the posted adverse-event entries for the listed groups, with the missing context and unreported death values kept in view.

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

The registry reports a mean percentage change in left ventricular fibrosis of -23.0 for the losartan group and 31.0 for the placebo group, alongside a Wilcoxon (Mann-Whitney) p-value of 0.02. These are the central findings available for the primary outcome. The means describe the observed group summaries, while the p-value describes the result of the reported rank-based test under its statistical framework. Neither item alone gives a complete account of the magnitude and precision of the between-group effect.

The result does not establish how participants felt, whether their symptoms changed, or whether their daily functioning changed. The primary endpoint is an imaging measure of fibrosis. Although the registry’s brief summary links the study’s purpose to heart muscle thickening and scarring and mentions feeling better, the posted primary result does not measure symptom experience directly. The secondary outcome concerning left ventricular mass is listed, but a result for it is not reported in the registry record.

The record also does not provide a confidence interval for the treatment-group comparison, the analysis population, missing-data procedures, or a complete statistical plan. Those gaps matter when assessing the precision, robustness, and scope of an inference. The p-value should not be interpreted as the probability that the result is due to chance, nor does it establish the clinical importance of the observed data.

In general, a randomized comparison can help estimate differences between assigned groups, but interpretation depends on how participants were analyzed, the completeness of outcome data, and the appropriateness of the analysis. The registry identifies the study as randomized and triple-masked, but does not report implementation details. The conclusions that can be drawn from the posted record are therefore limited to the stated group summaries and sponsor-reported statistical comparison, rather than a broader claim about treatment effects or clinical outcomes.

15. Why This Trial Matters Statistically

This trial is statistically notable because the primary outcome is continuous, while the reported comparison is rank-based. The registry provides means and standard deviations to describe each group, but reports the Wilcoxon (Mann-Whitney) test for inferential comparison. This illustrates why descriptive summaries and a test result should not be treated as interchangeable: means describe arithmetic averages, whereas a rank-based test uses the ordering of observations.

The posted group means point in different directions, but the record does not provide a between-group effect estimate with a confidence interval. That distinction matters. A p-value can indicate how the observed data relate to a test’s null model, but it does not supply the size or precision of the treatment contrast. Without an estimate and uncertainty interval, readers cannot directly assess the range of group differences compatible with the data from the registry report.

The outcome also highlights the difference between an imaging endpoint and a patient-reported or functional outcome. The primary measure concerns fibrosis assessed by magnetic resonance imaging at baseline and 1 year. It addresses a structural feature of the heart, not symptoms or how participants felt. This alignment between the endpoint and the stated interest in scarring is clear, but it does not make the endpoint a substitute for other outcomes.

Finally, the record illustrates the limits of interpreting small trial summaries when analysis populations, missing-data handling, and multiplicity procedures are not reported. The posted group counts and event entries provide useful descriptive context, but they do not resolve those methodological questions. Clear reporting of effect estimates, uncertainty, participant flow, and analysis decisions would help readers judge the result more fully.

16. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report a between-group effect estimate or confidence interval for the primary fibrosis comparison. The reported p-value of 0.02 therefore cannot be paired with a registry-reported measure of the magnitude and precision of the contrast. Group means and standard deviations are available, but the method used for the sponsor’s comparison is rank-based, and the underlying participant-level observations are not reported.

The analysis population is not defined, and participant flow or reasons for unavailable measurements are not described. Although the outcome summaries list 11 participants in the losartan group and 9 in the placebo group, the record does not explain how these figures relate to randomized enrollment or whether all participants contributed to the endpoint analysis. Missing-data methods and sensitivity analyses are not reported.

The registry lists left ventricular mass as a secondary outcome but does not provide its result in the registry record. A multiplicity strategy is also not reported, so the relationship between the primary result and the other outcome analyses is unclear. The statistical plan, sample-size justification, interim analyses, and detailed outcome-analysis procedures are not reported in the registry record.

Details of randomization and masking are limited to the labels randomized and triple-masked. The record does not specify the allocation method, who was masked, or how masking was maintained. It does not describe MRI acquisition, measurement, or review procedures in detail. These omissions limit assessment of potential sources of bias and measurement variability.

The safety entries are also limited: serious and other adverse event counts are reported as zero for the listed groups, while death counts are not reported. The record does not provide event terms or additional safety context. Taken together, these limitations mean that the registry supports a focused description of the reported fibrosis summaries and test, but not a comprehensive evaluation of robustness, safety, or broader clinical effects.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy — NCT01150461.
• Registry record last updated 2013-09-05; status last verified 2013-09.
• Results first posted 2013-09-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

20. Record Summary

The registry describes a completed, randomized, triple-masked, parallel phase 2 trial sponsored by Massachusetts General Hospital. It lists enrollment of 20 and compares losartan 50 mg by mouth twice daily with placebo twice daily in nonobstructive hypertrophic cardiomyopathy.

The primary outcome was percentage change from baseline in left ventricular fibrosis at 1 year, assessed by magnetic resonance imaging. The posted means were -23.0 for losartan and 31.0 for placebo. The sponsor-reported Wilcoxon (Mann-Whitney) comparison had p = 0.02. A between-group effect estimate and confidence interval are not reported in the registry record.

The record lists left ventricular mass as a secondary outcome but does not report its result in the registry record. Analysis-population details, missing-data methods, multiplicity procedures, and further statistical-plan information are not reported. Serious and other adverse event entries are 0 in both groups; death counts are not reported.