Pragmatic Open - Label Randomized Clinical Trial of FF/UMEC/VI vs Non-ellipta Usual Care ICS-LABA for Adult Participants With Uncontrolled Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pragmatic Open - Label Randomized Clinical Trial of FF/UMEC/VI vs Non-ellipta Usual Care ICS-LABA for Adult Participants With Uncontrolled Asthma (NCT06372496), a randomized phase 4 study. The primary outcome is Change From Baseline (CFB) in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 24.

2. Clinical Question

The comparison is between treatment strategies in an open-label, active-controlled trial. The comparator is usual care rather than a single fixed ICS/LABA regimen: the record says treatment followed country-specific labels and allowed investigator discretion for a subset. That flexibility is relevant when interpreting the comparison, since the record does not identify one common control drug or dose.

The principal measurement is lung function, not a direct measure of symptoms or asthma control. The registry lists additional outcomes, including ACQ-7 improvement and other FEV1 thresholds, but the primary question concerns continuous change in trough FEV1 at Week 24. Results therefore describe the measured lung-function outcome and should not be treated as a complete account of every aspect of asthma control.

3. Trial Design

This is a phase 4 randomized, stratified, open-label, active-controlled, parallel-group effectiveness study. The registry identifies the allocation as randomized, masking as none, and the model as parallel. It describes the study as lasting 52 weeks, with the primary analysis at 24 weeks. The intervention descriptions likewise specify treatment for up to 24 weeks. The record does not explain the timing or purpose of any treatment or follow-up after that period.

The registry enrollment is 1358. The primary endpoint results use a modified Full Analysis Set, with 562 participants in the FF/UMEC/VI arm and 546 in the ICS/LABA arm. The secondary results described in the record use different denominators: 619 and 617 for each of the three binary outcomes with numerical results. Adverse-event counts use at-risk groups of 631 and 605. These different denominators reflect different reported analysis sets or outcome populations; the reasons for every difference are not reported in the registry record.

The intervention is a once-daily fixed-dose combination of FF, UMEC, and VI delivered by Ellipta. The control is non-Ellipta usual-care ICS/LABA according to country-specific regulatory labels, with high-dose ICS used for a subset at investigator discretion. This is an effectiveness comparison of the named strategy against usual care, not a comparison against one specified control product and dose.

The study is listed as active, not recruiting. The registry record gives a start date of 2024-04-16 and a primary completion date of 2025-07-28. The stratification factors, allocation concealment procedures, detailed visit schedule, and protocol-specified statistical plan 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: The results are presented on primary completion date and additional results will be provided within a year of study completion.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) - Modified 1 included all randomized participants who received at least 1 prescription of study intervention excluding participants from one site with evidence of falsified participants. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline (CFB) in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 24, measured over Baseline (Day 1) and at Week 24.

The primary endpoint is change from baseline in trough forced expiratory volume in one second (FEV1) at Week 24, measured in liters. FEV1 is the maximal amount of air a person can forcefully exhale in one second. The registry defines trough FEV1 on treatment as the last FEV1 value obtained before the morning dose of study intervention.

Baseline is the last acceptable or borderline acceptable pre-dose FEV1 at the randomization visit on Day 1. Change from baseline is calculated by subtracting that baseline value from the post-dose Week 24 value. A positive change therefore represents a higher measured FEV1 at Week 24 than at baseline, while a negative change represents a lower measured value. The endpoint uses a continuous measurement, so it retains more detail than a simple classification of participants as improved or not improved according to a threshold.

FEV1 is used as a measure of lung function, and the registry identifies it as the primary outcome for comparing the groups. It is not, by itself, a complete measure of symptoms, daily functioning, or every aspect of asthma control. The trial also lists ACQ-7 and threshold-based FEV1 outcomes as secondary measures. Those can add context, but the primary result answers the specific question about mean change in trough FEV1 at Week 24.

The sponsor’s posted primary analysis reports an ANCOVA estimate of the net mean difference between groups. The registry record does not specify the covariates included in that ANCOVA or provide the full model specification.

7. Results Posted in the Registry

• Inhaled Corticosteroid [ICS]/Long-acting Beta-2 Agonist [LABA]: mean 0.11 versus 0.18 on control; difference -0.07 (95% CI -0.12 to -0.01), standardized effect d = -0.15; z-test p = 0.015.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants Achieving Greater Than Equal to (>=) 0.5 Point Improvement (Decrease) From Baseline for the Asthma Control Questionnaire-7 (ACQ-7) at Week 24

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Inhaled Corticosteroid [ICS]/Long-acting Beta-2 Agonist [LABA]: 71.8% (443/617) versus 79.0% (489/619) on control; risk difference -7.2 percentage points (95% CI -12.0 to -2.4), risk ratio 0.91 (0.85–0.97); unadjusted two-proportion z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Inhaled Corticosteroid [ICS]/Long-acting Beta-2 Agonist [LABA] than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With Change From Baseline in Trough FEV1 >= 100 mL at Week 24

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Inhaled Corticosteroid [ICS]/Long-acting Beta-2 Agonist [LABA]: 29.5% (182/617) versus 46.0% (285/619) on control; risk difference -16.5 percentage points (95% CI -21.9 to -11.2), risk ratio 0.64 (0.55–0.74); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Inhaled Corticosteroid [ICS]/Long-acting Beta-2 Agonist [LABA] than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With Change From Baseline in Trough FEV1 >= 0 mL at Week 24

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Inhaled Corticosteroid [ICS]/Long-acting Beta-2 Agonist [LABA]: 51.5% (318/617) versus 65.9% (408/619) on control; risk difference -14.4 percentage points (95% CI -19.8 to -8.9), risk ratio 0.78 (0.71–0.86); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Inhaled Corticosteroid [ICS]/Long-acting Beta-2 Agonist [LABA] than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes with numerical results in the registry point in a direction consistent with the primary Week 24 result: the FF/UMEC/VI group had higher reported proportions meeting each of the three listed criteria than the ICS/LABA group. These outcomes cover improvement in ACQ-7 and two thresholds for change in trough FEV1. They provide related perspectives on asthma control and lung-function change, while measuring different constructs from the continuous primary endpoint.

The remaining secondary outcomes listed in the record include later measurements, additional FEV1 thresholds, and ACQ-7 improvement at Week 52. The record describes a 52-week study with the primary analysis at Week 24. Secondary findings at different times or using different cutoffs are not direct substitutes for the primary result, and results for every listed outcome are not included in the numerical details considered in this account.

Secondary analyses generally carry less evidential weight when many outcomes or comparisons are examined without a reported multiplicity adjustment. Testing multiple outcomes creates more opportunities for apparently notable findings to occur by chance. The registry record lists 38 posted secondary outcomes and 11 analyses, but the multiplicity strategy is not reported. This does not negate the reported secondary estimates; it means their p-values and confidence intervals should be interpreted with caution alongside the primary analysis.

The outcomes also have different denominators from the primary result. The registry does not fully explain those population differences or report enough detail to determine whether each secondary analysis followed a prespecified hierarchy. The overall pattern is therefore useful as context, but it does not establish that every secondary comparison is confirmatory or equally reliable.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants Achieving Greater Than Equal to (>=) 0.5 Point Improvement (Decrease) From Baseline for the Asthma Control Questionnaire-7 (ACQ-7) at Week 24
• Percentage of Participants Achieving the Composite Endpoint (Optimized) at Week 52
• Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 52
• Percentage of Participants With Change From Baseline in Trough FEV1 >= 100 mL at Week 24
• Percentage of Participants With Change From Baseline in Trough FEV1 >= 100 mL at Week 52
• Percentage of Participants With Change From Baseline in Trough FEV1 >= 0 mL at Week 24
• Percentage of Participants With Change From Baseline in Trough FEV1 >= 0 mL at Week 52
• Percentage of Participants Achieving >= 0.5 Point Improvement (Decrease) From Baseline for the ACQ-7 Score at Week 52

9. Statistical Interpretation

10. Statistical Methods Explained

The statistical methods answer different questions. The primary outcome is continuous: it records a change in FEV1 in liters. The sponsor reports an ANCOVA estimate of the net mean difference. Secondary threshold outcomes are binary: each participant either meets the specified criterion or does not. Their sponsor analyses include odds ratios. These effect measures are not interchangeable, because they summarize different features of the data.

What does the primary mean difference represent?

A mean difference compares average values between groups. For the primary outcome, the sponsor’s net estimate is 0.068 L, with a 95% confidence interval from 0.036 to 0.099. The positive direction corresponds to the FF/UMEC/VI group having the higher estimated average change, given the group ordering in the sponsor result. A mean difference does not say that every participant had a change of that size; individual outcomes can vary around the group average.

The sponsor used ANCOVA, a statistical approach that can estimate a group contrast while accounting for variables included in the model. The registry record does not report which covariates were included, how they were coded, or the complete model specification. It is therefore not possible to reconstruct the sponsor’s adjusted estimate from the record alone.

What does the unadjusted recalculation add?

The recalculated primary comparison uses the posted group means and standard errors, with an approximate pooled standard deviation noted in the calculation. It is an unadjusted comparison based on summary statistics, rather than a reproduction of the sponsor’s ANCOVA. Its contrast is ICS/LABA minus FF/UMEC/VI, so its negative sign expresses the same direction as the positive sponsor contrast when the order of subtraction is reversed. Its p-value is 0.015. Because the methods and contrast presentation differ, the recalculation is best read as a simple check on the posted summaries, not as the trial’s primary inferential result.

A p-value describes how incompatible the observed data are with a specified null model under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry provides p-values for the sponsor analyses and an unadjusted p-value for the recalculation, but the full model assumptions and diagnostics are not reported.

How do odds ratios describe the secondary outcomes?

For a binary outcome, an odds ratio compares the odds of meeting the outcome in one group with the odds in the other. The registry reports sponsor odds ratios of 1.47 for the ACQ-7 improvement threshold, 2.01 for an increase in trough FEV1 of at least 100 mL, and 1.77 for an increase of at least 0 mL. Their reported 95% confidence intervals are 1.13 to 1.92, 1.58 to 2.56, and 1.41 to 2.24, respectively. An odds ratio is not a percentage-point difference and should not be interpreted as one.

The posted group percentages offer a more direct description of how many participants met each threshold in each arm. The sponsor odds ratios summarize relative odds from a regression analysis. For the ACQ-7 result, the sponsor reports logistic regression and p = 0.004. For the two FEV1 threshold results, the record reports odds ratios and confidence intervals but does not provide a p-value or method for the sponsor analysis.

Why do denominators and populations matter?

The primary analysis reports 562 and 546 participants, whereas the three secondary results use 619 and 617. The adverse-event summaries use at-risk groups of 631 and 605. A denominator identifies the participants included for a particular result; it is not automatically the same as the full enrollment. Different denominators can arise from outcome-specific availability or analysis-set definitions, but the reasons for each difference are not reported in the registry record.

The primary population description identifies a modified Full Analysis Set, excludes participants from one site because of evidence of falsified participants, and says only participants measured and analyzed contributed data. The record does not provide enough detail to assess every consequence of these population choices. In general, an analysis restricted to participants with measured outcomes may be affected if missing measurements are related to outcomes or treatment group. The missing-data methods and sensitivity analyses are not reported.

General statistical interpretation also depends on the analysis plan, outcome definitions, and assumptions. The registry identifies ANCOVA and logistic regression for some sponsor analyses, but does not report full model details, diagnostics, prespecified handling of protocol deviations, or the complete multiplicity strategy. Those details are needed to assess how the reported estimates would behave under alternative analytic choices.

11. Confidence Intervals and Precision

A confidence interval gives a range of estimates compatible with the data and the statistical model at the stated confidence level. It communicates uncertainty around an estimate; it is not a range containing a specified proportion of individual participants’ outcomes, nor does it assign a probability to the true effect after the data have been observed.

For the primary ANCOVA result, the estimated net mean difference is 0.068 L and the 95% confidence interval extends from 0.036 to 0.099. The interval is entirely on the positive side of zero, consistent with the reported p < 0.001 for a test of no difference under the sponsor’s analysis. Its width also shows that the point estimate is not known exactly. The confidence limits concern the estimated group contrast, not the range of individual FEV1 changes.

The recalculated unadjusted comparison is based on group summary statistics and uses an approximate pooled standard deviation. Its estimate and p-value are useful for understanding the simple contrast but do not carry the same model-based adjustment as the sponsor ANCOVA. The recalculated confidence limits are not needed to interpret the sponsor’s reported interval.

For the secondary endpoints, the sponsor reports 95% confidence intervals for odds ratios. Each interval describes uncertainty in the corresponding odds ratio, not in a risk difference or percentage-point contrast. The registry does not report confidence intervals for the arm percentages themselves in these results. Precision also depends on the analysis population and outcome denominator, which differ from the primary analysis population. The registry record does not report a formal assessment of whether any interval is narrow enough to establish a clinically important difference.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for each power target, because the reported outcomes are not time-to-event outcomes. The registry’s planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects equal to 100%, 75%, or 50% of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the number of participants per arm estimated to be needed, under those planning assumptions, for an 80% chance of detecting the specified effect if that effect is the true one. The 90% power column gives the corresponding requirement for a 90% chance. These are planning probabilities tied to assumed effects and analysis conditions; they are not probabilities that the observed result is true.

Each planning row changes the effect size used for the illustration. Planning for a smaller fraction of the observed effect requires more participants per arm than planning for the full observed effect. This relationship is a general feature of statistical planning: smaller effects are harder to distinguish from random variation, so more observations are typically needed under otherwise similar assumptions. The displayed counts should be read as hypothetical planning requirements rather than as a reconstruction of the trial’s original recruitment target. This is not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.068; pooled standard deviation σ = 0.464.
2. n = 2 × (1.96 + 0.842)² × 0.464² / -0.068² = 730.3, rounded up to 731 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.068                      # observed difference in means
sigma <- 0.463805360825595                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(6372496)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 731 (80% power), 978 (90% power)
 75% of observed effect: n per arm = 1,299 (80% power), 1,739 (90% power)
 50% of observed effect: n per arm = 2,922 (80% power), 3,911 (90% power)
power.t.test: 731.2 
Simulated power at n = 731 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as ANCOVA, with a net mean difference of 0.068 L, a 95% confidence interval from 0.036 to 0.099, and p < 0.001. This is the trial’s reported primary analysis and should be distinguished from the unadjusted recalculation based on group summaries.

The recalculation reports a mean difference of -0.068 L and an unadjusted p-value of 0.015 because its contrast is ICS/LABA minus FF/UMEC/VI, rather than the sponsor’s FF/UMEC/VI minus ICS/LABA ordering. Reversing a subtraction reverses the sign. The calculation also uses a simple unadjusted approach and an approximate pooled standard deviation, while the sponsor used ANCOVA. Different methods can produce different inferential results even when the direction of the group contrast agrees.

The record does not give the full ANCOVA model specification, including its covariates, so the sponsor result cannot be independently reproduced from the posted group summaries alone. The recalculation is a transparent summary-statistic check, not a replacement or correction of the sponsor’s analysis. No discrepancy is flagged in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and numerous secondary outcomes, including binary thresholds, continuous FEV1 measures, and ACQ-7 outcomes at different times. It reports 38 posted secondary outcomes and 11 analyses. When several outcomes are tested, the chance of at least one seemingly notable result can increase if the testing strategy does not account for multiplicity. Statistical methods to address this include prespecified testing sequences or adjustments to inference, but the registry record does not report whether such a strategy was used.

The registry reports sponsor p-values for the primary endpoint and some secondary analyses, but that alone does not establish how outcomes were prioritized or whether secondary findings were adjusted. The ACQ-7 logistic regression result has a reported p-value; the sponsor’s posted odds ratios for the two FEV1 threshold outcomes do not include p-values in the record. The full statistical analysis plan and the status of each secondary outcome as confirmatory or exploratory are not reported in the registry record.

The primary population is described as a modified Full Analysis Set. It included randomized participants who received at least one prescription of study intervention, excluded participants from one site because of evidence of falsified participants, and included only participants who were measured and analyzed for the reported outcome. The primary arm counts are 562 and 546, while the secondary endpoint counts are 619 and 617 and the adverse-event at-risk counts are 631 and 605. The registry does not provide a complete explanation for all differences among these denominators.

Missing-data handling can affect estimates when participants without measurements differ systematically from those with measurements. General approaches include assumptions about the missing outcomes and sensitivity analyses that test alternative assumptions. The registry record does not report its missing-data methods, the amount or pattern of missing endpoint data, or sensitivity analyses for the primary result.

Other details needed for a full assessment are also not reported, including the covariates in the ANCOVA, the stratification factors, and the protocol’s approach to deviations from the assigned treatment. These gaps limit independent reconstruction and assessment of the complete analysis strategy; they do not by themselves establish that the reported analyses are biased.

16. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (0.3%), acute respiratory failure (0.2%), pneumonia (0.2%), cervix carcinoma (0.2%), large intestine polyp (0.2%).

The adverse-event summary reports serious adverse events in 10 of 631 participants at risk in the FF/UMEC/VI group and 7 of 605 in the ICS/LABA group. Other adverse events are reported for 18 of 631 and 4 of 605, respectively. The death counts are 0 and 1, respectively. These are registry counts for the stated at-risk groups and should not be read as adjusted comparisons.

Counts alone do not describe the timing, duration, severity distribution, or causal relationship of events to study treatment. The record lists serious adverse-event terms, including asthma, acute respiratory failure, pneumonia, cervix carcinoma, large intestine polyp, and acute pancreatitis, with percentages attached to those terms. The available information does not give enough detail to interpret the percentages by treatment group or to determine whether an event was considered treatment-related.

Safety comparisons require attention to the definitions used, follow-up time, population at risk, and possible differences in exposure. The registry record does not report a statistical comparison of these adverse-event counts or enough detail to establish causality. The counts therefore describe reported events but do not, on their own, quantify comparative safety or establish that a treatment caused an event.

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

The primary result is an estimated difference between randomized groups in mean change in trough FEV1 at Week 24. The sponsor’s ANCOVA estimate is 0.068 L, with a 95% confidence interval from 0.036 to 0.099 and p < 0.001. The interval indicates uncertainty around the estimated group contrast, while the p-value reflects the sponsor analysis’s test under its statistical model. The result concerns the average measured change, not the experience of every participant.

The secondary results provide additional outcome-specific information, including ACQ-7 improvement and threshold-based FEV1 changes. Their direction is consistent with the primary result among the outcomes with numerical results in the record. They do not establish that the same result applies to every secondary endpoint, time point, or participant. The record does not report a multiplicity strategy, and secondary findings should therefore be interpreted more cautiously than the primary analysis.

The trial is randomized but open-label. Participants and investigators were not masked according to the registry. Open-label status does not automatically invalidate a measured lung-function result, but it can matter for outcomes that involve participant reporting, investigator judgment, treatment decisions, or study conduct. The comparator was usual-care ICS/LABA based on country-specific labels, with investigator discretion for a subset, rather than a single fixed regimen.

These results do not establish the clinical importance of the estimated difference; the registry record does not report a threshold for clinical importance. They also do not provide a complete assessment of symptoms, daily functioning, treatment burden, or longer-term outcomes. The study is described as lasting 52 weeks, with the primary analysis at 24 weeks, and is listed as active, not recruiting. The reported Week 24 findings should not be taken as a conclusion about outcomes that are not reported or about all aspects of treatment choice.

18. Why This Trial Matters Statistically

This trial illustrates why the analysis method and the form of an outcome matter when reading clinical results. The primary endpoint is a continuous lung-function measure, and the sponsor reports an ANCOVA mean difference with a confidence interval. The simple recalculation from group summaries uses a different method and the reverse contrast order. Understanding that distinction prevents a sign change or a difference in p-values from being mistaken for a contradictory direction of effect.

It also shows why denominators must be read alongside estimates. The registry enrollment is 1358, but the primary endpoint, secondary outcomes, and adverse-event summaries use different group counts. Those populations answer related but not identical questions. Without a complete account of why each denominator differs, readers should avoid treating every result as if it came from the same set of participants.

The study’s comparator is pragmatic usual care, with country-specific labels and investigator discretion for a subset. That design addresses a different question from a tightly standardized comparison against one specified product and dose. The open-label design and the mix of continuous and threshold-based outcomes add further context for judging what each result can establish.

Finally, the registry reports many secondary outcomes but does not state a multiplicity plan, missing-data methods, or the full primary model specification. These omissions limit independent evaluation of the analysis strategy. The primary result remains interpretable as the sponsor’s reported Week 24 estimate, while its precision, population definition, and relation to secondary findings should be considered together.

19. 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 registry record does not report the covariates used in the primary ANCOVA, the stratification factors, or the complete statistical analysis plan. This limits independent reproduction of the sponsor’s adjusted estimate. The unadjusted recalculation provides a separate check based on summary statistics, but it cannot recover details that are absent from the record.

The description of the modified Full Analysis Set says that participants from one site were excluded because of evidence of falsified participants and that only participants measured and analyzed contributed data. The record does not provide a complete account of the exclusions, the reasons for missing measurements, or the consequences of these decisions for each endpoint. The primary results use different denominators from the secondary and safety summaries, and the reasons for all differences are not reported.

The open-label design means treatment assignment was not masked. This may be particularly relevant to participant-reported or judgment-based outcomes such as ACQ-7, though the registry does not provide evidence that the design altered any particular result. The usual-care comparator also permits variation according to country-specific labels and investigator discretion; the record does not provide details sufficient to characterize every control regimen or its use.

The registry lists many secondary outcomes and analyses, but does not report how multiplicity was handled or which secondary tests were confirmatory. Missing-data methods, sensitivity analyses, model diagnostics, and a threshold for clinical importance are also not reported. The study is described as 52 weeks long, while the primary analysis is at Week 24; the results concern the posted Week 24 findings and do not resolve later outcomes.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Pragmatic Open - Label Randomized Clinical Trial of FF/UMEC/VI vs Non-ellipta Usual Care ICS-LABA for Adult Participants With Uncontrolled Asthma — NCT06372496.
• Registry record last updated 2026-10-06; status last verified 2026-09.
• Results first posted 2026-10-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

The registry record describes a phase 4, randomized, stratified, open-label, parallel-group effectiveness study comparing once-daily FF/UMEC/VI with non-Ellipta usual-care ICS/LABA in adults with uncontrolled asthma. Enrollment is 1358. The study is described as lasting 52 weeks, with the primary analysis at Week 24, and is listed as active, not recruiting.

The primary endpoint is change from baseline in trough FEV1 at Week 24. The sponsor reports an ANCOVA net mean difference of 0.068 L (95% confidence interval 0.036 to 0.099; p < 0.001). The record also includes secondary outcomes and adverse-event counts, with different denominators across analyses.

The full statistical plan, missing-data methods, multiplicity strategy, and complete model details are not reported in the registry record. These limits matter when assessing the precision, reproducibility, and scope of the posted findings.