This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Efficacy of Doxycycline in Patients With Non-Ischemic Cardiomyopathy (NCT01935622), a randomized phase 2 study. The primary outcome is Peak Aerobic Exercise Capacity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01935622 |
| Phase | Phase 2 |
| Condition | Non-ischemic Cardiomyopathy, Systolic Heart Failure (NYHA II-III) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 10 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Virginia Commonwealth University |
| Results posted | Yes |
2. Clinical Question
The clinical question was whether doxycycline, given to people with stable heart failure and non-ischemic cardiomyopathy, would be associated with a change in peak aerobic exercise capacity over 14 days. The registered primary outcome was interval change in peak VO2, measured during a cardiopulmonary test. The trial description also mentions ventilatory efficiency as an intended measure, but the registry record lists no posted outcome measure for it.
The population was described as patients with non-ischemic cardiomyopathy and systolic heart failure, NYHA II-III. The registry record does not provide further eligibility details or a reported analysis population. It does not state how participants were selected beyond the condition description, or whether the posted results include everyone enrolled.
Participants were assigned to Doxycycline 100 mg, Doxycycline 20 mg, or placebo. The two doxycycline regimens are described as twice daily for 14 days; the placebo description does not specify a duration. The record does not state a direct treatment contrast, such as a prespecified comparison of either dose with placebo, and no comparative analysis is posted.
In practical statistical terms, the record leaves the main question unanswered: it identifies the outcome and treatment groups, but reports no group medians, interquartile ranges, effect estimate, or uncertainty measure. Thus, the posted results do not establish the size or direction of any change or difference in peak VO2.
3. Trial Design
This was a Phase II, randomized, quadruple-masked, parallel study sponsored by Virginia Commonwealth University. The registry record gives enrollment as 10 and lists the study status as terminated. The recorded study start is 2012-07, and primary completion is listed as 2014-06. The reason for termination is not reported in the registry record.
The three arms were Doxycycline 100 mg, Doxycycline 20 mg, and placebo. Both doxycycline regimens are described as twice daily for 14 days. The placebo arm is described only as placebo; its dosing schedule and treatment duration are not reported in the registry record. The arm counts are 3 for Doxycycline 100 mg, 3 for Doxycycline 20 mg, and 4 for placebo.
Random allocation can reduce systematic differences between groups at the start of a trial, while masking is intended to limit the influence of treatment knowledge on care, measurement, or assessment. Those are general design principles; the registry record does not identify which roles were included in quadruple masking or describe the allocation procedure. It also does not report details such as allocation concealment or any protocol changes.
A parallel design assigns participants to a group that receives its allocated intervention rather than describing a crossover between treatments. Here, the record lists three parallel arms, but does not state which pairwise comparisons were prespecified or how the three-arm structure was handled in the analysis. No statistical analysis is posted, so the actual comparison strategy cannot be determined from 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
| Stage | Doxycycline 100 mg | Doxycycline 20 mg | Placebo |
|---|---|---|---|
| STARTED | 3 | 3 | 4 |
| COMPLETED | 1 | 1 | 4 |
| NOT COMPLETED | 2 | 2 | 0 |
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: (No data analysis conducted. Insufficient enrollment)
| Characteristic | Unit | Doxycycline 100 mg | Doxycycline 20 mg | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 4 | 10 | |
| Age, Continuous | years | 52 (48 to 55) | 58 (55 to 59) | 54 (49 to 60) | 54 (48 to 60) |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 | 3 | 4 | 10 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 2 | 2 |
| Sex: Female, Male: Male | Participants | 3 | 3 | 2 | 8 |
| Region of Enrollment: United States | participants | 3 | 3 | 4 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Peak Aerobic Exercise Capacity, measured over 14 days.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is interval change in peak VO2 measured during a cardiopulmonary test, with a timeframe of 14 days. Peak VO2 refers to oxygen uptake at the peak of an exercise test. As a general measure, it is used to characterize aerobic exercise capacity; the trial description identifies it as an outcome of interest for people with non-ischemic cardiomyopathy and stable heart failure.
The registry specifies that this outcome should be summarized by the median and interquartile range. A median describes the middle of an ordered set of observations, while the interquartile range describes the spread of the middle portion. These summaries can be useful when a distribution is skewed or when a few observations might strongly affect a mean. They do not, by themselves, quantify a treatment difference or its precision.
The outcome values, medians, and interquartile ranges are missing from the posted results. Consequently, readers cannot determine the direction or size of the interval change from the registry record, compare the groups, or assess how variable the observed measurements were. The record also does not define the precise calculation used for interval change or provide the cardiopulmonary test protocol.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary outcome but does not report its numerical results. For each arm, the listed outcome value and spread are missing. There is therefore no posted median change in peak VO2, no interquartile range, and no numerical comparison between doxycycline and placebo or between the two doxycycline regimens.
The record also lists no analyses. It does not provide an effect estimate, confidence interval, test statistic, or p-value. This means the posted results cannot establish whether the groups differed, how large a difference might have been, or how precisely any difference was estimated. These omissions are especially important for a small study: group counts are 3, 3, and 4, so any observed values would represent limited information about the corresponding groups. No precision estimate is available to show how uncertain a treatment contrast might be.
The record describes the primary endpoint as interval change, but does not report the underlying measurements or explain how the change was derived. It is not possible to assess whether participants had complete paired measurements, how missing measurements were handled, or whether the analysis used the intended population. Those details are not reported in the registry record.
The word “terminated” describes the recorded study status, but does not explain why the trial ended. The reason is not reported in the registry record, and it should not be inferred from the absence of outcome results. Nor does the record establish that the study ended because of safety, lack of effect, recruitment difficulty, or any other particular cause.
The safety figures are also limited. The registry lists 0 serious adverse events in each arm. Other adverse events are listed as 0 for Doxycycline 100 mg, 1 for Doxycycline 20 mg, and 0 for placebo. These are descriptive counts in the posted record, not comparative estimates of risk. Death counts are not reported in the registry record. The small arm counts and missing outcome results prevent a broad assessment of either efficacy or safety.
Overall, the record documents the design, treatment groups, and intended primary measure, but it does not answer the comparative exercise-capacity question. This is a statement about what the posted results contain, not evidence for or against a treatment effect.
9. Statistical Methods Explained
The registry record names a median and interquartile range as the summary approach for the primary outcome. It does not report the actual summaries or any inferential analysis. The explanations below describe general statistical concepts and distinguish them from what can be established for this trial.
What does the median describe?
In general, the median is the central observation after measurements are ordered. It is less affected by unusually high or low observations than the arithmetic mean. The interquartile range describes the spread of the middle portion of the observations and gives a sense of their variability. Reporting both can be informative when the distribution is not well represented by a mean and standard deviation.
For this study, the record specifies median and interquartile range for interval change in peak VO2, but none of those values are posted. A reader therefore cannot judge the observed distribution, compare its center across arms, or see whether the measurements were tightly or widely spread. The specified summaries are descriptive; they are not a test of whether a treatment effect exists.
How would a treatment contrast be interpreted?
In general, a treatment contrast compares an outcome between groups and estimates the size and direction of a difference. A confidence interval, when reported, gives a range of values compatible with the data under the analysis assumptions and indicates the precision of the estimate. It is not a guarantee that the true effect lies in that range. A p-value, when reported, describes the compatibility of the observed data with a specified null model; it is not the probability that a treatment works or that the null hypothesis is true.
No contrast, confidence interval, or p-value is reported in the registry record. The listed arms also mean there are several possible comparisons, but the record does not state which were planned or whether the primary question was framed as a particular dose versus placebo. It would be inappropriate to construct a new comparison from the absent outcome summaries.
Why do small groups affect precision?
As a general principle, estimates based on fewer observations tend to be less precise, all else being equal. Randomization helps guard against systematic differences in expectation, but it cannot ensure that small groups will be balanced on every prognostic feature. Here, the recorded group counts are 3, 3, and 4. Because outcome values and uncertainty estimates are absent, readers cannot quantify the degree of imprecision or assess the balance of measured characteristics.
Over-dispersion is a general issue that arises when outcome variability is greater than a chosen statistical model expects. A model that understates variability can produce uncertainty estimates that are too narrow. This registry record does not report a model, distributional assessment, or variance estimate, so there is no basis for assessing over-dispersion in the trial analysis.
What can be inferred from the planning note?
The registry’s planning note describes hypothetical sample-size illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Such calculations are planning illustrations for a future design, not observed power and not evidence that the current study had a particular probability of detecting an effect.
The record does not include an estimable two-arm comparison for this endpoint, and no numerical planning result is reported in the registry record for interpretation. The trial itself has three arms and the recorded arm counts are unequal. The planning assumptions therefore should not be mistaken for the trial’s design or treated as an analysis of its results. The record does not report a sample-size justification for the trial itself.
What analysis details are absent?
The registry lists no analyses. It does not report a statistical test, a model, covariate adjustment, a method for handling missing observations, or a defined analysis population. It also does not report whether the primary outcome was analyzed as a change score, whether baseline measurements were adjusted for, or whether any sensitivity analyses were conducted. These methods cannot be reconstructed from the endpoint description alone.
Randomization, masking, and the choice of a median summary describe features of the design or reporting, not the full analysis plan. Without reported outcome data and analysis methods, no recalculated estimate can be made and no independent check of a sponsor analysis is possible. The registry record does not report a sponsor analysis for this endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure, the interval change in peak VO2, and no posted secondary outcomes. It also lists no analyses. The record does not report a multiplicity procedure or explain how the primary outcome was prioritized relative to the ventilatory-efficiency aim mentioned in the study description.
In general, multiplicity arises when several outcomes, treatment contrasts, time points, or analysis choices are tested. Conducting many tests can increase the chance of a nominally unusual result even when there is no true effect. Researchers may address this by prespecifying a primary comparison, adjusting inference, or treating additional analyses as exploratory. These are general approaches; the registry record does not say which, if any, were used.
Missing-data handling is also not reported in the registry record. The record does not state how many participants had a peak VO2 measurement at the relevant time, whether any baseline or follow-up observations were unavailable, or whether participants were excluded from an analysis. It does not describe imputation, complete-case analysis, or sensitivity analyses. The absence of posted outcome summaries makes it impossible to distinguish unavailable measurements from measurements that were collected but not reported.
The analysis population is not reported in the registry record. In general, an intention-to-treat analysis retains participants in their randomized groups, while other analysis populations can apply different eligibility or adherence rules. No particular approach should be attributed to this trial without a reported analysis plan or results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Doxycycline 100 mg | 0 | 3 | 0.0% |
| Doxycycline 20 mg | 0 | 3 | 0.0% |
| Placebo | 0 | 4 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Doxycycline 100 mg | 0 of 3 |
| Doxycycline 20 mg | 1 of 3 |
| Placebo | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Doxycycline 100 mg | Doxycycline 20 mg | Placebo |
|---|---|---|---|---|
| Hypotension | Cardiac disorders | 0 of 3 | 1 of 3 | 0 of 4 |
The registry lists serious adverse event counts of 0 in the Doxycycline 100 mg arm, 0 in the Doxycycline 20 mg arm, and 0 in the placebo arm. The corresponding numbers at risk are 3, 3, and 4. These are the serious-event figures recorded for the groups; the registry does not provide serious-event terms in the posted record.
Zero recorded serious events does not establish that the treatments are free of serious risks. With these small group counts, the absence of a recorded event is limited information about the kinds or frequency of events that might occur beyond the study. It also does not resolve whether all safety events were captured or how they were assessed, since those details are not reported in the registry record.
The record separately lists other adverse events: 0 for Doxycycline 100 mg, 1 for Doxycycline 20 mg, and 0 for placebo. These counts should not be combined with the serious-event figures; they are presented as a separate category. Death counts are not reported in the registry record, which is different from a reported count of zero. No comparative safety analysis is posted.
12. What the Result Does, and Does Not, Mean
This record documents a randomized Phase II study intended to assess safety and exercise capacity in people with non-ischemic cardiomyopathy and systolic heart failure. It identifies three treatment groups and specifies interval change in peak VO2 as the primary outcome. These details describe the study question and design, not its efficacy findings.
The primary outcome values and analyses are missing. Therefore, readers cannot determine whether peak VO2 changed within any arm, whether changes differed between groups, or how uncertain a possible difference would be. The registry record does not support a conclusion that doxycycline improved, worsened, or had no effect on exercise capacity. A missing result is not evidence of no effect.
The record does show 0 serious adverse events in each arm and other adverse event counts of 0, 1, and 0 across the listed arms. Those counts are descriptive and come from small groups. They cannot establish comparative safety or rule out uncommon harms. Death counts are not reported in the registry record.
The terminated status is part of the record, but the reason for termination is not reported. It cannot be used on its own to infer the study’s outcome or the reason results are absent. Similarly, the stated planning assumptions do not describe observed power or resolve the missing treatment-effect estimate.
The appropriate interpretation is limited: the registry record shows what was intended and records selected safety counts, but it does not provide the primary outcome results needed to evaluate the comparative exercise-capacity question. Any stronger claim would go beyond the posted information.
13. Why This Trial Matters Statistically
This trial illustrates the difference between registering a clearly named endpoint and reporting enough information to interpret it. The record identifies interval change in peak VO2, the measurement method, and the timeframe. Yet the numerical summaries and analyses are absent. Without them, even a well-defined outcome cannot answer the comparative question for readers.
The design also highlights why the analysis plan matters in a multi-arm study. There are two doxycycline regimens and a placebo group, but no reported analysis explains which contrasts were intended or how multiplicity was considered. A reader cannot infer a prespecified dose comparison from the presence of the arms alone.
The recorded arm counts are 3, 3, and 4. Small groups provide limited information for estimating differences and describing uncommon safety outcomes. Reporting an estimate with an uncertainty measure would be particularly useful for showing what the study can and cannot say, but neither is available for the primary endpoint.
Finally, the terminated status and missing outcome results demonstrate that registry interpretation must distinguish a study’s status from its findings. The record contains design and safety details, but does not explain the termination or report the primary analysis. Statistically, those are separate details: study status cannot substitute for an outcome estimate.
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 most direct limitation is that the primary endpoint has no posted values or spread estimates. Although the record specifies a median and interquartile range, neither is reported for any arm. It also provides no comparative estimate or inferential analysis, so the magnitude, direction, and precision of a treatment difference cannot be assessed.
The recorded group counts are 3, 3, and 4, limiting the amount of information available for group-level description and safety interpretation. The registry record does not report baseline characteristics, so it is not possible to examine whether the randomized groups were similar on measured features. The reason for termination is not reported, and the record does not explain whether termination affected outcome collection or analysis.
The outcome description does not include the precise calculation for interval change, test procedures, or handling of unavailable measurements. The analysis population, missing-data methods, statistical model, and prespecified contrasts are also not reported in the registry record. Ventilatory efficiency is mentioned in the study description, but no corresponding outcome measure or result is posted.
The serious adverse event counts are recorded as 0 in each arm, while deaths are not reported. With the small arm counts and no detailed safety analysis, these records should be interpreted narrowly. The registry record also does not describe the placebo schedule, the roles included in quadruple masking, or the reason the study was terminated.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Doxycycline in Patients With Non-Ischemic Cardiomyopathy — NCT01935622.
- Registry record last updated 2014-08-20; status last verified 2014-08.
- Results first posted 2014-08-20.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a randomized, quadruple-masked, parallel Phase II study of doxycycline in non-ischemic cardiomyopathy. It lists enrollment of 10 and a terminated status. The arms are Doxycycline 100 mg, Doxycycline 20 mg, and placebo; the doxycycline regimens are described as twice daily for 14 days.
The primary outcome is interval change in peak VO2 measured during a cardiopulmonary test, with a 14-day timeframe and planned summaries of median and interquartile range. Outcome values and analyses are not posted. Serious adverse event counts are 0 in each arm; other adverse event counts are 0, 1, and 0 across the arms. Death counts and the reason for termination are not reported in the registry record.