Spiolto® Respimat® (Tiotropium/Olodaterol) Versus Triple Combination Therapy in Everyday Clinical Treatment Practice for Chronic Obstructive Pulmonary Disease (EVELUT®): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Spiolto® Respimat® (Tiotropium/Olodaterol) Versus Triple Combination Therapy in Everyday Clinical Treatment Practice for Chronic Obstructive Pulmonary Disease (EVELUT®) (NCT03954132), a registered phase not stated study. The primary outcome is Change in Modified Medical Research Council (mMRC) Score Between Baseline and After End of Observation.

2. Clinical Question

This is a comparative question about patient-reported breathlessness after a treatment switch in routine clinical practice. It is not a randomized treatment comparison: physicians selected the switch, and the groups may differ in characteristics that influenced that choice. Propensity-score matching was used to define the primary-outcome population, but the matching details and the characteristics used to create comparable sets are not reported in the registry record.

The registry record lists 469 participants enrolled. That figure describes enrollment, not necessarily the number contributing to the primary endpoint. The primary-outcome population excludes patients who could not be matched, and the number with endpoint data is not reported in the registry record. No numerical group results, estimated between-group contrast, or confidence interval for the primary outcome are reported in the registry record.

3. Trial Design

EVELUT® is described as an open-label, comparative, multicentre cohort study in patients with COPD who were symptomatic despite maintenance LABA/ICS treatment. In routine clinical practice, the attending physician switched patients to either Spiolto® Respimat® or triple therapy. The registry record describes an observation period of approximately 12 weeks, with the primary endpoint scheduled from baseline at Visit 1 to Visit 2, planned at 12 weeks and allowed up to a maximum of 42 weeks.

The record lists 469 participants enrolled and identifies Boehringer Ingelheim as the sponsor. The study status is completed. The recorded start date is 2019-06-07, and the primary completion date is 2021-06-30. These administrative dates do not establish when individual participants were assessed or how long each person was followed.

The comparison is not described as randomized; allocation is not stated. Treatment choice was made by the attending physician, so the study reflects treatment decisions in routine care rather than assignment under a randomized protocol. A propensity-score matched set is specified for the primary outcome. Patients who could not be matched were excluded from that set, but matching variables, matching procedure, balance diagnostics, and the number retained are not reported in the registry record.

The primary outcome is change in mMRC score between baseline and the end of observation. Secondary outcomes listed include physician global evaluation at baseline and at the end of observation, patient satisfaction with inhaler and therapy at the end of observation, and responder counts based on changes in mMRC and CAT. The registry record lists seven outcome measures, while the available descriptions name only some of them. It reports no analyses, and numerical primary or secondary outcome results 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: All patients were screened for eligibility prior to participation in the trial. 6 patients were not recruited and treated. 24 patients in the treated set had at least one violations of the in- and/or exclusion criteria and were not included in the per protocol set (and the derived matched set).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Matched set (MS): All patients with informed consent who met all inclusion criteria as well as no exclusion criteria and have received at least one dose of Spiolto® Respimat® or triple combination (free or fixed LAMA + LABA+ ICS), excluding all patients who could not be matched in the propensity score matching, patients with missing data for this outcome measure were not replaced or imputed.

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: Treated set (TS): All patients with informed consent who have received at least one dose of Spiolto® Respimat® or triple combination (free or fixed LAMA + LABA+ ICS).

6. Primary Endpoint

The registry lists the primary outcome as Change in Modified Medical Research Council (mMRC) Score Between Baseline and After End of Observation, measured over Baseline at Visit 1 (day 0) and Visit 2 (planned at 12 week, up to a maximum of 42 weeks)..

The primary endpoint is change in the modified Medical Research Council (mMRC) dyspnea score between baseline and the end of observation. The mMRC is a patient-reported measure based on one question about when breathlessness occurs across everyday activities. Its scale runs from 0 to 4: 0 represents no disability from dyspnea and 4 represents the greatest severity on the scale. The registry defines the change as the Visit 1 score minus the Visit 2 score.

General: A symptom scale can make a subjective experience more consistently recordable over time, allowing a study to describe how reported symptoms vary from baseline. With this change convention, a positive value would indicate a lower score at Visit 2 than at baseline; a negative value would indicate a higher score at Visit 2. This describes the direction of the scale arithmetic, not a result from this study.

The registry identifies 1.0 point as the minimum clinically important difference (MCID). That threshold is a reference for interpreting the size of a change; it does not establish that participants in this study reached that change. The actual mean change, its 95% confidence interval, and any between-group estimate are not reported in the registry record. Consequently, the record does not allow readers to assess the observed change against the MCID or to judge its precision.

Visit 2 was planned at 12 weeks, with a maximum interval of 42 weeks. The timing range matters when interpreting a change because the measurement is tied to the actual observation interval. Individual follow-up timing and the distribution of assessment times are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome: change in mMRC score, summarized as a mean with a 95% confidence interval. The primary analysis itself is not reported in the registry record. In particular, the record does not state the statistical model, any covariate adjustment, the method used to account for matching, the standard-error calculation, or how participants with incomplete measurements were handled. The methods below explain general statistical concepts; they should not be read as a description of unreported procedures used in this study.

What does a mean change describe?

General: A mean change summarizes the average difference between a participant’s baseline and follow-up measurements, according to the change convention set by the study. It can be useful for describing the average symptom-score movement in a group. It does not show how changes varied among participants, whether most people moved in the same direction, or whether a small number of large changes influenced the average. The registry gives no group means or participant-level distribution of changes for this study.

The specified convention is baseline minus follow-up. Since lower mMRC scores represent less dyspnea on the described scale, the sign of a mean change must be read with that convention in mind. No observed mean is available in the registry record, so the direction of the study’s group changes cannot be stated.

What does a confidence interval contribute?

General: A confidence interval presents a range of values compatible with an estimate under the statistical method and its assumptions. It communicates precision in a way a point estimate alone cannot. A relatively broad interval indicates that the estimate is uncertain across a wider range of values; a narrow interval indicates greater precision, subject to the validity of the method. Intervals do not correct selection bias, confounding, measurement problems, or missing data.

The registry lists a 95% confidence interval for the primary measure, but does not report its limits. Nor does it report a between-group confidence interval. Thus, the specified interval type is known, but its numerical interpretation is not possible from the registry record.

Why does the cohort design matter?

General: In a randomized trial, random assignment is intended to make treatment groups comparable on average with respect to both measured and unmeasured characteristics. In an observational cohort, treatment choices can be related to patient features, clinician judgments, or other factors that may also relate to outcomes. A difference between groups can therefore reflect both treatment and group composition.

The registry describes physician-selected switching in routine practice and a propensity-score matched set. In general, propensity-score matching pairs or groups participants based on estimated treatment-selection probabilities derived from recorded characteristics. It can improve comparability on included measured characteristics when the method is appropriate and the data have adequate overlap. It cannot balance unmeasured factors by itself. The matching variables, algorithm, balance assessment, and matched-set size are not reported in the registry record, so the success and implications of matching cannot be evaluated.

What can be inferred from the analysis description?

The registry record reports zero analyses. It does not identify an analysis population beyond describing the matched set for the primary outcome, and it does not give the number with endpoint measurements. The record does not report whether the primary analysis compared within-group changes, compared changes between groups, or used a model that adjusted for baseline score or other variables. It also does not describe any handling of repeated observations or differences in follow-up timing. These choices can affect estimates and uncertainty, so they cannot be reconstructed from the endpoint definition alone.

The brief study description says participants were observed for approximately 12 weeks, while the endpoint timeframe allows Visit 2 up to a maximum of 42 weeks. General: If follow-up timing varies, the interpretation of a measured change depends partly on when the follow-up measurement was taken. A statistical analysis may address that variation in different ways, but the registry record does not state whether or how timing was incorporated.

How should planning illustrations be read?

General: A sample-size calculation based on an observed effect is a planning illustration. It describes the participant count associated with specified assumptions, such as a target power, significance level, allocation, and assumed effect size. It is not an observed study result and should not be confused with post hoc or observed power. A planning calculation also does not demonstrate that the study was designed around that effect.

The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is total events using Schoenfeld; for other outcomes, it is participants per arm. These are assumptions for a planning illustration, not evidence of the study’s original design or its achieved precision. The trial’s own sample-size justification is not reported in the registry record, and the record contains no analysis results from which to assess a study-specific observed effect.

The posted registry information therefore supports an explanation of the endpoint and the broad design, but not a reconstruction of the primary analysis. Without the estimate, confidence interval, analysis sample, and analysis method, the magnitude, precision, and robustness of the outcome cannot be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry names several secondary outcomes in addition to the primary mMRC change. These include physician global evaluation at baseline and at the end of observation, patient satisfaction with inhaler and therapy at the end of observation, and responder counts based on changes in mMRC and CAT. The record lists seven outcome measures, but the available descriptions do not name all seven. Numerical results for the listed outcomes are not reported in the registry record.

Multiplicity concerns arise when a study evaluates several outcomes or several comparisons: the more statistical tests undertaken, the greater the opportunity for a nominally unusual result to occur by chance. General: Methods such as hierarchical testing or adjusted significance thresholds can address this issue, but the registry record does not report whether any multiplicity procedure was planned or used. It also does not state which secondary outcomes, if any, were designated for formal hypothesis testing. No conclusions about multiplicity control can be drawn.

The record does not report missing-data counts, reasons for missingness, imputation methods, or sensitivity analyses. It also does not state how many participants had both baseline and follow-up mMRC scores. The total enrollment of 469 should not be assumed to be the endpoint analysis size, particularly because the primary population is described as a matched set that excludes unmatched patients.

The registry identifies the matched set as the primary-outcome population, but does not report a complete analysis-population definition or the number analyzed. The number of analyses is listed as zero. Whether the analysis followed an intention-to-treat, per-protocol, complete-case, or other approach is not reported in the registry record. These omissions limit assessment of selection, missing-data handling, and the potential impact of multiple outcome testing.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: hypertension (0.3%).

The registry reports serious adverse event figures separately for the two treatment groups. In the Spiolto® Respimat® group, 329 participants were listed at risk and 1 was listed with a serious adverse event; no deaths were listed. In the triple-therapy group, 134 participants were listed at risk, with 0 listed with a serious adverse event and 0 deaths.

The registry also lists hypertension at 0.3% among the top serious terms. The record does not specify in that entry which treatment group the term belongs to or provide further detail about the event. No other serious terms are listed in the available information.

General: “At risk” is the group size used for the adverse-event listing; it should not automatically be treated as the number with complete follow-up for every safety outcome. Counts of participants with events do not describe event severity beyond the serious-event classification, timing, duration, recurrence, or causal relationship to treatment. The record does not report those details.

These figures describe the events recorded in the registry and should not be interpreted as a comparative safety estimate. The groups were not described as randomized, their sizes differ, and the registry record gives no statistical comparison of serious adverse events. The counts alone cannot establish whether a difference is due to treatment, chance, or differences between the groups.

12. What the Result Does, and Does Not, Mean

The registry record establishes that EVELUT® was a completed, open-label comparative cohort study in symptomatic patients with COPD who switched from LABA/ICS maintenance therapy to either Spiolto® Respimat® or triple therapy in routine practice. It identifies change in mMRC score as the primary endpoint and describes the endpoint scale, timing, and sign convention. It also specifies the MCID as 1.0 point.

It does not report the numerical primary outcome, a between-group estimate, confidence intervals, or statistical test results. Therefore, the record cannot establish how mMRC scores changed, how precise any change estimate was, or whether the groups differed. The MCID is a reference for interpreting a change, not evidence that the threshold was reached in this study.

The record also does not report numerical results for the named secondary outcomes. Although it lists 469 participants enrolled, the primary outcome uses a matched set that excludes patients who could not be matched. The number included in the matched set and the number with available endpoint measurements are not reported. Consequently, enrollment cannot be used as a substitute for the analysis population.

General: A nonrandomized comparison can describe outcomes among patients receiving different treatments in practice, but observed group differences may reflect treatment selection and other differences between groups. Propensity-score matching can address measured factors included in the matching process; it cannot establish that unmeasured factors are balanced. The registry record does not give enough matching detail to judge that process.

The serious adverse event counts are descriptive registry entries, not evidence of a causal effect or a complete safety comparison. Taken together, the available record describes the study question and some design features, but it does not provide the outcome estimates needed to assess the size, direction, or precision of treatment-group differences.

13. Why This Trial Matters Statistically

This study addresses a statistical challenge common in routine-care comparisons: treatment is selected by clinicians rather than assigned randomly. The treatments in EVELUT® were prescribed by attending physicians, and the registry record does not state that allocation was randomized. That design can reflect everyday practice, but it also means differences between groups may be related to patient or clinical characteristics that influenced treatment selection.

The registry’s matched-set definition makes the analysis population especially important. It excludes patients who could not be matched using the propensity score, so the comparison pertains to the matched population rather than automatically to everyone enrolled. Because the number matched, matching variables, and balance diagnostics are not reported, readers cannot determine how the matching changed the study population or how well measured characteristics were balanced.

The primary endpoint is a patient-reported symptom measure with a defined scale and an identified MCID. This makes the endpoint interpretable in principle: the scale gives a consistent way to describe breathlessness, and the MCID supplies a reference for evaluating the size of a change. But interpretation depends on the actual estimate and its uncertainty, neither of which is reported in the registry record.

The distinction between a clearly described endpoint and an available result is important. A registry can specify what investigators intended to measure without reporting the outcome values needed to assess the comparison. The record lists no analyses and does not give numerical primary or secondary findings. As a result, it supports examination of the design and reporting gaps, but not a statistical conclusion about the relative outcomes of the treatment groups.

The adverse-event counts also illustrate why descriptive data need context. Event counts are reported, but the record does not provide a formal comparison, detailed event information, or evidence that the groups were exchangeable. Statistical interpretation therefore depends not only on counts but also on study design, analysis populations, uncertainty, and completeness of reporting.

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 interpreting this trial from the registry record is the absence of numerical efficacy results. Although the primary endpoint, scale, timeframe, and confidence-interval type are described, the mean change, confidence-interval limits, and between-group estimate are not reported. The record lists no analyses, so the primary statistical comparison cannot be reviewed.

The cohort design is nonrandomized, with treatment switching determined by the attending physician in routine practice. Allocation is not stated. Differences in patient characteristics or clinical decision-making could affect both treatment selection and symptom outcomes. The record describes propensity-score matching, but does not report the matching variables, method, matched sample size, or balance diagnostics. The extent to which measured characteristics were balanced is therefore not assessable, and matching cannot address unmeasured factors on its own.

The enrollment figure of 469 does not show how many participants were included in the primary analysis. The primary population excludes patients who could not be matched, and the number with complete baseline and follow-up scores is not reported. Missing-data counts, reasons for missingness, and handling methods are also not reported in the registry record. The endpoint timeframe permits Visit 2 up to a maximum of 42 weeks, but the distribution of actual follow-up times is not reported.

Multiplicity procedures, the primary analysis model, covariate adjustment, and sensitivity analyses are not reported. The registry lists seven outcome measures but gives descriptions for only some of them. These gaps prevent evaluation of the statistical approach, the completeness of outcome reporting, and the robustness of any estimate. Safety information is limited to the listed serious-event counts and top term; details and a comparative safety analysis are not reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Spiolto® Respimat® (Tiotropium/Olodaterol) Versus Triple Combination Therapy in Everyday Clinical Treatment Practice for Chronic Obstructive Pulmonary Disease (EVELUT®) — NCT03954132.
• Registry record last updated 2024-04-24; status last verified 2024-04.
• Results first posted 2024-03-15.
• 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.

18. Record Summary

EVELUT® (NCT03954132) is a completed, open-label comparative cohort study sponsored by Boehringer Ingelheim. The registry lists 469 participants enrolled and describes symptomatic patients with COPD switching from LABA/ICS maintenance therapy to Spiolto® Respimat® or triple therapy in routine practice.

The primary endpoint is change in mMRC score from baseline to the end of observation, defined as Visit 1 minus Visit 2. Visit 2 was planned at 12 weeks, up to a maximum of 42 weeks; the stated MCID is 1.0 point. A propensity-score matched set is specified, excluding patients who could not be matched.

The registry record does not report numerical primary or secondary outcome results, analysis methods, or the number analyzed. It lists serious adverse events in each group and no deaths. The available safety figures are descriptive and do not establish a comparative treatment effect.