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 Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT00876694), a randomized phase 3 study. The primary outcome is The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00876694 |
| Phase | Phase 3 |
| Condition | Chronic Obstructive Pulmonary Disease (COPD) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 186 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Japanese patients with moderate to severe chronic obstructive pulmonary disease (COPD) were the intended study population. The primary endpoint’s stated safety population included patients who received at least one dose of study drug. Further eligibility details are not reported in the registry record.
Intervention
Indacaterol 300 µg was given once a day using a single-dose dry powder inhaler. Daily inhaled corticosteroid monotherapy, if needed, was allowed to remain stable during the study, and salbutamol was available for rescue use.
Comparator
Salmeterol 50 µg was given twice a day using Diskus®. The same stated provisions applied for stable daily inhaled corticosteroid monotherapy, if needed, and access to salbutamol for rescue use.
Primary question
The primary endpoint counted participants with a newly occurring or worsening clinically notable pulse rate at any time after baseline during 52 weeks of treatment. The registry record does not report the endpoint count by treatment group or a statistical comparison between groups.
3. Trial Design
This was a Phase 3, randomized, multi-center, open-label, parallel-group study comparing indacaterol with salmeterol in Japanese patients with COPD. The official title describes a 52-week treatment period and identifies salmeterol as the active control. The study status is completed. Its stated enrollment was 186.
The study’s stated purpose was to collect long-term safety data for indacaterol 300 µg in Japanese patients with moderate to severe COPD. The brief summary says that data were intended for indacaterol registration in Japan. The registry record lists trough forced expiratory volume in one second (FEV1) after 12, 24 and 52 weeks as a secondary outcome. It lists seven outcome measures overall.
Randomization means that assignment to a treatment group is determined by chance rather than solely by a clinician’s or participant’s choice. In general, this can reduce systematic differences between groups at the start of a study, although it does not guarantee that groups will be identical. The registry record does not describe the randomization sequence, concealment of assignment, or the allocation ratio.
The study was open label, with no masking reported. Participants and study personnel therefore were not described as blinded to the assigned treatment. This design feature is relevant when interpreting outcomes that may be influenced by knowledge of treatment, though the registry record does not say whether the pulse-rate endpoint was assessed independently or by a blinded reviewer.
The group descriptions specify different dosing schedules and delivery devices. They also state that stable daily inhaled corticosteroid monotherapy, if needed, was allowed and that salbutamol was available for rescue use in both groups. Further details about treatment adherence, discontinuations, protocol deviations, or follow-up after treatment are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Indacaterol 300 μg | Salmeterol 50 μg |
|---|---|---|
| STARTED | 125 | 61 |
| COMPLETED | 104 | 49 |
| NOT COMPLETED | 21 | 12 |
Reasons for not completing this period:
| Reason | Indacaterol 300 μg | Salmeterol 50 μg |
|---|---|---|
| Adverse Event | 10 | 7 |
| Subject withdrew consent | 6 | 4 |
| Unsatisfactory therapeutic effect | 2 | 0 |
| Abnormal test procedure result(s) | 1 | 0 |
| Administrative problems | 1 | 1 |
| Death | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The safety population included all patients who received at least one dose of study drug.
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 | Indacaterol 300 μg | Salmeterol 50 μg | Total |
|---|---|---|---|---|
| Participants analysed | 125 | 61 | 186 | |
| Age Continuous | years | 70 (SD 7.81) | 67.3 (SD 8.05) | 69.1 (SD 7.97) |
| Sex: Female, Male: Female | Participants | 9 | 1 | 10 |
| Sex: Female, Male: Male | Participants | 116 | 60 | 176 |
6. Primary Endpoint
The registry lists the primary outcome as The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment, measured over 52 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the number of participants with a newly occurring or worsening clinically notable pulse rate during 52 weeks of treatment. It covered measurements at any time after baseline, rather than a single scheduled visit. The registry definition included low and high pulse-rate criteria, with thresholds and changes from baseline specified in beats per minute.
Low pulse rate was defined as a value <40 bpm, or a value <=50 bpm together with a decrease from baseline >=15 bpm. High pulse rate was defined as a value >130 bpm, or a value >=120 bpm together with an increase from baseline >=15 bpm. A qualifying measurement could therefore be based on an absolute threshold alone or on a threshold paired with a specified change from baseline.
Counting participants with an event is a binary-outcome approach: each participant is classified according to whether the defined event occurred, and the result can be expressed as a count. This endpoint is used to monitor a specified safety feature over the treatment period. The registry record does not report the number meeting the definition in either treatment group, nor does it give an effect estimate or uncertainty interval. It is therefore not possible to describe the comparative result from this endpoint using the recorded information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint and its definition, but does not report primary endpoint results by treatment group. No comparative estimate, confidence interval, or p-value for this outcome is reported. The record also lists zero analyses. As a result, the posted information does not establish the direction or precision of a treatment-group difference for clinically notable pulse rate.
This absence of a reported comparison is distinct from evidence that the groups had the same outcome. A statistical comparison requires information about the observed outcomes and, ordinarily, a method for quantifying uncertainty. Neither is available for the primary endpoint in the registry record. The endpoint definition alone specifies what would be counted; it does not indicate how often it occurred.
The primary outcome is a participant count, not a continuous measure of pulse rate. It combines low and high pulse-rate criteria and includes both newly occurring and worsening events. Without group-level counts or a breakdown by type of event, the record does not show which criterion, if any, contributed to an outcome. Nor does it report the timing, duration, recurrence, or clinical consequences of qualifying measurements.
The listed safety data provide some separate descriptive information. For serious adverse events, the registry lists 16 affected participants among 125 at risk in the indacaterol group and 4 among 61 at risk in the salmeterol group. For other adverse events, it lists 61 affected participants among 125 at risk in the indacaterol group and 26 among 61 at risk in the salmeterol group. These are posted counts, not a reported adjusted comparison. The record does not give an inferential analysis or uncertainty interval for them. They also do not substitute for the missing primary pulse-rate result.
General statistical interpretation: an estimate describes the observed contrast between groups, while a confidence interval describes the range of values compatible with the data and the method used. A narrow interval would indicate greater precision than a wide interval, but neither precision nor a treatment contrast can be assessed without the relevant estimate and interval. Statistical significance, if reported, would also not by itself describe clinical importance.
The study was randomized and used an active control, but those design features do not resolve the reporting gap. Random allocation can support fair comparisons when outcomes and analyses are available. Open-label conduct can matter for some kinds of outcome assessment, and the registry record does not provide additional information about blinding of endpoint assessment. The posted information supports a description of the design and outcome definitions, not a conclusion about comparative efficacy or safety for the primary endpoint.
9. Statistical Methods Explained
The primary outcome is described as a number of participants, and its meaning is participants with an event. In general, this is a binary endpoint: a participant either meets the defined event criteria during the observation period or does not. The reported count is a direct summary of how many participants met those criteria. A count alone, however, does not give the uncertainty around the result or a comparison between treatment groups.
For this outcome, an event could be low or high pulse rate under the stated threshold rules. A low value qualified at <40 bpm, or at <=50 bpm when accompanied by a decrease from baseline >=15 bpm. A high value qualified at >130 bpm, or at >=120 bpm when accompanied by an increase from baseline >=15 bpm. The endpoint also included newly occurring or worsening findings after baseline. These rules define the outcome; they do not indicate how observations were handled when measurements were missing or how worsening was operationalized beyond the description in the registry record.
General explanation: a treatment comparison for a binary endpoint can be expressed in different ways, such as a difference in event frequency or a relative measure. Each effect measure answers a somewhat different question. A comparison should be accompanied by an uncertainty interval and interpreted in relation to the study design and outcome definition. The registry record does not report a primary-endpoint effect estimate, an interval, or a p-value, so no such comparison can be interpreted for this study.
Randomization assigns treatment by chance. In general, it aims to make treatment groups comparable with respect to both measured and unmeasured baseline characteristics, on average across repeated randomizations. It cannot ensure exact balance in a particular trial. The record identifies the study as randomized but does not report the sequence-generation method, allocation concealment, stratification, or allocation ratio. Equal allocation is stated as an assumption for the planning illustration, not as a reported feature of the actual trial allocation.
The parallel-group design means participants were assigned to a treatment group rather than described as switching between treatments. The study is also identified as open label, meaning masking was not used. In general, knowledge of assignment can affect treatment behavior, reporting, or some forms of outcome assessment. The endpoint uses pulse-rate measurements, but details about measurement procedures and independent assessment are not reported in the registry record. It would be inappropriate to assume specific safeguards or biases without those details.
The study describes a 52-week treatment period, and the primary endpoint considers findings at any time after baseline over that period. A measure covering any time during follow-up can capture an event that is not present at a scheduled endpoint visit. It may also depend on how often measurements are taken and how incomplete follow-up is handled. Measurement frequency, event adjudication, and detailed follow-up procedures are not reported in the registry record.
General explanation: multiple outcomes or multiple analyses can raise multiplicity concerns. When many hypotheses are tested, the chance of at least one apparently noteworthy result can increase if each is assessed without an adjustment. Appropriate interpretation depends on which outcomes were prespecified, which analyses were conducted, and whether an adjustment or hierarchy was used. The record lists seven outcome measures and zero analyses, but does not report a statistical plan, multiplicity procedure, or analysis results. It is therefore not possible to determine how multiplicity was handled.
The registry record identifies a safety population for the primary outcome: patients who received at least one dose of study drug. This is not necessarily the same as every participant enrolled or randomized. In general, analysis populations need to be defined because exclusions, treatment discontinuation, and missing measurements can affect the data included in an estimate. Further analysis-population definitions, participant flow, and missing-data methods are not reported in the registry record.
The sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between treatment groups, and a normal approximation. The planned effect to detect is described as a stated fraction of the observed effect. For a binary outcome, such assumptions are used in general to illustrate the amount of information that might be needed to detect a specified effect under a chosen model. Such an illustration is not an observed trial result, does not establish the study’s original design rationale, and is not observed power. The registry record does not report the trial’s own sample-size justification or statistical plan.
A confidence interval is a way of expressing uncertainty around an estimate under a statistical model and its assumptions. In general, it reflects both the observed data and the precision available from the study. A p-value addresses compatibility between data and a specified null hypothesis under the analysis assumptions; it does not measure the size or clinical importance of an effect. Neither type of inferential result is reported for the primary endpoint in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists seven outcome measures, including the primary pulse-rate endpoint and a secondary outcome of trough FEV1 after 12, 24 and 52 weeks. It reports zero analyses. No multiplicity adjustment, testing hierarchy, or prespecified statistical plan is described. Without those details and without reported analyses, it is not possible to assess how the study addressed the possibility of chance findings across multiple outcomes or time points.
The primary endpoint is defined for the safety population, which included all patients who received at least one dose of study drug. Further analysis populations are not reported in the registry record. The record does not explain how participants who stopped treatment, missed visits, or lacked pulse-rate measurements were handled. It also does not report the amount or pattern of missing outcome data, or any imputation or sensitivity analysis.
In general, missingness can affect the interpretation of an outcome when participants with unavailable measurements differ from those with observed measurements. The implications depend on why data are missing and on the analysis method. Without information on completeness and handling, the effect of missing data cannot be evaluated for this endpoint.
The record does not report whether interim analyses were planned or conducted. It also does not provide details of an analysis population beyond the primary safety-population definition. These omissions limit assessment of how the reported enrollment, follow-up, and outcome definitions would connect to a formal treatment comparison.
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 300 μg | 16 | 125 | 12.8% |
| Salmeterol 50 μg | 4 | 61 | 6.6% |
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 |
|---|---|
| Indacaterol 300 μg | 61 of 125 |
| Salmeterol 50 μg | 26 of 61 |
Most frequent serious adverse event terms
| Event term | Organ system | Indacaterol 300 μg | Salmeterol 50 μg |
|---|---|---|---|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 3 of 125 | 1 of 61 |
| Pneumonia | Infections and infestations | 3 of 125 | 0 of 61 |
| Angina pectoris | Cardiac disorders | 1 of 125 | 0 of 61 |
| Retinal haemorrhage | Eye disorders | 0 of 125 | 1 of 61 |
| Uveitis | Eye disorders | 0 of 125 | 1 of 61 |
| Colonic polyp | Gastrointestinal disorders | 1 of 125 | 0 of 61 |
| Sudden death | General disorders | 1 of 125 | 0 of 61 |
| Appendicitis | Infections and infestations | 1 of 125 | 0 of 61 |
| Bronchitis | Infections and infestations | 1 of 125 | 0 of 61 |
| Herpes zoster | Infections and infestations | 1 of 125 | 0 of 61 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Indacaterol 300 μg | Salmeterol 50 μg |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 34 of 125 | 13 of 61 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 26 of 125 | 14 of 61 |
| Cough | Respiratory, thoracic and mediastinal disorders | 14 of 125 | 0 of 61 |
| Upper respiratory tract infection | Infections and infestations | 8 of 125 | 3 of 61 |
| Bronchitis | Infections and infestations | 5 of 125 | 4 of 61 |
Serious events with the highest arm-level rate: pneumonia (2.4%), chronic obstructive pulmonary disease (2.4%), retinal haemorrhage (1.6%), uveitis (1.6%), cerebral infarction (1.6%).
The registry lists serious adverse-event counts by group. In the indacaterol group, 16 participants were affected among 125 at risk; in the salmeterol group, 4 participants were affected among 61 at risk. For other adverse events, the listed counts are 61 among 125 at risk with indacaterol and 26 among 61 at risk with salmeterol. These are descriptive counts as recorded, not an adjusted comparison or a complete account of event timing and severity.
The registry also lists serious adverse-event terms with percentages: pneumonia, 2.4%; chronic obstructive pulmonary disease, 2.4%; retinal haemorrhage, 1.6%; uveitis, 1.6%; cerebral infarction, 1.6%; and angina pectoris, 0.8%. The denominator and calculation details for these percentages are not reported in the registry record, so they should not be used to infer group-specific risks or comparative effects.
Deaths are not reported in the adverse-event figures. The listed serious-event terms and counts do not establish causation or provide a complete account of the safety profile. The record does not report statistical comparisons or uncertainty intervals for these figures.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of indacaterol 300 µg once a day and salmeterol 50 µg twice a day over 52 weeks in Japanese patients with COPD. It identifies a primary safety endpoint based on newly occurring or worsening clinically notable pulse rate. This allows readers to understand what the study intended to count, but the record does not report the primary outcome by treatment group or a statistical comparison.
Accordingly, the posted information does not show whether the groups differed on the primary endpoint, how large any difference was, or how precisely it was estimated. It does not support a conclusion that either treatment was safer or more effective. The listed serious and other adverse-event counts are descriptive safety information and do not replace an analysis of the primary endpoint.
The record also identifies trough FEV1 as a secondary outcome at specified follow-up times, but does not report its results. The study’s stated purpose concerned collection of long-term safety data, with data intended for registration in Japan. That purpose describes the study context; it is not itself evidence of a particular clinical result.
General explanation: results from a trial are most informative when the outcome definition, analysis population, group-level findings, effect estimate, and uncertainty are reported together. A clear definition helps explain what was measured; a comparison and its uncertainty help show what the data can support. In this case, the design and definitions are recorded, but the primary comparative results and relevant inferential details are not.
The described study applies to its specified population, treatments, and follow-up period. Further eligibility criteria and detailed analysis methods are not reported in the registry record. The information should therefore be read as a record of the study design and selected safety counts, not as a complete quantitative account of the comparative effects of the treatments.
13. Why This Trial Matters Statistically
This study is statistically notable for distinguishing a defined safety endpoint from a reported treatment effect. The registry gives detailed rules for what counted as clinically notable pulse rate, including absolute thresholds and changes from baseline. Those rules make the intended endpoint more interpretable than an undefined label, but they cannot show how often the event occurred or whether the groups differed.
The randomized, parallel-group design and active control identify the intended structure of the comparison. The 52-week treatment period and the endpoint’s coverage of any time after baseline also define the follow-up context. At the same time, the open-label design is relevant when considering possible influences on outcome measurement or care, and the record does not describe blinded endpoint assessment.
The study’s stated safety purpose and the posted adverse-event counts are useful context, but the primary endpoint results and analysis are not reported. This highlights why a registry entry’s design information and outcome definitions should not be mistaken for a complete results report. A statistical conclusion requires observed group outcomes and a method for describing uncertainty.
More broadly, the record illustrates the importance of reporting analysis populations, missing-data handling, multiplicity procedures, and the prespecified statistical approach. Those details help readers judge the reliability and scope of a comparison. They are not reported, so conclusions must remain limited to the design and descriptive information that is recorded.
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 primary limitation for interpreting the main question is that the registry record does not report the primary endpoint count by treatment group or a comparative estimate. It also does not report a confidence interval or p-value for that endpoint. Consequently, the direction, magnitude, and precision of a primary treatment difference cannot be assessed.
The study was open label, with no masking reported. The registry record does not say whether pulse-rate assessments were reviewed independently or by assessors unaware of treatment assignment. It also does not provide detailed measurement schedules, event adjudication procedures, or how recurrent findings were handled.
Although a safety population is defined as patients who received at least one dose, participant flow and further analysis-population definitions are not reported. The record does not describe missing outcome data, discontinuations, protocol deviations, or methods used to address incomplete follow-up. These omissions limit assessment of how the observed data would represent the intended study population.
The record lists seven outcome measures but zero analyses. It does not report a multiplicity approach, a statistical plan, interim-analysis information, or the trial’s own sample-size justification. The stated planning assumptions describe an illustration, not the original design rationale or observed power.
The safety figures are descriptive, and the record does not report comparative uncertainty for them. The denominator details for the listed serious-event percentages are not reported. Finally, the study concerns Japanese patients with COPD under the specified treatment regimens and 52-week follow-up; further eligibility details are not reported in the registry record. Generalization beyond that described context cannot be assessed from the recorded information alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) — NCT00876694.
- Registry record last updated 2011-11-08; status last verified 2011-10.
- Results first posted 2011-11-08.
- 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
NCT00876694 is a completed Phase 3 randomized, open-label, parallel-group study of indacaterol 300 µg once a day versus salmeterol 50 µg twice a day in Japanese patients with COPD. The official title describes multi-center treatment over 52 weeks, and the stated enrollment is 186. The study’s stated purpose was to collect long-term safety data for indacaterol.
The primary outcome counted participants with a newly occurring or worsening clinically notable pulse rate after baseline. The record defines low- and high-pulse-rate thresholds but does not report group-specific results or a statistical comparison. Trough FEV1 after 12, 24 and 52 weeks is listed as a secondary outcome. The record lists serious and other adverse-event counts, but does not provide inferential comparisons for those figures.
Further statistical methods, missing-data handling, and analysis details are not reported in the registry record. The available information supports description of the trial design, endpoint definition, and selected safety counts, but not a comparative conclusion about the primary endpoint.