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 Study to Evaluate the Effect of Ranolazine and Dronedarone When Given Alone and in Combination in Patients With Paroxysmal Atrial Fibrillation (NCT01522651), a randomized phase 2 study. The primary outcome is Atrial Fibrillation Burden (AFB) at Baseline.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01522651 |
| Phase | Phase 2 |
| Condition | Atrial Fibrillation |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 134 |
| Arms in the primary outcome | 5 |
| Lead sponsor | Gilead Sciences |
| Results posted | Yes |
2. Clinical Question
Population
Participants with paroxysmal atrial fibrillation were eligible for this study. The registry describes the analysis population as randomized participants who received at least one dose of study drug and had at least 2 weeks (14 days) of atrial fibrillation burden data both from screening to Day 1 and after treatment began. Participants with available data were analyzed. The registry record does not provide further eligibility details in the information summarized for this outcome.
Intervention
The study evaluated ranolazine and low-dose dronedarone, given alone or together, over 12 weeks. The posted groups included ranolazine 750 mg alone, dronedarone 225 mg alone, ranolazine 750 mg with dronedarone 225 mg, and ranolazine 750 mg with dronedarone 150 mg. Each active regimen was compared within the trial against a placebo group receiving ranolazine placebo plus dronedarone placebo.
Comparator
The comparator was placebo for both study drugs: ranolazine placebo plus dronedarone placebo for 12 weeks. The record describes a randomized, double-blind, parallel-group design. It does not report the methods used to generate the allocation sequence or to conceal allocation.
Primary question
The study objective was to evaluate the effect of ranolazine and low-dose dronedarone, alone and in combination at different dose levels, on atrial fibrillation burden over 12 weeks. Atrial fibrillation burden is the total time in atrial tachycardia or atrial fibrillation expressed as a percentage of total recording time. However, the posted primary outcome is labeled atrial fibrillation burden at baseline. Those baseline summaries describe the groups before treatment-related change can be assessed; they do not, by themselves, answer whether burden changed during treatment or differed between regimens after treatment.
3. Trial Design
This was a phase 2, proof-of-concept, randomized, placebo-controlled, double-blind, parallel-group study sponsored by Gilead Sciences. The registry lists atrial fibrillation as the condition and an enrollment of 134. The study is marked completed. Its recorded start date is 2012-01-24, and its primary completion date is 2014-03-10. These registry-level dates describe the study record; they do not establish when individual participants entered or completed treatment.
Five treatment groups are described. The placebo group received ranolazine placebo plus dronedarone placebo. The active groups received ranolazine 750 mg alone, dronedarone 225 mg alone, ranolazine 750 mg with dronedarone 225 mg, or ranolazine 750 mg with dronedarone 150 mg. The planned treatment period described in the arm information was 12 weeks. The parallel-group structure means participants were assigned to a regimen rather than crossing through multiple regimens, while double masking indicates that the study was recorded as double-blind. Details of who was masked are not reported in the registry record.
The registry’s posted primary outcome is baseline atrial fibrillation burden, summarized by treatment group. The outcome analysis population is narrower than the overall enrollment description: it includes randomized participants who received at least one dose and met the specified atrial fibrillation burden data requirements. The baseline group summaries report analysis counts of 18.0 for placebo, 18.0 for ranolazine 750 mg, 23.0 for dronedarone 225 mg, 20.0 for ranolazine 750 mg plus dronedarone 225 mg, and 22.0 for ranolazine 750 mg plus dronedarone 150 mg. These are counts associated with this outcome, not a replacement for the registry’s overall enrollment figure.
The registry record does not report the randomization procedure, allocation concealment process, or the intended statistical model for comparing post-treatment outcomes. The record’s posted baseline endpoint values should therefore be read as descriptive group summaries, not as evidence of a treatment effect.
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.
Before assignment: 327 participants were screened.
Overall Study
| Stage | Placebo | Ranolazine 750 mg | Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 150 mg |
|---|---|---|---|---|---|
| STARTED | 26 | 27 | 26 | 28 | 27 |
| COMPLETED | 17 | 19 | 22 | 20 | 21 |
| NOT COMPLETED | 9 | 8 | 4 | 8 | 6 |
Reasons for not completing this period:
| Reason | Placebo | Ranolazine 750 mg | Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 150 mg |
|---|---|---|---|---|---|
| Adverse Event | 3 | 4 | 4 | 5 | 4 |
| Cardioversion | 1 | 0 | 0 | 0 | 0 |
| Device Malfunction | 0 | 1 | 0 | 0 | 0 |
| Investigator's Discretion | 0 | 1 | 0 | 0 | 0 |
| Protocol Violation | 3 | 0 | 0 | 0 | 0 |
| Reason Not Specified | 0 | 0 | 0 | 1 | 0 |
| Participant Non-Compliance | 1 | 0 | 0 | 0 | 0 |
| Withdrew Consent | 1 | 1 | 0 | 1 | 1 |
| Randomized but Never Treated | 0 | 1 | 0 | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set included randomized participants who received ≥ 1 dose of study drug (ranolazine, dronedarone, or placebo) and had ≥ 2 weeks (14 days) of AFB data for both the period from screening to Day 1 and following the start of treatment. Participants with available data were analyzed.
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: The Safety Analysis Set included participants who received ≥ 1 dose of study drug (ranolazine/placebo tablets or dronedarone/placebo capsules).
| Characteristic | Unit | Placebo | Ranolazine 750 mg | Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 150 mg | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 26 | 26 | 26 | 27 | 26 | 131 | |
| Age, Continuous | years | 72 (SD 8.4) | 70 (SD 10.8) | 75 (SD 7.8) | 71 (SD 7.1) | 73 (SD 9.4) | 72 (SD 8.8) |
| Sex: Female, Male: Female | Participants | 13 | 16 | 16 | 12 | 11 | 68 |
| Sex: Female, Male: Male | Participants | 13 | 10 | 10 | 15 | 15 | 63 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 0 | 0 | 3 | 1 | 6 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 22 | 25 | 26 | 24 | 25 | 122 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 1 | 0 | 0 | 0 | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 26 | 26 | 26 | 27 | 25 | 130 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: Germany | participants | 5 | 4 | 8 | 4 | 2 | 23 |
| Region of Enrollment: Israel | participants | 5 | 6 | 1 | 6 | 6 | 24 |
| Region of Enrollment: Italy | participants | 0 | 0 | 0 | 1 | 0 | 1 |
| Region of Enrollment: Netherlands | participants | 0 | 0 | 0 | 0 | 1 | 1 |
| Region of Enrollment: Poland | participants | 10 | 12 | 11 | 11 | 15 | 59 |
| Region of Enrollment: United States | participants | 6 | 4 | 6 | 5 | 2 | 23 |
6. Primary Endpoint
The registry lists the primary outcome as Atrial Fibrillation Burden (AFB) at Baseline, measured over Baseline.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Standard Error |
| Unit | Percentage of total recording time |
| Endpoint classification | not reduced to a single comparison |
Atrial fibrillation burden (AFB) measures the amount of recorded time a participant spends in atrial tachycardia or atrial fibrillation, expressed as a percentage of total recording time. The registry defines the primary outcome as AFB at baseline and reports it as a percentage of total recording time. It specifies that the displayed group summary is a geometric mean: the mean of log-transformed AFB values, transformed back to the original scale.
As a general statistical concept, burden measures can describe the extent of a condition over a monitoring period, rather than simply whether an episode occurred. Expressing the time in arrhythmia relative to total recording time also places the measure on a common scale when recording durations vary. Those properties can make a burden measure useful for describing the amount of arrhythmia captured during monitoring. The registry record does not describe the monitoring device, recording schedule, or the handling of incomplete recordings beyond the stated analysis-population criteria.
Because the posted primary outcome is specifically at baseline, its group values characterize the recorded burden before the treatment period is evaluated. Baseline summaries can help describe the groups entering follow-up, but they do not show within-participant change or a between-group treatment contrast. The study objective refers to AFB over 12 weeks of treatment; the registry information summarized for this endpoint does not provide a corresponding post-treatment effect estimate or change-from-baseline result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted baseline geometric mean AFB values are 12.7 for placebo, 10.8 for ranolazine 750 mg, 11.6 for dronedarone 225 mg, 11.7 for ranolazine 750 mg plus dronedarone 225 mg, and 11.7 for ranolazine 750 mg plus dronedarone 150 mg. Each value is expressed as a percentage of total recording time. These summaries describe baseline measurements in the relevant outcome analysis groups; they should not be interpreted as estimates of treatment response.
The reported standard errors are 2.21 for placebo, 2.7 for ranolazine 750 mg, 2.47 for dronedarone 225 mg, 2.4 for ranolazine 750 mg plus dronedarone 225 mg, and 2.04 for ranolazine 750 mg plus dronedarone 150 mg. A standard error describes the precision of an estimated group summary under the statistical approach used. It is not the spread of individual participant values. The record does not provide confidence intervals for these baseline summaries, and the standard errors alone do not establish whether any apparent difference between group values is statistically distinguishable from sampling variation.
It is important to separate the study objective from the specific result posted. The objective concerned AFB during a 12-week treatment period, but the listed primary outcome is AFB at baseline. A baseline value is not a change score, a follow-up value, or an adjusted comparison. The posted baseline figures therefore cannot establish whether any regimen altered AFB, whether one regimen differed from another after treatment, or how precisely a treatment effect was estimated.
The overall enrollment is 134, while the baseline endpoint analysis counts differ across groups. The registry describes an analysis population requiring study-drug exposure and specified AFB data before and after treatment began. Consequently, the outcome counts should be interpreted as the numbers represented in these endpoint summaries, rather than assumed to include every enrolled participant. Reasons for any differences between enrollment and endpoint analysis counts are not reported in the registry record.
The registry also lists a secondary outcome concerning the percentage of participants with at least 30%, at least 50%, or at least 70% reduction from baseline in AFB. The existence of that outcome description does not provide its results. For the information available on the primary baseline endpoint, no treatment-effect estimate, confidence interval, or p-value is posted. The registry record does not report the analysis plan or the method used to compare treatment groups for follow-up AFB. Accordingly, interpretation should remain descriptive and focused on what the baseline summaries measure.
9. Statistical Methods Explained
The main statistical feature of the posted primary outcome is its use of a geometric mean with a standard error. A geometric mean is calculated by transforming observations to the logarithmic scale, calculating their mean there, and transforming that mean back to the original scale. The registry describes the reported value in these terms. This approach is often useful for positive measurements that are right-skewed, because the log transformation can make relative differences and proportional variation more suitable for statistical summaries. That is general statistical context; the registry record does not state why this summary was selected for this study.
A geometric mean is not the ordinary arithmetic average. It gives a central summary on a multiplicative scale, and its interpretation depends on the underlying transformation. A value reported as a percentage remains on the percentage scale after exponentiation, but the summary does not mean every participant had that burden. Nor does it give the range of participant-level measurements. The registry does not report the distribution of individual baseline AFB values, so the amount of participant-to-participant variability cannot be reconstructed from the geometric means alone.
What does the standard error communicate?
The standard error describes uncertainty in an estimated summary, rather than the spread of individual observations. General statistical interpretation treats a smaller standard error, relative to the estimate, as indicating greater precision under the assumptions of the calculation. A standard error is not itself a confidence interval. A confidence interval would express a range of values compatible with the data and a specified confidence procedure. Confidence intervals for the baseline summaries are not reported in the registry record.
The listed standard errors can help readers understand that the estimates have sampling uncertainty, but they do not supply a formal test of differences between arms. Comparing the sizes of separate standard errors is not a substitute for estimating a direct contrast, because a contrast depends on the uncertainty and covariance structure of the quantities being compared. The registry does not report a baseline between-group test or a model-based comparison for this endpoint.
Why can over-dispersion matter?
As a general concept, over-dispersion occurs when the variability in observed data is greater than a chosen statistical model expects. If an analysis assumes less variability than the data contain, standard errors can be too small and inferential results can appear more precise than warranted. A model that allows additional variability may better reflect the data. The registry record does not report a dispersion assessment or a model for these baseline AFB summaries, so it is not possible to say whether over-dispersion was evaluated or how it affected the analysis.
What can be inferred from the baseline summaries?
The values and standard errors describe the recorded baseline group summaries for the endpoint analysis population. They do not estimate a randomized treatment effect because treatment has not yet produced a follow-up contrast in these baseline data. A causal comparison would ordinarily require an outcome measured after treatment, or a change-from-baseline comparison, with an appropriate analysis. The registry’s objective refers to AFB over 12 weeks, but the post-treatment outcome estimate and its inferential details are not reported in the registry record in the material summarized for this endpoint.
The endpoint analysis population is defined by treatment exposure and availability of AFB data for both the screening-to-Day 1 period and after treatment began, with at least 2 weeks (14 days) of data for each specified period. This means the analysis does not simply represent all enrolled participants by definition. The record says participants with available data were analyzed but does not describe an imputation method, a sensitivity analysis for missing data, or how data were handled when a participant did not satisfy the stated requirement.
How should planning illustrations be read?
Sample-size illustrations are planning calculations, not observed trial outcomes and not measures of the trial’s achieved power. The stated calculation assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set as a stated fraction of the observed effect. Such calculations depend on their assumptions and are not a substitute for the study’s own design justification. The registry record does not report the trial’s sample-size justification, and these planning assumptions should not be attributed to the original study design. The record also does not report an observed power analysis.
More broadly, a statistical plan would clarify which endpoint was primary for inferential testing, how treatment contrasts were defined, what model was used, and how missing observations and multiple comparisons were handled. Those details are not reported in the registry record. The methods that can be described with confidence are therefore limited to the specified geometric-mean summary, standard error, outcome definition, and analysis-population criteria.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a secondary outcome measuring the percentage of participants who had at least 30%, at least 50%, or at least 70% reduction from baseline in AFB. The record also reports four outcome measures and ten analyses. The information summarized for the primary endpoint does not specify how the study handled multiple outcome thresholds, treatment groups, or analyses when assessing statistical evidence. A multiplicity adjustment, testing hierarchy, or prespecified strategy is not reported in the registry record. Without those details, the error rate associated with any collection of statistical tests cannot be assessed.
The posted primary result is baseline AFB, rather than a change or follow-up contrast. No p-value or confidence interval for a treatment comparison is reported for this endpoint. The analysis plan, including whether baseline comparisons were intended to be formally tested, is not reported in the registry record. Baseline summaries should therefore be treated as descriptive rather than as evidence from a set of treatment-effect tests.
The registry defines the Full Analysis Set as randomized participants who received at least one dose of ranolazine, dronedarone, or placebo and had at least 2 weeks (14 days) of AFB data for both the period from screening to Day 1 and the period following treatment start. It states that participants with available data were analyzed. The record does not report how many participants lacked required data, why data were unavailable, or whether missing values were imputed. It also does not describe sensitivity analyses for missing data or alternative analysis populations.
Because the endpoint analysis depends on data availability, the posted summaries may not represent every enrolled participant. The registry record does not provide enough detail to determine the potential effect of missing outcome data on the baseline summaries or on any treatment-period result. The handling of missing data in the secondary threshold outcome is also not reported in the registry record.
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 |
|---|---|---|---|
| Placebo | 1 | 26 | 3.8% |
| Ranolazine 750 mg | 7 | 26 | 26.9% |
| Dronedarone 225 mg | 2 | 26 | 7.7% |
| Ranolazine 750 mg + Dronedarone 225 mg | 5 | 27 | 18.5% |
| Ranolazine 750 mg + Dronedarone 150 mg | 1 | 26 | 3.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 26 |
| Ranolazine 750 mg | 0 of 26 |
| Dronedarone 225 mg | 0 of 26 |
| Ranolazine 750 mg + Dronedarone 225 mg | 0 of 27 |
| Ranolazine 750 mg + Dronedarone 150 mg | 0 of 26 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 9 of 26 |
| Ranolazine 750 mg | 15 of 26 |
| Dronedarone 225 mg | 14 of 26 |
| Ranolazine 750 mg + Dronedarone 225 mg | 12 of 27 |
| Ranolazine 750 mg + Dronedarone 150 mg | 14 of 26 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Ranolazine 750 mg | Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 150 mg |
|---|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | 0 of 26 | 3 of 26 | 1 of 26 | 0 of 27 | 1 of 26 |
| International normalised ratio increased | Investigations | 0 of 26 | 1 of 26 | 0 of 26 | 1 of 27 | 0 of 26 |
| Atrial flutter | Cardiac disorders | 1 of 26 | 0 of 26 | 0 of 26 | 0 of 27 | 0 of 26 |
| Cardiac failure congestive | Cardiac disorders | 0 of 26 | 0 of 26 | 1 of 26 | 0 of 27 | 0 of 26 |
| Tachyarrhythmia | Cardiac disorders | 0 of 26 | 0 of 26 | 1 of 26 | 0 of 27 | 0 of 26 |
| Vertigo | Ear and labyrinth disorders | 0 of 26 | 0 of 26 | 0 of 26 | 1 of 27 | 0 of 26 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 0 of 26 | 1 of 26 | 0 of 26 | 0 of 27 | 0 of 26 |
| Chest pain | General disorders | 0 of 26 | 0 of 26 | 0 of 26 | 1 of 27 | 0 of 26 |
| Clostridium difficile colitis | Infections and infestations | 0 of 26 | 0 of 26 | 0 of 26 | 1 of 27 | 0 of 26 |
| Enterococcal bacteraemia | Infections and infestations | 0 of 26 | 0 of 26 | 0 of 26 | 1 of 27 | 0 of 26 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Ranolazine 750 mg | Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 225 mg | Ranolazine 750 mg + Dronedarone 150 mg |
|---|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | 2 of 26 | 0 of 26 | 4 of 26 | 1 of 27 | 2 of 26 |
| Dizziness | Nervous system disorders | 1 of 26 | 3 of 26 | 2 of 26 | 0 of 27 | 2 of 26 |
| Constipation | Gastrointestinal disorders | 0 of 26 | 1 of 26 | 1 of 26 | 1 of 27 | 4 of 26 |
| Nausea | Gastrointestinal disorders | 0 of 26 | 3 of 26 | 1 of 26 | 2 of 27 | 1 of 26 |
| Diarrhoea | Gastrointestinal disorders | 0 of 26 | 2 of 26 | 2 of 26 | 1 of 27 | 1 of 26 |
| Fatigue | General disorders | 0 of 26 | 3 of 26 | 0 of 26 | 2 of 27 | 1 of 26 |
| Urinary tract infection | Infections and infestations | 3 of 26 | 1 of 26 | 2 of 26 | 0 of 27 | 0 of 26 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 26 | 1 of 26 | 2 of 26 | 1 of 27 | 1 of 26 |
| Abdominal pain | Gastrointestinal disorders | 0 of 26 | 0 of 26 | 3 of 26 | 2 of 27 | 0 of 26 |
| Asthenia | General disorders | 2 of 26 | 1 of 26 | 0 of 26 | 0 of 27 | 2 of 26 |
Serious events with the highest arm-level rate: atrial fibrillation (11.5%), atrial flutter (3.8%), cardiac failure congestive (3.8%), tachyarrhythmia (3.8%), gastrointestinal haemorrhage (3.8%).
The adverse-event information reports, by group, the number at risk and the number affected by serious adverse events and by other adverse events. For serious adverse events, the reported at-risk and affected counts are 26 and 1 for placebo, 26 and 7 for ranolazine 750 mg, 26 and 2 for dronedarone 225 mg, 27 and 5 for ranolazine 750 mg plus dronedarone 225 mg, and 26 and 1 for ranolazine 750 mg plus dronedarone 150 mg. The record reports 0 deaths in each group.
For other adverse events, the at-risk and affected counts are 26 and 9 for placebo, 26 and 15 for ranolazine 750 mg, 26 and 14 for dronedarone 225 mg, 27 and 12 for ranolazine 750 mg plus dronedarone 225 mg, and 26 and 14 for ranolazine 750 mg plus dronedarone 150 mg. These are counts as recorded, not percentages calculated from the counts. The record lists serious adverse-event terms including atrial fibrillation at 11.5%, atrial flutter at 3.8%, cardiac failure congestive at 3.8%, tachyarrhythmia at 3.8%, gastrointestinal haemorrhage at 3.8%, and international normalised ratio increased at 3.8%.
These figures describe events recorded in the study; they do not establish that a study drug caused an event. The registry record does not provide the event definitions, timing, duration, severity beyond the serious classification, or group-specific assessment of causality. Counts across event categories should not be added to infer the number of affected participants, because a participant may have experienced more than one event.
12. What the Result Does, and Does Not, Mean
The posted primary outcome helps characterize baseline AFB in the trial’s outcome analysis groups. It gives a geometric mean, in percentage of total recording time, for each listed regimen group, along with a standard error. This is useful descriptive information about the baseline measurements and the precision of the group summaries under the reported method.
It does not show a treatment effect. The listed endpoint is AFB at baseline, whereas the study objective concerns AFB over 12 weeks of treatment. A baseline value does not show whether burden later increased or decreased, whether a change differed between groups, or whether a post-treatment contrast was statistically precise. The registry record does not report a treatment-effect estimate, confidence interval, or p-value for a follow-up comparison in the information summarized for this endpoint.
The randomized, double-blind, placebo-controlled design describes how the study was intended to compare regimens. Randomization can support causal comparisons when an appropriate outcome analysis is reported, but the design label alone cannot turn baseline group summaries into evidence of a treatment effect. The record does not report the detailed analysis plan, so the specific intended method for estimating effects cannot be established from this information.
The registry lists a secondary outcome based on thresholds for reduction from baseline, but the description of that outcome is not a result. Similarly, overall enrollment and outcome-specific analysis counts answer different questions: enrollment describes the study, while the baseline counts identify participants represented in these particular summaries. The record does not explain all differences in data availability or provide missing-data sensitivity analyses.
Thus, the defensible reading is narrow: these data describe baseline burden in the reported groups, not the comparative effect of ranolazine, dronedarone, or their combination during treatment. Safety counts likewise describe recorded events and deaths, not proof of causation or a complete characterization of risk. Conclusions about treatment-period efficacy, precision, and the implications of missing information require results and methods that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically interesting because its clinical objective and its posted primary endpoint are not the same kind of quantity. The objective describes AFB over a 12-week treatment period, while the listed primary outcome is AFB at baseline. Recognizing that distinction is essential: baseline summaries describe the starting measurements, but do not estimate what happened after treatment or the difference between treatment groups.
The study also reports a geometric mean and standard error rather than an arithmetic mean and standard deviation. This illustrates why readers need to identify the summary scale before interpreting a value. A geometric mean is based on log-transformed observations and is returned to the original scale. A standard error expresses uncertainty in the estimated mean, not the range of individual values. These measures answer different questions and should not be used interchangeably.
The registry’s analysis population also highlights the difference between overall enrollment and the participants represented in a particular endpoint. The outcome required treatment exposure and specified AFB data for both periods. Endpoint summaries may therefore have different analysis counts from the overall enrollment figure. Such distinctions matter when evaluating how closely a reported estimate represents the randomized study population.
Finally, the registry lists several regimens and a secondary outcome with multiple reduction thresholds, but the statistical plan and multiplicity approach are not reported. Without the treatment-period estimates, their uncertainty, and the analysis strategy, the baseline data cannot establish comparative efficacy. The case underscores a broader statistical principle: clear endpoint definitions, transparent analysis populations, and complete inferential reporting are necessary to move from descriptive results to reliable treatment comparisons.
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 important limitation for interpreting the primary outcome is that the posted endpoint is baseline AFB, while the study objective concerns AFB during 12 weeks of treatment. The baseline summaries do not provide a treatment-period value, change from baseline, or between-group treatment-effect estimate. The registry record does not report a confidence interval or p-value for such a comparison.
The registry describes a Full Analysis Set requiring at least one dose of study drug and at least 2 weeks (14 days) of AFB data in both the screening-to-Day 1 period and the period after treatment began. This eligibility rule means that outcome summaries depend on data availability. The record does not report reasons for missing data, the number excluded for missing endpoint measurements, an imputation method, or sensitivity analyses. It is therefore not possible to assess how missing observations might influence the posted summaries.
The record reports standard errors but not confidence intervals or individual-level distributions for baseline AFB. It does not describe the measurement device or recording procedures in the information summarized for this endpoint. The statistical analysis plan, including the method for treatment comparisons and handling of multiple outcomes or analyses, is also not reported in the registry record. These gaps limit assessment of the precision and robustness of any treatment-period inference.
The registry lists adverse-event counts, but the summarized information does not provide detail on event timing, duration, severity categories beyond seriousness, or causality assessments. These limitations apply to what can be concluded from the registry record; they do not establish that additional information was unavailable elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Effect of Ranolazine and Dronedarone When Given Alone and in Combination in Patients With Paroxysmal Atrial Fibrillation — NCT01522651.
- Registry record last updated 2020-11-06; status last verified 2020-09.
- Results first posted 2020-11-06.
- 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.
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18. Record Summary
NCT01522651 is a completed phase 2, randomized, double-blind, parallel-group, placebo-controlled study sponsored by Gilead Sciences. It evaluated ranolazine and low-dose dronedarone, alone and in combination, in participants with paroxysmal atrial fibrillation. The registry lists enrollment of 134 and a 12-week treatment period.
The posted primary outcome is baseline atrial fibrillation burden, defined as the percentage of total recording time spent in atrial tachycardia or atrial fibrillation. It is summarized as a geometric mean with a standard error. The reported baseline values describe the outcome analysis groups and do not show a treatment-related change or comparative effect. The analysis population required study-drug exposure and specified AFB data availability before and after treatment began.
The registry lists a secondary reduction-threshold outcome and adverse-event counts, but the statistical analysis plan, multiplicity approach, missing-data methods, and treatment-period effect estimate are not reported in the registry record. Interpretation of the posted primary outcome should therefore remain descriptive.