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 Buparid/PARI SINUS Versus Budes® Nasal Spray in the Therapy of Chronic Rhinosinusitis (NCT01955980), a randomized phase 1, phase 2 study. The primary outcome is Change of Inflammation of the Nasal Mucosa and Paranasal Sinus.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01955980 |
| Phase | Phase 1, Phase 2 |
| Condition | Rhinosinusitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Pari Pharma GmbH |
| Results posted | Yes |
2. Clinical Question
The study asked whether Buparid/PARI SINUS could help avoid or postpone sinus surgery in adults with chronic rhinosinusitis, and aimed to create data that could help select a clinically relevant endpoint for assessing that potential. The primary outcome posted in the registry record was change in inflammation of the nasal mucosa and paranasal sinus from baseline to week 8, measured using the Lund-Mackay score based on magnetic resonance imaging.
Population
Adult patients with chronic rhinosinusitis. The registry record lists rhinosinusitis as the condition and reports total enrollment of 19 participants. More detailed eligibility criteria are not reported in the registry record.
Intervention
Buparid; Treatment A: Buparid 1mg budesonide/2 ml nebulizer solution.
Comparator
Budes; Treatment B: Budes Nasal Spray 50 µg budesonide/pump.
Primary question
What change in the MRI-based Lund-Mackay inflammation score was observed from baseline to week 8 in each treatment arm? The posted primary outcome summarizes each arm; a direct between-arm estimate is not reported in the registry record.
The study was described as a pilot. Its stated purpose was to generate information for selecting an endpoint, rather than to establish a definitive answer about postponing surgery. Although avoiding or postponing surgery motivated the study, the primary outcome is an imaging score, not time to surgery or the proportion of participants who underwent surgery. The registry record does not report a result for surgery avoidance or postponement.
3. Trial Design
The registry record describes a randomized, parallel-group study with no masking. It is listed as Phase 1 and Phase 2 and as completed. Enrollment was 19: 10 participants in Buparid; Treatment A and 9 in Budes; Treatment B. The listed start date is 2015-10-27, and the primary completion date is 2018-09-27.
Treatment A was Buparid 1mg budesonide/2 ml nebulizer solution. Treatment B was Budes Nasal Spray 50 µg budesonide/pump. Both intervention entries are identified as budesonide. The registry record labels the allocation randomized, but the method used to generate or conceal the allocation sequence is not reported in the registry record. The allocation ratio is also not reported in the registry record.
The study was unmasked, so participants and study personnel were not described as blinded. Whether outcome assessors were masked is not reported in the registry record. This is relevant because the primary outcome involved image assessment, although the record states that two independent raters assessed the same images and that their scores were combined as an intraindividual mean score.
The primary endpoint was change in the Lund-Mackay score from baseline to week 8. The registry record also lists secondary outcomes concerning health-specific quality of life, nasal obstruction, inflammation of the nasal mucosa and paranasal sinus, and safety assessment. The total number of posted outcome measures is 5. The record does not describe visit schedules beyond the primary endpoint timeframe, treatment adherence, concomitant treatment, or follow-up beyond the stated outcome period.
The study’s brief summary says it should create data for selecting a clinically relevant endpoint to assess the potential of Buparid/PARI SINUS to postpone sinus surgery. That objective should be distinguished from the measured primary endpoint: the registry’s primary result is an imaging-score change, not a surgery outcome. The registry record does not report a separate outcome result for avoiding or postponing surgery.
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 | Buparid; Treatment A | Budes; Treatment B |
|---|---|---|
| STARTED | 10 | 9 |
| COMPLETED | 10 | 9 |
| NOT COMPLETED | 0 | 0 |
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 | Buparid; Treatment A | Budes; Treatment B | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 9 | 19 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 | 9 | 19 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 5 | 5 | 10 |
| Sex: Female, Male: Male | Participants | 5 | 4 | 9 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Germany | Participants | 10 | 9 | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Change of Inflammation of the Nasal Mucosa and Paranasal Sinus, measured over Change from Baseline to week 8.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change from baseline to week 8 in inflammation of the nasal mucosa and paranasal sinus. Inflammation was assessed using the Lund-Mackay score based on magnetic resonance imaging. The scale ranges from 0 to 24 points, with higher values indicating more severe mucosal thickness or opacification. The outcome was defined as the intraindividual mean score from two independent raters assessing the same images.
Using a defined imaging score gives the study a structured way to describe radiological changes over the specified period. The score is an intermediate measure of inflammation, rather than a direct measure of symptoms, quality of life, or whether surgery was avoided or delayed. The registry record lists health-specific quality of life and nasal obstruction among secondary outcomes, but those are distinct from the primary imaging endpoint.
Change scores describe the direction of movement relative to baseline: a negative change corresponds to a lower score at follow-up, while a positive change corresponds to a higher score. Since higher Lund-Mackay scores indicate more severe findings, the direction is clinically interpretable as a change in imaging severity. That interpretation does not by itself establish why a score changed, whether the change is meaningful to patients, or whether it affects the need for surgery.
The choice of endpoint was especially pertinent to this pilot’s stated aim of generating information for endpoint selection. However, the registry record does not report a threshold for a clinically meaningful change, nor does it report how the imaging result relates to later surgery decisions.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results summarize change separately for each arm. For Buparid; Treatment A, the median change was 0.0, with a 95% confidence interval from -2.0 to 5.5, among 10 participants. For Budes; Treatment B, the median change was -0.8, with a 95% confidence interval from -5.5 to 4.5, among 9 participants. The intervals in both arms have negative lower bounds and positive upper bounds, so the posted results are compatible with changes in either direction.
These are arm-level summaries, not a direct estimate of the difference between treatments. The registry record does not report a between-arm effect estimate, a confidence interval for that contrast, or a p-value. Therefore, the posted numbers do not provide a formal statistical comparison showing whether the groups differed. A reader should not infer a treatment advantage from comparing the two medians alone.
The confidence intervals indicate considerable uncertainty about each arm’s median change. They do not describe the range of individual participants’ changes, and they should not be read as certainty that the true median lies within the displayed endpoints. In general, a confidence interval describes uncertainty in an estimate under the assumptions of the analysis. Here, the registry record does not describe the method used to construct these intervals, so their exact statistical properties cannot be assessed from the posted entry.
The direction and size of an imaging-score change are not the same as evidence about avoiding or postponing surgery. The primary outcome was the MRI-based Lund-Mackay score from baseline to week 8. Surgery avoidance or postponement was the study’s stated motivation, but a surgery result is not reported in the registry record. Nor does the record establish a threshold at which an imaging-score change would count as clinically important.
The study enrolled 19 participants in total. In a pilot study of this size, estimates can be imprecise, and results may be sensitive to the experience of a small number of participants. The confidence intervals make that uncertainty visible, but the registry entry does not report a prespecified hypothesis test or a statistical plan that would clarify how the results were intended to be judged.
The registry lists the study as randomized, which is a design feature intended in general to support a fair comparison by balancing prognostic factors on average. Randomization does not guarantee balance in a small sample, and the record does not report baseline characteristics with which to assess balance. The unmasked design also means that expectations could potentially affect subjective outcomes or care decisions; whether this affected the image assessment cannot be determined from the registry record.
Overall, the posted endpoint results are descriptive summaries with broad uncertainty and no reported direct comparison. They can inform discussion of the observed imaging-score changes and the feasibility of measuring this endpoint in the study, but they do not establish a comparative effect or answer the surgery question.
9. Statistical Methods Explained
The primary results use medians to summarize change in the Lund-Mackay score within each treatment arm. A median is the middle observation when values are ordered. It can be useful when a measure may be skewed or when a small number of values could pull an arithmetic average. In this record, the median is reported for each arm, rather than as a single pooled summary.
The registry also reports a 95% confidence interval for each arm’s median change. In general, a confidence interval expresses uncertainty around an estimate: a narrower interval indicates greater precision than a wider interval, assuming comparable methods and data. A 95% confidence interval is not a statement that 95% of individual participants’ changes fall inside the interval. It is an interval for an estimated quantity, not a description of the spread of participants’ outcomes.
For Buparid; Treatment A, the median change is 0.0, with a 95% confidence interval from -2.0 to 5.5. For Budes; Treatment B, the median change is -0.8, with a 95% confidence interval from -5.5 to 4.5. The registry record does not report a separate measure of dispersion such as a standard deviation or interquartile range. It also does not describe the procedure used to calculate the confidence intervals. Those details matter when assessing how well the reported intervals match the data and the intended estimand.
What does an arm-level estimate show?
An arm-level median describes the observed change within one assigned group. It does not by itself quantify the effect of choosing one treatment rather than the other. To make a comparative claim, analysis would typically report a contrast between groups and its uncertainty, with an account of the statistical method used. A direct between-arm estimate and its uncertainty are not reported in the registry record. The two arm medians should therefore not be treated as though their difference were a posted comparative result.
Nor should one interpret the confidence intervals as a test of whether the treatments differ. A formal comparison needs an appropriate estimate of the contrast and its uncertainty, or a prespecified test with its result. The registry record reports neither a comparative p-value nor a comparative confidence interval. General statistical interpretation can explain what those quantities would convey, but it cannot replace missing results.
Why does the score’s direction matter?
The Lund-Mackay score ranges from 0 to 24 points, and higher values indicate more severe mucosal thickness or opacification. A change score compares a follow-up score with baseline. A negative value therefore represents a lower score at follow-up, while a positive value represents a higher score. This description concerns the imaging measure only. It does not establish that a change is noticeable to patients or that it changes decisions about surgery.
The endpoint is an intraindividual mean score from two independent raters who assessed the same images. Averaging raters’ scores can summarize assessments while reducing dependence on any single rating. The record does not report rater agreement, whether raters were masked to treatment or timepoint, or how disagreements were handled. It also does not report whether the same image-reading process was applied to every participant.
What can randomization and masking contribute?
In general, random assignment aims to reduce systematic differences between groups at the time of allocation. It does not ensure that a small study will have closely balanced groups, and it does not remove uncertainty in the outcome estimates. The registry identifies this study as randomized but does not report sequence generation, allocation concealment, or baseline comparability in the material.
The design is listed as having no masking. In general, lack of masking may influence expectations, reporting, behavior, or clinical decisions. An imaging outcome may seem more objective than a symptom rating, but image interpretation still involves human assessment. The record names two independent raters, but does not say whether they were blinded. The potential for measurement or performance bias therefore cannot be evaluated fully from this entry.
How should planning illustrations be read?
The sample-size section is a planning illustration based on the observed effect, not a report of the trial’s design justification or an estimate of observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such calculations show the sample size that a hypothetical future study might require under those assumptions. They do not show the probability that this completed study detected an effect, and they do not establish that the assumptions are suitable for a future trial.
The registry record does not report the trial’s sample-size justification, the method used to select its enrollment target, or a statistical analysis plan. The actual allocation was 10 participants in Buparid; Treatment A and 9 in Budes; Treatment B, rather than the equal allocation assumed for the planning illustration. The illustration and the observed study should be kept conceptually separate.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists four secondary outcome areas: health-specific quality of life, nasal obstruction, inflammation of the nasal mucosa and paranasal sinus, and safety assessment. It reports five outcome measures in total, including the primary outcome. The presence of several outcomes raises a general multiplicity issue: when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase. A study may address this with a prespecified hierarchy, adjustment, or a clearly exploratory interpretation.
Whether the investigators prespecified a hierarchy among outcomes, adjusted for multiple testing, or treated the secondary outcomes as exploratory is not reported in the registry record. No secondary outcome results are included in the registry record, and no analysis results are listed. The record therefore does not permit an assessment of multiplicity handling or a comparison of the primary and secondary findings.
The handling of missing outcome data is not reported in the registry record. The entry does not say whether all randomized participants contributed primary endpoint data, how missing images or assessments were treated, or whether any imputation or sensitivity analysis was used. The primary outcome population is not specified in the registry record. The analysis populations, such as whether the analyses followed randomized assignment or included only participants with available data, are also not reported in the registry record.
These omissions matter because missingness can affect both the estimate and its uncertainty, especially in a small study. Without the number assessed at each timepoint and the missing-data procedures, the reader cannot determine whether the posted arm summaries represent all enrolled participants or a subset with usable outcome data. The registry entry also does not report interim analyses, a stopping rule, or the statistical analysis plan. Those aspects should be treated as unreported rather than inferred from the results display.
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 |
|---|---|---|---|
| Buparid; Treatment A | 1 | 10 | 10.0% |
| Budes; Treatment B | 0 | 9 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Buparid; Treatment A | 0 of 10 |
| Budes; Treatment B | 0 of 9 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Buparid; Treatment A | 5 of 10 |
| Budes; Treatment B | 6 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Buparid; Treatment A | Budes; Treatment B |
|---|---|---|---|
| Aneurysm | Vascular disorders | 1 of 10 | 0 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Buparid; Treatment A | Budes; Treatment B |
|---|---|---|---|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 0 of 10 | 2 of 9 |
| Rhinitis | Infections and infestations | 1 of 10 | 1 of 9 |
| Sinusitis | Infections and infestations | 1 of 10 | 1 of 9 |
| Influenza | Infections and infestations | 1 of 10 | 1 of 9 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 10 | 0 of 9 |
| Nasal Dryness | Respiratory, thoracic and mediastinal disorders | 0 of 10 | 1 of 9 |
| Headache | Nervous system disorders | 0 of 10 | 1 of 9 |
| Depression | Psychiatric disorders | 1 of 10 | 0 of 9 |
| Tonsillitis | Infections and infestations | 1 of 10 | 0 of 9 |
Serious events with the highest arm-level rate: aneurysm (10.0%).
The registry lists serious adverse events for each arm. In Buparid; Treatment A, 1 of 10 participants is recorded as having a serious adverse event; in Budes; Treatment B, 0 of 9 participants are recorded as having one. No deaths are recorded in either arm. These are counts in a small study, not precise estimates of how often serious events would occur in a broader population.
The registry also lists Aneurysm at 10.0% among the top serious-event terms. This is a posted term and percentage, not a comparative estimate between the treatments. The record does not provide enough detail in the summarized entry to interpret the circumstances, timing, relatedness, or clinical course of that event.
In general, adverse-event counts depend on how events were defined, collected, and followed. The registry record does not report the event-collection procedures, attribution to treatment, exposure duration, or the criteria used to classify events as serious. The counts should therefore be read as registry-recorded observations, not as proof that an event was caused by a treatment or that no unlisted events occurred.
Other adverse events are also tabulated in the record, but the serious-event figures should not be conflated with those broader counts. With these enrollment numbers, one event changes the descriptive count substantially. The display is useful for seeing what was recorded in each arm, but it is not sufficient for a reliable comparison of safety profiles.
12. What the Result Does, and Does Not, Mean
The primary result describes MRI-based change in inflammation scores over the period from baseline to week 8. The Buparid; Treatment A median change was 0.0, with a 95% confidence interval from -2.0 to 5.5. The Budes; Treatment B median change was -0.8, with a 95% confidence interval from -5.5 to 4.5. Both intervals extend in negative and positive directions, and the registry record does not report a direct comparison between the arms.
These summaries do not establish that one treatment produced a greater change than the other. They also do not demonstrate that either treatment prevented or postponed surgery. Avoiding or postponing sinus surgery was part of the study’s stated objective, but the primary outcome was an imaging score and a surgery result is not reported in the registry record.
The score has an interpretable direction: higher values indicate more severe imaging findings, so a lower follow-up score corresponds to a negative change. However, the registry record does not state what magnitude of score change would be clinically important. An imaging change should not automatically be treated as an improvement in symptoms, quality of life, or surgical outcome. The record lists those other outcome areas, but does not include their results.
The study is identified as a pilot and enrolled 19 participants. Its results can be read as early descriptive information about the endpoint and the observed arm-level changes. They are not a definitive estimate of comparative treatment effect. The uncertainty intervals, lack of a reported between-arm analysis, and absence of details about missing data and analysis populations limit how far the findings can be interpreted.
In general, a randomized design can support causal comparison when the allocation process and analysis are appropriately implemented. Here, the record confirms randomization but does not report important procedural and analysis details. The trial’s unmasked status and the absence of information about assessor masking also leave uncertainty about potential sources of bias. These limitations do not erase the posted observations; they define the boundaries of what can be concluded from them.
The careful conclusion is therefore narrow: the registry reports arm-specific median changes and confidence intervals for the imaging endpoint, but does not report a formal treatment comparison or a result on surgery avoidance or postponement. Any broader claim would go beyond the posted evidence.
13. Why This Trial Matters Statistically
This trial matters statistically because it uses a pilot study to explore an endpoint for a clinical question that is ultimately about postponing or avoiding surgery. Its stated aim was to generate data for selecting a clinically relevant endpoint. The primary outcome, an MRI-based Lund-Mackay score, is a measurable imaging endpoint, but it is not itself a surgery outcome. Distinguishing the clinical objective from the endpoint measured is central to interpreting the results.
The study also illustrates why estimates and uncertainty should be read together. Each arm has a reported median and 95% confidence interval, while the registry record does not report a direct between-arm estimate. The intervals span changes in both directions. Looking only at the two medians would obscure the uncertainty and could invite an unsupported comparison.
The small enrollment makes this especially important. With 10 participants in one arm and 9 in the other, the summaries are best treated as descriptive. The record’s confidence intervals show uncertainty around the arm-level medians, while the absence of a comparative analysis means the main treatment contrast cannot be quantified from the registry entry.
There is also a measurement lesson. The outcome was assessed from MRI images by two independent raters, with the reported score defined as their intraindividual mean. This makes the measurement process more explicit than a simple unstructured judgment, but information about rater masking and agreement is not reported. In general, the reproducibility of an imaging measure is relevant when considering it as an endpoint for future research.
Finally, this record demonstrates the value of separating posted results from unreported methods. Randomization and the parallel-group design are stated, but allocation procedures, missing-data handling, analysis populations, and the statistical plan are not reported in the registry record. Those gaps matter when assessing reliability and planning later studies. The trial can generate useful questions about endpoint selection without providing a definitive answer about treatment effects or surgery.
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.
Several limitations specific to this study constrain interpretation. The enrollment was 19 participants, split between 10 in Buparid; Treatment A and 9 in Budes; Treatment B. Estimates from small groups are uncertain, and the reported confidence intervals are broad. The registry record does not report a direct between-arm effect estimate or formal statistical comparison, so the main comparative question is not answered by the posted primary results.
The endpoint was a change in MRI-based Lund-Mackay score from baseline to week 8. It measures imaging findings, not surgery avoidance or postponement. Although postponing surgery was part of the study’s stated objective, a surgery-related outcome result is not reported in the registry record. The record also does not report a clinically meaningful change threshold or evidence linking score changes to later surgery decisions.
The study was unmasked. The registry identifies two independent image raters but does not report whether they were masked to treatment or timepoint, or how agreement between raters was assessed. The allocation sequence generation and concealment procedures are not reported in the registry record. These gaps make it difficult to assess potential sources of bias beyond the design labels.
Important analysis details are also absent. Missing-data procedures, analysis populations, a statistical analysis plan, multiplicity handling, and sample-size justification are not reported in the registry record. The primary outcome population is not specified. Without these details, readers cannot determine the completeness of endpoint data or fully evaluate how the reported summaries were produced.
The record lists secondary outcome areas but does not include their results in the material. It likewise does not provide detailed adverse-event methods or context for the serious-event term. These limitations do not negate the posted values; they restrict them to a descriptive account of the registry results and leave key clinical and statistical questions unresolved.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Buparid/PARI SINUS Versus Budes® Nasal Spray in the Therapy of Chronic Rhinosinusitis — NCT01955980.
- Registry record last updated 2022-04-12; status last verified 2022-02.
- Results first posted 2022-04-12.
- 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
NCT01955980 is a completed randomized, open-label, parallel-group Phase 1 and Phase 2 pilot study of Buparid/PARI SINUS versus Budes Nasal Spray in adults with chronic rhinosinusitis. Total enrollment was 19: 10 participants in Buparid; Treatment A and 9 in Budes; Treatment B. The listed primary endpoint was change in MRI-based Lund-Mackay inflammation score from baseline to week 8.
The posted arm-level median changes were 0.0 for Buparid; Treatment A and -0.8 for Budes; Treatment B, each with a 95% confidence interval reported in the results display. The registry record does not report a direct between-arm analysis or a result for avoiding or postponing surgery. It lists secondary outcome areas in quality of life, nasal obstruction, inflammation, and safety. Details of missing-data handling, analysis populations, and the statistical plan are not reported in the registry record.