Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy (NCT00879060), a randomized phase 4 study. The primary outcome is Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo..

2. Clinical Question

3. Trial Design

This was a phase 4, randomized, quadruple-masked, parallel-group trial sponsored by Tufts Medical Center. The registry lists 53 participants with HCM as randomized. It describes an experimental spironolactone group and a placebo control group. The registry record says baseline demographic, clinical, and structural variables were well matched. It does not report the randomization method, allocation concealment procedures, or the identities of the groups included in the masking.

The primary outcome concerned change in serum markers of collagen turnover from baseline to 12 months. The registry also lists measures of functional capacity, heart-failure symptoms, diastolic function, and cardiac mass and fibrosis assessed by cardiac magnetic resonance imaging. The listed imaging measures include percentage of left ventricular mass, maximum left ventricular wall thickness, left ventricular end-diastolic cavity size, and left atrial dimension. The record lists 8 outcome measures and 11 analyses.

The registry gives a start date of 2007-11, a primary completion date of 2011-11, and a status of completed. The planned treatment period for the primary question was 12 months. The registry record does not report the overall study completion date separately from primary completion, nor does it describe enrollment progress or participant flow. The results shown in the record are insufficient to determine how many participants completed follow-up or contributed data to each outcome. Numerical primary outcome estimates and a detailed 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

Analysis population for the primary outcome, as defined in the registry: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.

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.

Population: 53 HCM patients (41 +/- 13 years old, 72% men and 28% female) were randomized 1:1 to receive either 50mg of spironolactone or a placebo pill over a 12 month follow up period.

6. Primary Endpoint

The registry lists the primary outcome as Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo., measured over The time points measured were at Baseline and at 12 Months (Follow-Up)..

The primary endpoint concerns absolute change in serum markers of collagen turnover, expressed in micrograms/L, over a one-year follow-up period in the spironolactone group compared with placebo. The record identifies PINP and PIIINP as markers of collagen synthesis and ICTP as a marker of collagen degradation. Measurements were taken at baseline and at 12 months.

These markers were selected to assess collagen turnover in the context of myocardial fibrosis. The registry’s background describes fibrosis as part of pathological remodeling in HCM and proposes that circulating collagen-turnover markers can reflect myocardial fibrosis. This explains the biological rationale for measuring the markers; it does not by itself show that a marker is a direct measure of fibrosis in each participant or that a change in a marker corresponds to a change in clinical status.

The endpoint description says a two-sample t-test was used to compare markers at baseline and absolute differences in change from baseline to 12 months. The registry lists several marker categories rather than one numerical summary. The primary endpoint values, between-group estimates, measures of precision, and associated test results are not reported in the registry record. As a result, the posted record does not show the observed magnitude or direction of change in any marker.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, quadruple-masked, parallel-group design, with spironolactone compared with placebo. These design features define how the comparison was intended to be organized, but the record does not supply procedural details such as the randomization sequence, allocation concealment, or the groups included in masking. The listed trial status is completed.

What does the two-sample t-test compare?

The primary outcome description names a two-sample t-test. In general, this test compares the mean of a continuous measure between two groups. Here, the registry says it was used for baseline comparisons of collagen-turnover markers and for absolute differences in change from baseline to 12 months. A treatment comparison based on change asks how the groups’ measured changes differ, rather than treating a single follow-up measurement as the only information. The registry does not provide the resulting group means, estimated differences, standard deviations, confidence intervals, or p-values.

General statistical context: a conventional t-test relies on assumptions about independent observations and the distribution of the data, especially when samples are small. The test can be sensitive to skewed data or influential observations. The record does not report checks of these assumptions, transformations, or alternative analyses. It also does not describe whether any covariates were included; the named test is a two-sample t-test.

Why measure baseline and follow-up?

The primary description gives measurements at baseline and 12 months. General statistical context: baseline measurements can characterize the starting values and help define change over time. A change score is calculated for each participant by comparing follow-up with baseline, and the study can then compare these changes between randomized groups. The registry specifically describes absolute differences in change from baseline to follow-up. It does not explain the handling of participants who lack either measurement, or whether the analysis used any additional adjustment.

The record names multiple markers: PINP and PIIINP for collagen synthesis, and ICTP for collagen degradation. These measures represent different aspects of collagen turnover and should not be treated as interchangeable. The record does not identify one marker as the sole result that summarizes the others, and it does not provide numerical results for any of them.

How should uncertainty be read?

General statistical context: an estimate is more informative when presented with a measure of uncertainty. A confidence interval gives a range of estimates compatible with the observed data and the specified method. Wider intervals indicate less precision than narrower intervals, though interpretation also depends on the outcome and study context. A p-value alone does not tell readers how large a difference is or whether the estimate is precise. Because the registry record does not report numerical estimates or intervals for the primary outcome, this page cannot assess precision from the posted results.

What do the planning illustrations represent?

The posted planning assumptions describe a normal approximation, a two-sided significance level of 0.05, and equal allocation between the arms. The effect to detect is framed as a stated fraction of the observed effect. For continuous outcomes, the displayed planning quantities are participants per arm for 80% power and for 90% power. General statistical context: such calculations show the sample size that would be needed under specified assumptions; they do not measure the power actually achieved in a completed trial. The registry record does not report a protocol-based sample-size justification, and the planning illustrations should not be interpreted as observed power.

The assumptions also say that sample-size calculations are based on an observed effect. However, the numerical primary outcome estimates needed to inspect that effect are not reported in the registry record. The illustrations therefore cannot replace the missing outcome reporting or establish how precisely this trial estimated the treatment contrast.

What remains unclear about the analysis?

The registry lists 8 outcome measures and 11 analyses, while the primary outcome encompasses several marker categories and time points. The statistical plan, including any prespecified hierarchy, multiplicity adjustment, model specification, missing-data method, or sensitivity analysis, is not reported in the registry record. These omissions limit assessment of how the recorded analyses relate to the original study question. The posted record does identify a test and measurement schedule, but it does not provide enough detail to reproduce the analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 11 analyses. The primary outcome includes several collagen-turnover markers and more than one time point. The registry record itself notes that the primary outcome has several categories or time points and is not reduced to one comparison. This matters because multiple outcomes or comparisons can create more opportunities for apparently notable results. General statistical context: multiplicity procedures can help control the chance of false-positive findings across a family of tests, but the appropriate approach depends on the prespecified questions and analysis plan.

Whether the investigators used an adjustment, a hierarchy of outcomes, or another strategy to address multiple comparisons is not reported in the registry record. The record also does not identify a single primary marker result among PINP, PIIINP, and ICTP or explain how any results across markers were to be summarized. Without the results and analysis plan, readers cannot determine how multiple comparisons were handled or how to interpret any individual test in relation to the overall question.

Missing-data procedures and analysis populations are also not reported in the registry record. It does not say how many randomized participants contributed measurements at each visit, how incomplete follow-up was handled, or whether analyses followed an intention-to-treat, per-protocol, or other population definition. These details matter because analysis of only participants with complete measurements can differ from analysis of all randomized participants, especially if missingness is related to outcomes or treatment. The available record does not permit evaluation of that possibility.

11. 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 1% reporting threshold.

The adverse-event table lists 26 participants at risk in the spironolactone group and 27 in the control group. It records 0 serious adverse events and 0 other adverse events in each group, and 0 deaths in each group. These are the counts shown in the registry record; they are not evidence that no adverse events occurred outside the table’s reporting scope.

General statistical context: a zero count in a trial does not prove that an event is impossible or that a treatment has no safety risks. The interpretation depends on the number of participants observed, the length and completeness of follow-up, how events were defined, and how they were collected. The registry record does not provide details of event definitions, ascertainment procedures, or participant follow-up for safety. The listed at-risk counts should therefore be read as the context for the posted counts, not as a complete characterization of safety.

The table contains no listed serious-event terms. The record does not provide additional narrative on adverse events, severity, timing, or reasons for discontinuation. These figures summarize what is posted and should not be extended beyond that reporting.

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

This trial addresses a defined statistical question: whether serum markers of collagen turnover changed differently over a 12-month period in the spironolactone group compared with placebo among people with HCM. The registry describes randomization, masking, the two study groups, measurement timing, and a two-sample t-test. It also lists other clinical and imaging outcomes. Those elements describe the scope and intended comparison, not the observed treatment effect.

The key limitation for interpretation is that numerical primary outcome results are not reported in the registry record. Without group values and an estimate of the between-group difference, readers cannot tell whether the markers increased or decreased, how large the difference was, or how uncertain it was. The record also does not report the detailed results for the listed secondary outcomes. No conclusion about treatment benefit, lack of benefit, or clinical relevance follows from the design description alone.

General statistical context: a biomarker outcome and a clinical outcome answer different questions. A change in a serum marker may be informative about a biological process, but it does not automatically establish a change in symptoms, functional capacity, cardiac structure, or other outcomes. This study listed measures in those areas, but their numerical results are not reported in the registry record.

The sample-size illustrations elsewhere on the page are planning scenarios and are not observed power. The record does not report the protocol’s sample-size justification, and the numerical results needed to judge precision are absent. The adverse-event table reports zero events in the listed categories among the participants at risk, but those counts alone do not establish the absence of risk.

13. Why This Trial Matters Statistically

Statistically, the trial is notable for pairing a randomized, masked comparison with a primary question about multiple biological markers. The design identifies the central contrast—spironolactone versus placebo—and the measurement schedule at baseline and 12 months. The record also places this question alongside functional, symptom, echocardiographic, and cardiac magnetic resonance outcomes. This makes clear that the study aimed to examine more than one aspect of HCM.

The registry also illustrates why an endpoint description is not enough to interpret a trial. It names markers, units, time points, and a statistical test, but does not report numerical outcome estimates. Without the actual estimates and their uncertainty, readers cannot assess effect direction, magnitude, or precision. A clear design can make a question understandable while leaving the evidence needed to answer it unavailable in the record.

The number of outcomes and analyses raises questions about how results were prioritized and how multiplicity was addressed. Those details are not reported in the registry record. The sample-size illustrations make a further distinction important: planning calculations are conditional on assumptions and are not evidence of the precision achieved in a completed trial.

Finally, the posted safety counts show how a zero-event table should be read in context. The counts are informative as a record of what was reported, but do not demonstrate that no risk exists. Together, these features make the record a useful example of the difference between trial design, statistical reporting, and the conclusions that numerical results can support.

14. 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 main trial-specific limitation of the registry record is the absence of numerical primary outcome results. Although the record names the collagen-turnover markers, their units, measurement times, and the stated test, it does not report group means, changes, between-group estimates, variability, confidence intervals, or p-values. The direction, magnitude, and precision of the primary comparison therefore cannot be assessed.

The registry lists several marker categories and multiple outcome measures, but the analysis plan for prioritizing or combining them is not reported in the registry record. With 8 outcome measures and 11 analyses, the absence of information about prespecified comparisons and multiplicity procedures limits interpretation of any individual result. The record also does not describe analysis populations, missing-data handling, or the number of participants with available measurements at each time point.

Further design and implementation details are not reported in the registry record, including the method of sequence generation, allocation concealment, masking procedures, adherence, and participant flow. The intervention description is incomplete, so the full dosing and adjustment protocol cannot be reconstructed from the record. Although baseline variables are described as well matched, that does not resolve the absence of follow-up data or detailed methods.

The record reports zero serious and other adverse events and zero deaths in the listed groups, but provides no event definitions, collection procedures, or fuller safety narrative. These limitations concern the information available in the registry record; they do not establish that the trial itself lacked further analyses or documentation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy — NCT00879060.
• Registry record last updated 2021-04-27; status last verified 2021-03.
• Results first posted 2021-04-27.
• 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.

18. Record Summary

This completed phase 4 trial, sponsored by Tufts Medical Center, randomized 53 people with HCM to spironolactone or placebo. It is listed as quadruple-masked and parallel-group, with a 12-month treatment and follow-up period for the primary question. The registry reports a mean age of 41 +/- 13 years and 72% male, and states that demographic, clinical, and structural characteristics were well matched at baseline.

The primary outcome concerned absolute change in serum collagen-turnover markers, including PINP, PIIINP, and ICTP, from baseline to 12 months. A two-sample t-test is named in the outcome description. The record lists 8 outcome measures and 11 analyses, but numerical primary and secondary outcome results, detailed analysis populations, and missing-data methods are not reported in the registry record.

The adverse-event table records zero serious events, zero other events, and zero deaths in both listed groups. These counts describe the posted safety table and do not establish absence of risk.