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 of Safety of Foradil in Patients With Persistent Asthma (NCT01845025), a randomized phase 4 study. The primary outcome is Number of First Occurrence(s) of Any Composite Endpoint Including Asthma-related Hospitalizations, Intubations and Deaths During the Study at 26 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01845025 |
| Phase | Phase 4 |
| Condition | Persistent Asthma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 827 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned adolescents and adults aged 12 years and older with persistent asthma. The primary endpoint population is described as the intent-to-treat population: randomized patients who took at least one dose, or one inhalation, of study medication. The registry record lists an enrollment of 827, but does not give the number in each primary endpoint analysis population.
Intervention
The combination arm received formoterol 12 mcg with fluticasone propionate. The fluticasone propionate dose could be 100 mcg, 250 mcg or 500 mcg, for inhalation. The registry record describes this as formoterol in free combination with an inhaled corticosteroid.
Comparator
The active comparator was fluticasone propionate alone, at 100 mcg, 250 mcg or 500 mcg, with placebo to match formoterol. The comparison therefore concerns adding formoterol to fluticasone propionate versus using fluticasone propionate with matching placebo.
Primary question
The study aimed to assess whether the risk of serious asthma-related events was the same between the groups. The composite included asthma-related hospitalizations, intubations and deaths. Its primary endpoint counted first occurrences of the composite during the study at 26 weeks; the description also says that the event count includes all adjudication-confirmed events and that a patient could experience multiple events. The registry record does not report the primary endpoint results or a numerical comparison between groups.
3. Trial Design
This was a Phase 4, randomized, active-controlled safety study with a parallel-group model and quadruple masking. The planned study period was 26 weeks. The registry record lists enrollment of 827 and describes adolescents and adults with persistent asthma. It records a start in 2013-05, primary completion in 2016-05, and a status of terminated. The reason for termination is not reported in the registry record.
The randomized comparison was formoterol 12 mcg plus fluticasone propionate versus fluticasone propionate with placebo to match formoterol. In both groups, fluticasone propionate could be 100 mcg, 250 mcg or 500 mcg. The design thus focused on the safety comparison associated with adding formoterol to an inhaled corticosteroid, rather than comparing different corticosteroid doses as the principal contrast.
The primary safety endpoint was a composite of asthma-related hospitalizations, asthma-related intubations and asthma-related deaths. The registry describes the endpoint as the number of first occurrences of any composite endpoint during the study at 26 weeks, while also specifying that the event count includes all adjudication-confirmed events and that one patient could experience multiple events. This wording makes it important to distinguish the endpoint’s event count from a simple count of people with at least one event.
The stated primary analysis population was the intent-to-treat population, defined in the record as randomized patients who took at least one dose of study medication. The registry also lists secondary outcomes concerning asthma exacerbations, missed school or work, daily activities, nighttime awakenings, rescue medication use, symptoms, asthma control and unplanned healthcare utilization. Numerical results for these outcomes 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.
Before assignment: 827 actual in the protocol section came from the IRT because 2 patients were randomized twice but only counted once.
Overall Study
| Stage | FOM 12 mcg + FP | Fluticasone Propionate (FP) |
|---|---|---|
| STARTED | 411 | 409 |
| COMPLETED | 326 | 332 |
| NOT COMPLETED | 85 | 77 |
Reasons for not completing this period:
| Reason | FOM 12 mcg + FP | Fluticasone Propionate (FP) |
|---|---|---|
| Adverse Event | 6 | 3 |
| Unsatisfactory therapeutic effect | 4 | 2 |
| Withdrawal by Subject | 48 | 44 |
| Lost to Follow-up | 13 | 13 |
| Administrative problems | 8 | 8 |
| Death | 2 | 0 |
| Protocol deviation | 3 | 6 |
| Missing | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication
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 | FOM 12 mcg + FP | Fluticasone Propionate (FP) | Total |
|---|---|---|---|---|
| Participants analysed | 411 | 409 | 820 | |
| Age, Continuous | years | 44.7 (SD 16.67) | 45.6 (SD 17.02) | 45.2 (SD 16.84) |
| Sex: Female, Male: Female | Participants | 284 | 272 | 556 |
| Sex: Female, Male: Male | Participants | 127 | 137 | 264 |
6. Primary Endpoint
The registry lists the primary outcome as Number of First Occurrence(s) of Any Composite Endpoint Including Asthma-related Hospitalizations, Intubations and Deaths During the Study at 26 Weeks, measured over 26 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | number of occurences |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint combines asthma-related hospitalizations, intubations and deaths into one safety outcome, assessed during the study at 26 weeks. A composite endpoint can bring several clinically serious event types into a single measure. In general, this can make a safety comparison more informative when the separate events are uncommon, but it also means that the overall result depends on which event types occur and how often each contributes.
The registry describes the outcome as the number of first occurrences of any composite endpoint, and says that adjudication-confirmed events are included in the event count. It also notes that a patient could experience multiple events during the study. These details call for care in interpreting the endpoint: a count of events is not automatically the same as a count of participants experiencing an event. The record does not provide the event-type breakdown or the primary endpoint counts by treatment group.
The endpoint was used to address the stated safety question about the combination versus fluticasone propionate alone. The registry record gives the endpoint definition and timeframe, but not a numerical estimate, confidence interval or test result. Consequently, the size and precision of the treatment-group comparison cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the question the study was designed to address, but it does not report numerical results for the primary endpoint. It therefore does not establish, from the information in the record, how many primary composite events occurred in either group, the size of a between-group difference, or the uncertainty around such a difference. The study aim of assessing whether risk was the same is not itself evidence that risks were equal.
The record lists safety figures for serious adverse events separately from the primary endpoint. It reports 10 affected participants among 411 at risk in the formoterol plus fluticasone propionate group and 9 among 409 at risk in the fluticasone propionate group. These figures are not a substitute for the primary endpoint results: serious adverse events are a broader safety reporting category, whereas the primary endpoint is a specific composite of asthma-related hospitalizations, intubations and deaths. The registry does not state that the serious adverse event counts are the primary composite event counts.
The description of the primary endpoint includes an important counting detail. It says that a patient could experience multiple events and that adjudication-confirmed events are included. A participant count and an event count can therefore answer different questions. Without the primary endpoint counts and a clear numerical treatment contrast, it is not possible to determine whether the posted safety figures align with or differ from the primary endpoint findings.
The record also lists secondary outcomes, including asthma exacerbations, symptom-related measures and healthcare utilization. Their presence identifies additional questions the trial intended to examine, but numerical results are not reported in the registry record. No conclusions about those outcomes can be drawn from their names alone.
Terminated is the recorded study status. The reason is not reported in the registry record, so the status does not by itself explain why the study ended or establish that the termination was related to safety, recruitment or any other factor. Overall, the available registry entries support a description of the design and endpoint, but not a quantitative judgment about the primary safety comparison.
9. Statistical Methods Explained
The registry record describes a randomized, active-controlled, quadruple-masked, parallel-group trial. Randomization is intended, in general, to reduce systematic differences between groups at the time of assignment. Masking is intended to limit the influence of knowledge about treatment assignment on participants, clinicians, assessors or other trial personnel, depending on who is masked. The registry gives the masking category but does not specify which roles were included or how masking was maintained.
What does the composite endpoint measure?
The primary outcome combines asthma-related hospitalizations, intubations and deaths. In general, a composite endpoint can capture more than one important event type in a single analysis. This can be useful when individual event types are not frequent, but the combined result may be driven more by the more frequent components. Component-specific results help clarify what contributes to a composite. Such results are not reported in the registry record.
The endpoint description refers to first occurrences of the composite and also says that all adjudication-confirmed events are counted, with the possibility that one patient experiences multiple events. Those statements distinguish the event-counting process from a simple participant-level outcome. A participant-level analysis asks whether each person experienced an event; an event-count analysis records events, including repeated events where the definition allows them. The exact primary analysis method is not reported in the registry record, so the analytic handling of repeated events cannot be specified beyond the endpoint description.
Why does event-count variation matter?
General statistical context: count outcomes can vary more than a simple probability model expects, a feature often called over-dispersion. When over-dispersion is present, an analysis that assumes less variation may give confidence intervals that are too narrow or tests that are too optimistic. Methods designed for count outcomes can account for extra variation, but the choice depends on the data and analysis plan. The registry record does not report a model, dispersion estimate or statistical method for the primary endpoint.
The registry defines an event rate as 100 multiplied by the number of patients with any events divided by the total number of patients in a treatment group. That definition is a participant-based percentage, distinct from a raw count of all events if some patients have multiple events. The posted record does not provide the calculated primary endpoint rates or explain whether they were the principal comparison used in the analysis.
How should uncertainty be assessed?
General statistical context: an estimate describes the observed treatment-group contrast, while a confidence interval describes the range of values compatible with the data and the method used, under its assumptions. A wide interval indicates less precision; an interval that includes values reflecting no difference does not prove equivalence. A claim that two treatments have the same risk ordinarily requires an explicitly defined equivalence or non-inferiority framework and an appropriate margin. The registry record does not report such a margin, a confidence interval, a hypothesis test or an analysis plan. The stated aim to assess whether risk was the same should not be taken as evidence that an equivalence design was used.
General statistical context: a p-value, when reported, measures how compatible the observed data are with a specified null model under the analysis assumptions. It does not measure the probability that the null hypothesis is true, nor does it convey the size or clinical importance of an effect. No primary endpoint p-value is reported in the registry record. Thus, neither statistical significance nor evidence of similarity can be assessed from the primary outcome information available in the record.
What do planning illustrations mean?
Sample-size calculations are planning exercises based on assumptions about the effect to detect, variability, significance level, allocation and analysis method. They are not observed results and do not show the probability that a completed trial has found a true effect. The registry record does not report the trial’s own sample-size justification or statistical design assumptions. Any planning illustration based on an observed effect is a separate calculation and should not be interpreted as the trial’s design rationale or as observed power.
The registry record identifies the intent-to-treat population as randomized patients who took at least one dose. This definition is narrower than a population including everyone randomized, because it requires treatment exposure. The record does not provide participant flow, endpoint-specific denominators or details of how missing outcome information was handled. These omissions limit assessment of how the analyzed population relates to the randomized groups.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, including asthma exacerbations, days of school or work missed, limitations in normal daily activities, nighttime awakenings, rescue medication use, symptom-free days, asthma control and unplanned healthcare utilization. Examining several outcomes can raise a multiplicity issue: in general, the chance of at least one apparently unusual result can increase when many statistical tests are performed. Methods such as a prespecified testing sequence or adjustment can address this, but the analysis plan and any multiplicity procedure are not reported in the registry record.
The record identifies an intent-to-treat population consisting of randomized patients who took at least one dose. It does not describe exclusions after randomization, the number analyzed for each outcome, or whether other analysis populations were used. The number of analyses is recorded as zero, but this does not provide a statistical analysis plan or explain how outcome data were handled.
Missing-data methods can affect estimates when participants lack follow-up measurements or event information. General statistical context: complete-case analysis, imputation and other approaches rely on different assumptions, and conclusions can depend on whether missingness is related to observed or unobserved outcomes. The registry record does not report the extent of missing data, the method used to handle it, or sensitivity analyses. It also does not report interim analyses or stopping rules. These details are not reported in the registry record and should not be inferred from the terminated status.
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 |
|---|---|---|---|
| FOM 12 mcg + FP | 10 | 411 | 2.4% |
| Fluticasone Propionate (FP) | 9 | 409 | 2.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| FOM 12 mcg + FP | 5 of 411 |
| Fluticasone Propionate (FP) | 9 of 409 |
Most frequent serious adverse event terms
| Event term | Organ system | FOM 12 mcg + FP | Fluticasone Propionate (FP) |
|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | 2 of 411 | 2 of 409 |
| Pneumonia | Infections and infestations | 1 of 411 | 1 of 409 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 2 of 411 | 0 of 409 |
| Atrial fibrillation | Cardiac disorders | 1 of 411 | 0 of 409 |
| Cardiac failure congestive | Cardiac disorders | 1 of 411 | 0 of 409 |
| Abdominal pain | Gastrointestinal disorders | 1 of 411 | 0 of 409 |
| Duodenal ulcer | Gastrointestinal disorders | 1 of 411 | 0 of 409 |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | 0 of 411 | 1 of 409 |
| Cellulitis | Infections and infestations | 0 of 411 | 1 of 409 |
| Pneumonia bacterial | Infections and infestations | 1 of 411 | 0 of 409 |
Most frequent non-serious adverse event terms
| Event term | Organ system | FOM 12 mcg + FP | Fluticasone Propionate (FP) |
|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | 5 of 411 | 9 of 409 |
Serious events with the highest arm-level rate: asthma (0.5%), osteoarthritis (0.5%), upper gastrointestinal haemorrhage (0.2%), cellulitis (0.2%), pneumonia (0.2%).
The registry reports serious adverse event figures separately for the two treatment groups. For formoterol plus fluticasone propionate, it lists 10 affected participants among 411 at risk; for fluticasone propionate, it lists 9 affected participants among 409 at risk. The record also reports other adverse event figures of 5 among 411 and 9 among 409, respectively. These are safety listings, not the primary composite endpoint counts.
The serious adverse event terms listed include asthma and osteoarthritis at 0.5%, and upper gastrointestinal haemorrhage, cellulitis, pneumonia and tracheobronchitis at 0.2% each. The record does not provide a group-specific breakdown for these terms in the material describing the event lists. Death counts are not reported in the registry record.
General statistical context: adverse event counts describe events observed and recorded under the trial’s reporting definitions. They do not, by themselves, establish that a treatment caused an event or quantify a causal difference. The serious adverse event figures should not be substituted for the asthma-related hospitalization, intubation and death composite. The registry record does not report numerical results for that primary endpoint.
12. What the Result Does, and Does Not, Mean
The record describes a randomized safety comparison in adolescents and adults with persistent asthma, using formoterol plus fluticasone propionate versus fluticasone propionate with matching placebo. It specifies a 26-week primary safety endpoint combining asthma-related hospitalizations, intubations and deaths. It also records serious adverse event counts for each group. These details characterize the study’s question and some of its safety reporting.
What the record does not provide is the numerical primary endpoint result, a treatment-effect estimate, a confidence interval or a test result. Without those, the size and precision of the intended comparison cannot be evaluated. The study’s stated aim to assess whether risk was the same does not show that the groups had equal risk, and the available serious adverse event counts do not answer the endpoint-specific question.
Nor does the record establish that a treatment caused or prevented an event. General statistical context: randomized comparisons can support causal interpretation when the design, follow-up, outcome ascertainment and analysis are adequate, but interpretation still depends on the actual results and their uncertainty. The registry record does not include enough primary outcome information to assess that evidence.
The terminated status is a registry fact, but the reason is not reported in the registry record. It should not be used to infer the trial’s findings, the reason for stopping, or whether the termination was related to safety. Likewise, the listed secondary outcomes identify measures of interest but do not indicate their observed results. The defensible interpretation is therefore limited: the record documents the planned comparison and selected safety figures, while leaving the central primary endpoint comparison unreported.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary safety outcome is a composite that includes serious but different event types: hospitalization, intubation and death related to asthma. Composite outcomes can make a safety question measurable as a combined endpoint, but interpretation depends on the event definitions, adjudication, frequency of each component and method of analysis. The registry record says events were adjudication-confirmed and that a patient could experience multiple events, making the distinction between participants and events particularly important.
The study also illustrates why an aim framed around whether risks are the same requires careful interpretation. General statistical context: failure to detect a difference is not evidence that risks are equivalent. Demonstrating equivalence or non-inferiority requires an appropriate design, a prespecified margin and estimates precise enough to address that margin. The registry record does not report these details or the primary numerical result, so the stated aim cannot be treated as a demonstrated conclusion.
Finally, the record includes serious adverse event counts that should not be confused with the defined primary endpoint. Keeping endpoint-specific results separate is essential when safety categories overlap but are not identical. Because numerical primary results, analysis details and missing-data procedures are not reported in the registry record, this trial is also a useful example of how registry design information can be clear while still leaving the central statistical comparison unresolved.
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 principal limitation for interpreting this trial from the registry record is that numerical results for the primary composite endpoint are not reported. There is no group-specific primary event count, treatment-effect estimate, confidence interval or p-value in the record. The stated safety question therefore cannot be answered quantitatively from the available registry information.
The endpoint description contains both a reference to first occurrences and a statement that the event count includes all adjudication-confirmed events, with multiple events possible for one patient. Without additional analysis details, it is difficult to determine how the primary analysis represented repeated events or how participant-level risk related to the reported event count. Component-specific results are also not reported in the registry record.
The registry lists enrollment but does not give primary endpoint denominators or participant flow. It does not report the trial’s sample-size justification, analysis model, missing-data approach, multiplicity procedure, interim analyses, or stopping rules. The status is terminated, but the reason is not reported in the registry record. These gaps prevent assessment of the planned versus analyzed population and the robustness of the intended comparisons.
The serious adverse event figures are available, but they are not the primary asthma-related composite outcome and should not be interpreted as a substitute for it. The registry also lists secondary outcomes without numerical results. As a result, the posted record supports description of the trial’s design and some safety reporting, but has limited value for estimating comparative effects or their precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Safety of Foradil in Patients With Persistent Asthma — NCT01845025.
- Registry record last updated 2017-03-21; status last verified 2017-01.
- Results first posted 2017-03-21.
- 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
NCT01845025 is a Phase 4 randomized, active-controlled, quadruple-masked, parallel-group study of formoterol plus fluticasone propionate versus fluticasone propionate with matching placebo in adolescents and adults with persistent asthma. The planned study period was 26 weeks. The registry records enrollment of 827, a start in 2013-05, primary completion in 2016-05, and terminated status.
The primary safety endpoint was a composite of asthma-related hospitalizations, intubations and deaths. The primary analysis population is described as randomized patients who took at least one dose. The registry record does not report numerical primary endpoint results, the reason for termination, or key statistical analysis details. It does report serious adverse event figures of 10 among 411 at risk for the combination group and 9 among 409 at risk for the fluticasone propionate group; these figures are separate from the primary endpoint.