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 Effect of Indacaterol on Inspiratory Capacity (IC) (NCT01012765), a randomized phase 3 study. The primary outcome is Peak Inspiratory Capacity (IC) After 21 Days of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01012765 |
| Phase | Phase 3 |
| Condition | Chronic Obstructive Pulmonary Disease |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 173 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with moderate chronic obstructive pulmonary disease (COPD) were eligible for the study. The full analysis set included randomized patients who received at least one dose of study medication during at least one study period and had observations after 21 days. The registry record reports enrollment of 173 participants; the primary endpoint reports arm-specific analysis counts of 110 for indacaterol, 106 for placebo, and 105 for tiotropium.
Intervention
Indacaterol was given at 150 μg once daily. Participants received the treatments in three periods, with the order varying by randomized sequence. The study aimed to assess peak inspiratory capacity after 21 days of treatment.
Comparator
The comparators were placebo and open-label tiotropium at 18 μg once daily. The registry describes the study as placebo controlled and identifies tiotropium as an active control.
Primary question
The primary endpoint was peak inspiratory capacity (IC), measured in liters after 21 days of treatment. The registry presents least-squares mean estimates and 95% confidence intervals for each treatment arm. It does not report a treatment-contrast estimate or a test of the differences between treatments, so the posted arm-level results do not directly answer how much the treatments differed.
In a crossover study, participants receive multiple treatments across successive periods, rather than being assigned to remain in one treatment group for the entire study. The six listed sequences vary the order of indacaterol, placebo, and tiotropium. This structure allows treatment responses to be examined within participants, but interpretation depends on the analysis accounting appropriately for the study's period and participant structure. The registry says the primary endpoint analysis used an analysis of variance model with center, period, treatment, and patients within center as factors.
The study also included secondary lung-function outcomes, including trough IC, lung-volume measures, airway resistance, and FEV1. The primary question addressed remains specifically about peak IC after 21 days. The record describes the timing and measurement approach, but does not report a formal estimate of the difference between indacaterol and either comparator.
3. Trial Design
This was a randomized, phase 3, multicenter, three-period crossover study in patients with moderate COPD. The registry reports enrollment of 173 participants and a completed study. The start was recorded as 2009-11 and primary completion as 2011-01. Indacaterol was compared with placebo, with open-label tiotropium included as an active control.
Each participant's treatment order was one of six listed sequences. Across the three treatment periods, the sequences arranged indacaterol 150 μg once daily, placebo once daily, and tiotropium 18 μg once daily in different orders. Indacaterol and placebo were administered using a single-dose dry powder inhaler; the record's arm descriptions identify tiotropium as open label. The registry categorizes masking as quadruple, while also explicitly describing tiotropium as open label. It does not explain how those descriptions applied across treatments or study roles.
The primary endpoint was measured after 21 days of treatment. The primary analysis population was the full analysis set: randomized participants who received at least one dose of study medication during at least one study period and had observations after 21 days. The primary endpoint's analysis counts were 110 for indacaterol, 106 for placebo, and 105 for tiotropium. These are treatment-specific counts and should not be read as the number randomized to separate parallel groups, since the design was crossover.
The registry identifies an analysis of variance model with center, period, treatment, and patients within center as factors. It does not report further details about sequence effects, carryover handling, model assumptions, or the statistical plan. The record also lists seven secondary outcomes in addition to the primary endpoint. The order of treatment periods and the repeated observations within participants are important features of the design; the registry's model description indicates that period and participant structure were considered, but provides limited detail about implementation.
The registry does not report the trial's sample-size justification, planned treatment contrasts, or interim analyses. Enrollment alone therefore does not establish the rationale for the study's size, and the posted arm-level endpoint results cannot be treated as a complete account of the prespecified inferential analysis.
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: 173 participants were screened. 129 participants entered the study.
Treatment Period 1
| Stage | Tiotropium - Placebo - Indacaterol | Indacaterol - Placebo - Tiotropium | Indacaterol - Tiotropium - Placebo | Placebo - Indacaterol - Tiotropium | Placebo - Tiotropium - Indacaterol | Tiotropium - Indacaterol - Placebo |
|---|---|---|---|---|---|---|
| STARTED | 20 | 21 | 23 | 18 | 22 | 25 |
| COMPLETED | 17 | 21 | 21 | 15 | 19 | 25 |
| NOT COMPLETED | 3 | 0 | 2 | 3 | 3 | 0 |
Reasons for not completing this period:
| Reason | Tiotropium - Placebo - Indacaterol | Indacaterol - Placebo - Tiotropium | Indacaterol - Tiotropium - Placebo | Placebo - Indacaterol - Tiotropium | Placebo - Tiotropium - Indacaterol | Tiotropium - Indacaterol - Placebo |
|---|---|---|---|---|---|---|
| Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 | 0 |
| Administrative problems | 0 | 0 | 1 | 1 | 1 | 0 |
| Protocol Violation | 0 | 0 | 0 | 2 | 1 | 0 |
| Unsatisfactory therapeutic effect | 0 | 0 | 0 | 0 | 1 | 0 |
Treatment Period 2
| Stage | Tiotropium - Placebo - Indacaterol | Indacaterol - Placebo - Tiotropium | Indacaterol - Tiotropium - Placebo | Placebo - Indacaterol - Tiotropium | Placebo - Tiotropium - Indacaterol | Tiotropium - Indacaterol - Placebo |
|---|---|---|---|---|---|---|
| STARTED | 17 | 21 | 21 | 15 | 19 | 25 |
| COMPLETED | 16 | 19 | 18 | 15 | 18 | 24 |
| NOT COMPLETED | 1 | 2 | 3 | 0 | 1 | 1 |
Reasons for not completing this period:
| Reason | Tiotropium - Placebo - Indacaterol | Indacaterol - Placebo - Tiotropium | Indacaterol - Tiotropium - Placebo | Placebo - Indacaterol - Tiotropium | Placebo - Tiotropium - Indacaterol | Tiotropium - Indacaterol - Placebo |
|---|---|---|---|---|---|---|
| Withdrawal by Subject | 1 | 0 | 1 | 0 | 1 | 0 |
| Abnormal laboratory value(s) | 0 | 0 | 0 | 0 | 0 | 1 |
| Adverse Event | 0 | 1 | 1 | 0 | 0 | 0 |
| Unsatisfactory therapeutic effect | 0 | 1 | 1 | 0 | 0 | 0 |
Treatment Period 3
| Stage | Tiotropium - Placebo - Indacaterol | Indacaterol - Placebo - Tiotropium | Indacaterol - Tiotropium - Placebo | Placebo - Indacaterol - Tiotropium | Placebo - Tiotropium - Indacaterol | Tiotropium - Indacaterol - Placebo |
|---|---|---|---|---|---|---|
| STARTED | 16 | 19 | 18 | 15 | 18 | 24 |
| COMPLETED | 16 | 19 | 18 | 15 | 18 | 24 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 21 days were included in the analysis.
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.
| Characteristic | Unit | Safety Set |
|---|---|---|
| Participants analysed | 129 | |
| Age, Continuous | years | 61.4 (SD 8.9) |
| Sex: Female, Male: Female | Participants | 42 |
| Sex: Female, Male: Male | Participants | 87 |
6. Primary Endpoint
The registry lists the primary outcome as Peak Inspiratory Capacity (IC) After 21 Days of Treatment, measured over 21 days.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Liters |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was peak inspiratory capacity (IC) after 21 days of treatment, measured in liters. IC is a spirometric measure of the volume of air that can be inhaled from the end of a normal exhalation. It is relevant in COPD because changes in lung volumes can be reflected in the capacity available for inspiration. This endpoint describes lung function; it is not itself a direct measure of symptoms, daily activity, or longer-term clinical outcomes.
The registry says spirometry followed internationally accepted standards. Peak IC was defined using the maximum of the mean across three values measured at 30 minutes, 2 hours, 3 hours, and 4 hours after dosing. The measurements were made by body plethysmography. The brief study description says these post-inhalation time points were included to elucidate peak IC during an approximately 4 hour period.
Using repeated measurements during the hours after dosing can characterize the post-dose peak rather than relying on a single measurement at one time. The endpoint therefore focuses on the highest measured mean across the scheduled post-dose time points, after the treatment period. It is distinct from trough IC, which appears among the secondary outcomes and refers to measurement at a different point in the dosing cycle.
The registry reports least-squares mean estimates with 95% confidence intervals for each treatment arm. Those estimates describe modeled arm-level peak IC. A treatment comparison would ordinarily require an estimated contrast, with uncertainty, between treatments. Such a contrast is not reported in the registry record, so the endpoint estimates alone do not establish the size or precision of a difference between indacaterol and either comparator.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary endpoint estimates are least-squares means for peak IC after 21 days. For indacaterol, the estimate is 2.69 liters, with a 95% confidence interval from 2.64 to 2.75. For placebo, the estimate is 2.48 liters, with a 95% confidence interval from 2.42 to 2.53. For tiotropium, the estimate is 2.63 liters, with a 95% confidence interval from 2.58 to 2.69. The corresponding treatment-specific analysis counts are 110, 106, and 105.
These are arm-level estimates, not reported treatment differences. The registry record does not include a contrast estimate comparing indacaterol with placebo or tiotropium, a confidence interval for either contrast, or a p-value for those comparisons. It would be inappropriate to infer a formal comparative result solely by inspecting the arm means or their confidence intervals. In a crossover design, the treatment comparison should use the within-participant structure and the model's handling of period and center, rather than treating the treatment arms as independent parallel groups.
A confidence interval expresses uncertainty around an estimated quantity under the analysis model. For an arm-level estimate, it gives a range of values compatible with the estimate and its modeled sampling uncertainty. It is not a range containing a specified proportion of individual participants' measurements, and it does not on its own establish whether two treatments differ. For a direct comparison, the relevant interval would be the interval around the contrast itself. That quantity is not reported in the registry record.
The registry describes the primary model as an analysis of variance with center, period, treatment, and patients within center as factors. That is useful context for interpreting the least-squares means, which are model-based estimates rather than simple descriptions of raw measurements. However, the available description does not give the model specification in enough detail to reconstruct the analysis or assess every assumption. In particular, additional details about sequence and carryover effects are not reported in the registry record.
There is no discrepancy flag indicating a conflict between a sponsor analysis and a recalculated result. More importantly, the posted record contains no treatment-contrast analysis to compare with a simple recalculation. No unadjusted contrast or precision measure should be invented from the arm summaries. The descriptive pattern of the three estimates is not a substitute for the trial's inferential comparison.
The study's sample-size planning illustrations, when interpreted, describe hypothetical planning under stated assumptions rather than the study's observed power. The registry record does not report the trial's own sample-size justification. Neither enrollment nor the arm-level confidence intervals establishes whether the trial had adequate precision for a particular treatment contrast.
Overall, the record shows modeled mean peak IC estimates for each treatment, each with a reported 95% confidence interval. It does not show the comparative estimates needed to quantify the evidence for differences between treatments. Interpretation should therefore remain descriptive and endpoint-specific, without extending the result to unreported outcomes or broader clinical conclusions.
9. Statistical Methods Explained
Continuous outcomes, such as peak IC measured in liters, are commonly summarized by a mean or a model-based mean. The registry labels the primary statistic as a least-squares mean. In general, a least-squares mean is a model-based estimate of the average outcome after accounting for terms included in the statistical model. It can differ from a simple arithmetic average when the model adjusts for design factors or when the analysis uses a structured design such as this crossover study.
The record's primary model is described as an analysis of variance with center, period, treatment, and patients within center as factors. In general, including period can account for systematic differences among study periods, while including participant structure can reflect that multiple treatment-period observations come from the same person. Center can account for differences associated with the study centers. The registry does not provide enough detail to determine the exact parameterization, covariance assumptions, or estimation procedure.
What does the confidence interval describe?
The primary endpoint estimates are accompanied by 95% confidence intervals. In general, a confidence interval conveys the uncertainty of an estimated quantity under the model and its assumptions. The reported intervals are for the arm-level least-squares means. They do not directly quantify the uncertainty in a treatment difference. To assess a comparison, the estimate and interval for the relevant contrast would be needed. Those are not reported in the registry record.
Confidence intervals also do not describe the spread of individual participant values. The arm-level interval is uncertainty about a model-based mean, not an interval expected to contain most participants' IC measurements. The registry does not report a standard deviation or another measure of individual-level dispersion for the primary endpoint.
Why does crossover structure matter?
In a crossover design, participants receive more than one treatment, according to an assigned order. This can make within-participant comparisons informative because each participant contributes observations under multiple treatments. It also means that period, treatment order, and possible persistence of an earlier treatment may matter to interpretation. The record lists six treatment sequences and states that period and patients within center were included in the primary analysis model. It does not report whether sequence or carryover effects were assessed, nor does it describe washout periods. These details are not reported in the registry record.
For general statistical interpretation, treating the three treatment-specific counts as independent parallel groups would disregard the crossover structure. A direct analysis should use the design and its participant-level repeated observations. Because only arm-level summaries are posted, the within-participant covariance and the pairing of observations cannot be recovered from the endpoint estimates alone.
What can and cannot be inferred from arm summaries?
The reported means describe the modeled endpoint level in each treatment condition. A contrast would express the estimated difference between conditions and would have its own uncertainty. Arm means and their individual confidence intervals do not provide all the information required to reconstruct that contrast in a crossover study. The registry does not post a contrast, standard error for a contrast, confidence interval for a contrast, or p-value for the primary treatment comparisons.
General statistical practice distinguishes a descriptive estimate from a hypothesis test. A test addresses a specified comparison under a statistical model; a confidence interval for that comparison communicates both direction and precision. Without the comparison result, the arm-level estimates should not be used to claim statistical significance or to quantify the comparative effect.
What do the planning illustrations mean?
Sample-size illustrations based on an observed effect are planning exercises, not observed trial outcomes and not observed power. General planning calculations depend on assumptions about the target effect, significance level, allocation, and statistical approximation. The stated assumptions for these illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect described as a fraction of the observed effect. They are not the trial's own design justification, which is not reported in the registry record.
Such illustrations are hypothetical: they indicate participant counts under the selected assumptions, not the probability that this completed study detected an effect. Observed power is not a useful substitute for the estimate and its confidence interval. The registry provides no trial-specific sample-size rationale, and any planning figures should not be read as evidence that the study had a particular probability of finding a treatment difference.
Why does over-dispersion matter in general?
Over-dispersion is a general concern for outcomes whose variability is greater than a statistical model expects. If present and not accommodated, standard errors may be too small and confidence intervals too narrow. The primary endpoint is continuous, and the registry record does not report an over-dispersion assessment. This general concept does not establish that over-dispersion occurred in this trial. Assessment would require the underlying data and model diagnostics, which are not reported in the registry record.
The endpoint is defined from repeated post-dose measurements, and its analysis uses a model with stated design factors. The record does not supply enough information to independently verify assumptions or reproduce the primary analysis. Accordingly, the posted least-squares means and confidence intervals can be described as reported, while unreported comparison statistics and model details should remain unknown.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome, peak IC after 21 days, and seven secondary outcomes. The secondary outcomes cover trough IC, lung-volume measures, airway resistance, and FEV1 at specified time points. Testing multiple outcomes or multiple treatment contrasts can increase the chance of at least one apparently unusual finding if no multiplicity strategy is used. In general, a prespecified multiplicity plan can define how such testing is interpreted or adjusted.
The multiplicity strategy is not reported in the registry record. The record also does not report the planned hierarchy among secondary outcomes, whether all listed outcomes were intended for formal hypothesis testing, or any adjustment across the treatment comparisons. The number of analyses recorded is zero, and no inferential results for the listed comparisons are posted. Therefore, no conclusion about multiplicity-adjusted evidence can be drawn.
Missing-data handling is also not described in detail. The primary population is defined as randomized participants who received at least one dose during at least one study period and had observations after 21 days. This definition identifies who could be included, but does not explain how missing endpoint observations, incomplete periods, or participants with only some treatment-period data were handled. Imputation methods, sensitivity analyses, and reasons for missingness are not reported in the registry record.
The analysis counts differ by treatment condition, but the registry does not explain those differences. In a crossover study, a participant may contribute outcome data for one treatment period without contributing data for every treatment period. The posted counts alone do not show how much within-participant information was available or whether the analysis used all eligible observations in a particular model.
The primary population definition and the stated analysis model provide useful context, but they do not replace details about missing data or multiplicity. These unknowns limit independent assessment of the precision and robustness of any comparative inference, especially because the registry does not post treatment-contrast 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 |
|---|---|---|---|
| Indacaterol 150ug | 1 | 118 | 0.8% |
| Placebo | 1 | 120 | 0.8% |
| Tiotropium 18ug | 3 | 119 | 2.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Indacaterol 150ug | 20 of 118 |
| Placebo | 16 of 120 |
| Tiotropium 18ug | 10 of 119 |
Most frequent serious adverse event terms
| Event term | Organ system | Indacaterol 150ug | Placebo | Tiotropium 18ug |
|---|---|---|---|---|
| LUNG DISORDER | Respiratory, thoracic and mediastinal disorders | 0 of 118 | 1 of 120 | 1 of 119 |
| PNEUMONIA | Infections and infestations | 0 of 118 | 0 of 120 | 1 of 119 |
| HAND FRACTURE | Injury, poisoning and procedural complications | 1 of 118 | 0 of 120 | 0 of 119 |
| INJURY | Injury, poisoning and procedural complications | 0 of 118 | 0 of 120 | 1 of 119 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Indacaterol 150ug | Placebo | Tiotropium 18ug |
|---|---|---|---|---|
| NASOPHARYNGITIS | Infections and infestations | 9 of 118 | 8 of 120 | 3 of 119 |
| BACK PAIN | Musculoskeletal and connective tissue disorders | 2 of 118 | 2 of 120 | 5 of 119 |
| HEADACHE | Nervous system disorders | 2 of 118 | 3 of 120 | 2 of 119 |
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | 3 of 118 | 2 of 120 | 1 of 119 |
| COUGH | Respiratory, thoracic and mediastinal disorders | 4 of 118 | 0 of 120 | 0 of 119 |
| RHINITIS | Infections and infestations | 2 of 118 | 0 of 120 | 0 of 119 |
| HYPOTENSION | Vascular disorders | 0 of 118 | 2 of 120 | 0 of 119 |
Serious events with the highest arm-level rate: hand fracture (0.8%), pneumonia (0.8%), injury (0.8%), lung disorder (0.8%).
The registry reports serious adverse event counts for each treatment condition: 1 among 118 at risk for indacaterol 150ug, 1 among 120 for placebo, and 3 among 119 for tiotropium 18ug. These are counts during the reported safety observation, not estimates of comparative risk adjusted for the crossover design. The record does not provide a statistical comparison of serious adverse events between treatments.
The registry also lists four serious-event terms with a reported frequency of 0.8% each: HAND FRACTURE, PNEUMONIA, INJURY, and LUNG DISORDER. It does not identify those terms by treatment condition in the listed terms, so they should not be assigned to a particular treatment based on this record. The count of participants with other adverse events was 20 among 118 for indacaterol, 16 among 120 for placebo, and 10 among 119 for tiotropium.
The safety groups' at-risk counts differ from the primary endpoint analysis counts. These figures have different stated roles and should not be combined or treated as interchangeable. The registry does not report deaths for these groups, so death counts are not reported in the registry record. Event counts are descriptive and do not, by themselves, establish whether treatments differ in safety.
12. What the Result Does, and Does Not, Mean
The primary endpoint results describe least-squares mean peak IC after 21 days for each treatment condition. The registry reports 2.69 liters for indacaterol, 2.48 liters for placebo, and 2.63 liters for tiotropium, with a 95% confidence interval for each estimate. These are model-based arm summaries. Their meaning is limited to peak IC as defined and measured in the trial.
The posted results do not quantify the difference between indacaterol and placebo or between indacaterol and tiotropium. No comparison estimate, confidence interval for a comparison, or p-value is reported. Accordingly, the arm summaries do not establish a statistically significant treatment difference, nor do they establish equivalence or lack of difference. In a crossover study, the paired treatment information and model structure are relevant to those questions, and they cannot be reconstructed from the arm summaries alone.
The endpoint is a physiological measure and should not be conflated with symptoms, exacerbations, quality of life, or other clinical outcomes. Although the registry lists secondary measures of lung function, it does not report results for those outcomes in the record described. The peak IC result therefore cannot be extended to outcomes that are unreported.
The registry's analysis population includes participants with observations after 21 days and who received at least one dose during at least one period. The record does not provide detailed missing-data methods or sensitivity analyses. Its primary model description identifies center, period, treatment, and patients within center, but does not report enough detail to fully evaluate model assumptions or reproduce the analysis.
Safety counts are also descriptive. They show the reported number of participants with serious and other adverse events in each treatment condition, but no comparative safety analysis is posted. Those counts should be considered separately from the primary endpoint results.
In general, a clinical trial result is best read through its estimated treatment contrast, uncertainty, analysis population, and design. Here, the registry supplies arm-level primary estimates and intervals but not the formal contrasts. The record supports a description of those estimates and their precision as arm-level quantities; it does not support a definitive comparative claim about treatment effects.
13. Why This Trial Matters Statistically
This trial illustrates why study design and the form of a reported statistic matter. In a crossover study, each participant can receive multiple treatments in a sequence. The comparison is therefore tied to within-participant information and to factors such as period. The registry identifies a model that includes treatment, period, center, and patients within center, indicating that the analysis was not described as a simple comparison of independent parallel groups.
The posted primary results are least-squares means with 95% confidence intervals for each treatment condition. These are useful for understanding the modeled endpoint level and its uncertainty, but they are not a substitute for treatment contrasts. Without a contrast estimate and its interval, the magnitude and precision of the treatment comparison remain unavailable in the registry record. This distinction is important even when arm estimates appear different.
The study also provides an example of how endpoint definition shapes interpretation. Peak IC was based on repeated post-dose spirometric measurements, with the maximum of the mean across scheduled times used as the endpoint. That definition focuses on a particular aspect of lung function during the post-dose period, rather than on a single measurement or a broader clinical outcome.
Finally, the record distinguishes enrollment from analysis counts and safety counts. Those quantities refer to different populations and purposes, especially in a crossover trial where participants may contribute data across treatment periods. The absence of the sample-size rationale, detailed missing-data methods, multiplicity plan, and treatment-contrast results shows why registry summaries should be read with attention to what is reported and what remains unspecified.
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 limitation for comparative interpretation is that the registry posts arm-level least-squares mean peak IC estimates but no treatment-contrast estimates. No confidence interval or p-value for the primary comparisons is reported in the registry record. It is therefore not possible to quantify the reported comparative effect from these results alone.
Further details of the crossover analysis are limited. The record lists six treatment sequences and says the model included center, period, treatment, and patients within center. It does not report how sequence effects or carryover were assessed, whether a washout period was used, or the exact model specification. These details are not reported in the registry record.
The primary analysis population is defined, and treatment-specific counts are posted, but the record does not explain why the counts differ or how incomplete treatment periods and missing observations were handled. Imputation, sensitivity analyses, and missingness reasons are not reported in the registry record. The multiplicity strategy for the primary and secondary outcomes is also not reported.
The record provides no trial-specific sample-size justification. The primary endpoint summaries do not include a measure of individual-level dispersion, and no detailed model diagnostics are reported. The study is described as quadruple masked while tiotropium is explicitly described as open label; the record does not clarify the masking arrangements. Finally, the safety figures are counts without comparative analysis, and deaths are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of Indacaterol on Inspiratory Capacity (IC) — NCT01012765.
- Registry record last updated 2016-02-17; status last verified 2016-02.
- Results first posted 2012-02-17.
- 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
NCT01012765 is a completed, randomized, phase 3, multicenter, three-period crossover study of indacaterol, placebo, and open-label tiotropium in patients with moderate COPD. The registry reports enrollment of 173 participants. The primary endpoint was peak IC in liters after 21 days, based on post-dose measurements at 30 minutes, 2 hours, 3 hours, and 4 hours.
The registry reports least-squares mean peak IC estimates with 95% confidence intervals for indacaterol, placebo, and tiotropium. It describes an analysis of variance model with center, period, treatment, and patients within center. It does not report direct treatment contrasts or their uncertainty. Seven secondary outcomes are listed, but their results are not reported in the registry record.
Serious and other adverse event counts are reported by treatment condition, without a comparative safety analysis. The record does not report the trial's sample-size justification, detailed missing-data handling, multiplicity strategy, or interim analyses.