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 Trial of Roflumilast in Asthma Management (TRIM) (NCT03532490), a randomized phase 2 study. The primary outcome is Change in Asthma Control Test Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03532490 |
| Phase | Phase 2 |
| Condition | Asthma, Obesity |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 38 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Johns Hopkins University |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns adults with obesity and poorly controlled asthma. The registry lists asthma and obesity as conditions and describes the study as a pilot in obese adults with asthma. Further eligibility criteria and the operational definition of poorly controlled asthma are not reported in the registry record.
Intervention
Participants assigned to roflumilast received a 500 mcg oral tablet every other day during the first two weeks; if the participant tolerated the drug, the schedule changed to once daily. The registry does not report additional details about adherence or how tolerability was assessed.
Comparator
The control group received placebo tablets on the same every-other-day schedule during the first two weeks, followed by once-daily dosing if tolerated. The study is described as placebo-controlled, randomized, quadruple-masked, and parallel.
Primary question
The primary outcome asks how the change in Asthma Control Test score from baseline to 24 weeks compared between the roflumilast and placebo groups. The registry describes this as an unadjusted comparison. The posted group summaries are medians with interquartile ranges, but a test result or confidence interval for the between-group comparison is not reported in the registry record.
3. Trial Design
TRIM is a randomized, phase 2, parallel-group, placebo-controlled pilot trial. The registry describes masking as quadruple. It does not specify which participant or study roles were masked, so that detail is not reported in the registry record. The study enrolled 38 participants and is marked completed. Its recorded start date is 2018-08-03, and its primary completion date is 2021-07-30.
The comparison is between a roflumilast oral tablet and placebo. The roflumilast arm description specifies a 500 mcg dose every other day for the first two weeks, changing to once daily if tolerated. The placebo description gives the same schedule. Further information about treatment duration, adherence measurement, or what happened when a participant did not tolerate treatment is not reported in the registry record.
The primary outcome is change in Asthma Control Test score from baseline to 24 weeks. The registry presents results for 16 participants in the placebo group and 22 in the roflumilast group. The group-level change summaries are medians, and the recorded dispersion is an interquartile range. The registry describes the primary outcome comparison as unadjusted, but does not report the statistical test, a between-group estimate, or a confidence interval for that comparison.
Seven secondary outcomes are listed, covering weight, asthma symptoms, gastrointestinal symptoms, anxiety, asthma-related quality of life, general health status, and depressive symptoms. The registry reports no posted analyses. Details such as the allocation procedure, concealment, a formal analysis plan, and the sample-size justification are not reported in the registry record. The pilot designation describes the study's stated purpose; it does not by itself establish the precision of any particular estimate.
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 | Placebo Oral Tablet | Roflumilast 500 mcg Oral Tablet |
|---|---|---|
| STARTED | 16 | 22 |
| COMPLETED | 16 | 22 |
| 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 | Placebo Oral Tablet | Roflumilast 500 mcg Oral Tablet | Total |
|---|---|---|---|---|
| Participants analysed | 16 | 22 | 38 | |
| Age, Continuous | years | 56 (50 to 63) | 51 (43 to 59) | 53 (49 to 60) |
| Sex: Female, Male: Female | Participants | 14 | 19 | 33 |
| Sex: Female, Male: Male | Participants | 2 | 3 | 5 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 3 | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 14 | 19 | 33 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 | 10 | 16 |
| Race (NIH/OMB): White | Participants | 8 | 9 | 17 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 3 | 5 |
| Region of Enrollment: United States | Participants | 16 | 22 | 38 |
| Smoking status: Never | Participants | 14 | 18 | 32 |
| Smoking status: Former | Participants | 2 | 4 | 6 |
| Age at asthma onset (years) | years | 14 (9 to 37) | 21 (7 to 42) | 21 (7 to 42) |
| Asthma Control Test at Visit 2 (V2) | units on a scale | 19 (16 to 19) | 17 (14 to 18) | 17 (15 to 19) |
| Asthma Symptom Utility Index | units on a scale | .8 (.7 to .9) | .7 (.6 to .8) | .7 (.6 to .8) |
| Marks Asthma Quality of Life | units on a scale | 2.1 (1 to 4) | 1.8 (1.6 to 2.4) | 2 (1.5 to 2.5) |
| Patient Health Questionnaire-9 | units on a scale | 2 (1 to 4) | 2 (1 to 3) | 2 (1 to 4) |
| General Anxiety Disorder-7 | units on a scale | 0 (0 to 2) | 0 (0 to 1) | 0 (0 to 1) |
| Short form survey-36 | units on a scale | 59 (46 to 76) | 67 (52 to 78) | 62 (47 to 78) |
| Gastrointestinal Symptom Rating Scale | units on a scale | 1.4 (1.2 to 2.1) | 1.5 (1.1 to 1.9) | 1.4 (1.1 to 1.9) |
6. Primary Endpoint
The registry lists the primary outcome as Change in Asthma Control Test Score, measured over Baseline and 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | units on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in Asthma Control Test score between baseline and 24 weeks. The instrument is intended to help participants describe their asthma and its effects on how they feel and what they can do. Its questions ask about asthma symptoms and use of a rescue inhaler or nebulizer over the prior four weeks. Responses range from 1, indicating poorer control or more frequent symptoms, to 5, indicating better perceived control or no symptoms, for each question. The registry does not report the total-score range.
Change scores put the focus on how each participant's score differs between the baseline assessment and the later assessment. Comparing change between randomized groups is intended to describe whether the groups' score changes differ over that period. The registry specifies an unadjusted comparison, so it does not describe adjustment for baseline characteristics in this primary comparison.
The posted summaries are median changes, with an interquartile range for each group. A median describes the middle of the observed distribution, while the interquartile range describes the span of the central half of that distribution. These summaries can be useful when outcome changes are unevenly distributed or affected by unusually large or small values. They do not, on their own, quantify the uncertainty in the difference between the groups. A confidence interval or inferential test for that difference is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the primary endpoint, the posted median change is 2.0 units in the placebo group and 2.6 units in the roflumilast group. The reported interquartile ranges are 0.7 to 3.3 for placebo and 0.5 to 4.4 for roflumilast. The corresponding group sizes are 16 and 22. These are summaries within each randomized group, not an estimate of the treatment-group contrast. The registry does not report a numerical between-group estimate, confidence interval, or p-value for the primary comparison.
The medians therefore describe the center of each group's observed change distribution, while the interquartile ranges show how spread out the middle portion of each distribution was. The ranges overlap, but overlap between group summaries is not a formal test of a difference. Nor does a comparison of medians alone establish the direction, size, or statistical uncertainty of a between-group effect. Those conclusions require an appropriate comparison analysis and its uncertainty estimate, neither of which is posted in the registry record.
The primary outcome description calls for an unadjusted comparison of 24-week change. The exact test or model is not reported in the registry record. It is also not reported whether the posted group summaries include every randomized participant, only participants with an available 24-week assessment, or another analysis population. Missing outcome data and handling of those data are not reported. These omissions limit assessment of how the endpoint summaries relate to the original randomized groups.
The results should be read in the context of a pilot trial with 38 enrolled participants. The registry record does not give a sample-size justification, and it posts no analyses. This means that the numerical summaries can describe the observed participants, but the registry record does not supply the inferential results needed to judge the precision of a treatment-group contrast. Lack of a posted test or interval is not evidence that the groups were the same, and the group medians alone should not be used to assert that one treatment produced a reliable difference.
Secondary outcomes include change in weight, Asthma Symptom Utility Index, gastrointestinal symptoms, anxiety, asthma-related quality of life, general health status, and depressive symptoms. Although these outcomes are named, results or analysis estimates for them are not reported in the registry record. Their inclusion as planned or listed measures does not establish what was observed. Overall, the posted primary summaries describe change in each group; they do not provide a complete statistical account of the randomized comparison.
9. Statistical Methods Explained
The outcome summaries use the median and interquartile range. As a general statistical explanation, the median is the middle observation after values are ordered. It is less affected by extreme observations than the arithmetic mean. The interquartile range marks the interval from the lower to the upper quartile and describes the spread of the central half of observations. These summaries can be informative when a distribution is skewed or when a small number of values lie far from the center.
For this trial, the registry identifies the primary outcome parameter as a median and its dispersion as an interquartile range. It reports a median change of 2.0, with an interquartile range of 0.7 to 3.3, for placebo; the roflumilast median change is 2.6, with an interquartile range of 0.5 to 4.4. Those are group-level summaries. A difference between group medians is not automatically the same as the result of a formal analysis of individual-level changes. The precise method used for the primary comparison is not reported in the registry record.
What does an unadjusted comparison mean?
In general, an unadjusted comparison assesses the observed outcome contrast without including covariates such as baseline measurements or participant characteristics in a regression model. The registry says the primary comparison is unadjusted. It does not state whether the actual analysis compared change scores directly, used a rank-based test, or used another method. Nor does it report any adjustment or transformation details beyond describing the comparison as unadjusted. The analysis method should not be inferred from the choice of median summaries.
Why are confidence intervals useful?
In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method and its assumptions. It communicates uncertainty around an estimate, rather than only indicating which group summary is numerically larger. For a randomized comparison, an interval around the between-group effect can help readers assess both the range of plausible effect sizes and the precision of the estimate. The registry does not report a confidence interval for the primary between-group comparison. The group interquartile ranges are not confidence intervals: they describe variation among participants, not uncertainty around the treatment contrast.
What can group summaries establish?
As a general principle, a summary statistic compresses a distribution and necessarily leaves out individual-level detail. Two groups can have similar medians but different distributions, or different medians with substantial uncertainty around their contrast. A formal comparison depends on the underlying observations, the analysis method, and assumptions such as independence and the shape of the data distribution. Individual-level data and the exact analysis are not reported in the registry record, so those features cannot be assessed from the posted summaries alone.
How should the planning illustrations be read?
Any sample-size illustration associated with the observed effect is a planning exercise, not an estimate of the trial's observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is expressed as a fraction of the observed effect. In general, such an illustration asks what sample size could be needed under those assumptions to detect a specified effect. It does not show that the study was designed with those assumptions, that the effect is true, or that the trial had a particular probability of detecting it. The registry's own design justification is not reported. The trial enrolled 38 participants, but that number alone does not establish whether the study was adequately powered.
Why do analysis details matter?
Statistical results depend on what participants and observations enter an analysis, how missing measurements are handled, and which comparison is performed. The registry identifies 16 placebo participants and 22 roflumilast participants for the primary result, but does not explain the analysis population or missing-data approach. The exact inferential method and any prespecified analysis plan are not reported in the registry record. Those details are needed to evaluate whether the reported summaries and any treatment contrast answer the same question the trial set out to address.
The record posts no analyses. Consequently, no reported test statistic, p-value, or treatment-effect interval can be interpreted for the primary endpoint. Statistical concepts such as confidence intervals and model assumptions remain useful for understanding what information would strengthen an interpretation, but they do not substitute for results absent from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary Asthma Control Test change outcome and seven secondary outcomes. When a study evaluates multiple outcomes or performs multiple comparisons, the chance of finding at least one apparently unusual result by chance can increase. As a general statistical principle, multiplicity procedures may be used to control that risk, or a study may designate a single primary outcome and treat other findings as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any adjustment was planned.
The registry reports eight outcome measures and zero posted analyses. It therefore does not provide inferential results for the primary or secondary outcomes. No secondary outcome estimates are reported in the registry record, so the listed measures should not be read as evidence of observed changes.
Missing-data methods are also not reported in the registry record. The record does not state how many participants completed the 24-week assessment, whether missing scores occurred, or how any missing outcomes were handled. It does not identify whether the primary analysis used an intention-to-treat population, a per-protocol population, or another analysis set. The reported group sizes of 16 and 22 do not, by themselves, establish the rules used to select observations for the summaries.
In general, missingness can affect interpretation when the probability of having an observed outcome is related to participants' health, treatment, or outcome values. The impact depends on the amount and pattern of missing information and the assumptions used in analysis. With no missing-data description or analysis-population definition, those assumptions cannot be evaluated for this trial. These are reporting gaps; they do not establish that data were missing or that any particular method was used.
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 |
|---|---|---|---|
| Placebo Oral Tablet | 0 | 16 | 0.0% |
| Roflumilast 500 mcg Oral Tablet | 6 | 22 | 27.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo Oral Tablet | 0 of 16 |
| Roflumilast 500 mcg Oral Tablet | 0 of 22 |
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 |
|---|---|
| Placebo Oral Tablet | 10 of 16 |
| Roflumilast 500 mcg Oral Tablet | 22 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo Oral Tablet | Roflumilast 500 mcg Oral Tablet |
|---|---|---|---|
| Asthma exacerbation | Respiratory, thoracic and mediastinal disorders | 0 of 16 | 3 of 22 |
| Nausea | Gastrointestinal disorders | 0 of 16 | 2 of 22 |
| Loss of appetite | General disorders | 0 of 16 | 2 of 22 |
| Headache | General disorders | 0 of 16 | 1 of 22 |
| Dehydration | General disorders | 0 of 16 | 1 of 22 |
| Abdominal pain (umbilical hernia) | Gastrointestinal disorders | 0 of 16 | 1 of 22 |
| Hyperglycemia | Endocrine disorders | 0 of 16 | 1 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo Oral Tablet | Roflumilast 500 mcg Oral Tablet |
|---|---|---|---|
| Any emergent symptoms | General disorders | 4 of 16 | 13 of 22 |
| Headache | General disorders | 0 of 16 | 7 of 22 |
| Congestion, runny nose, sneezing | Respiratory, thoracic and mediastinal disorders | 2 of 16 | 5 of 22 |
| Acute upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | 0 of 16 | 3 of 22 |
| Diarrhea | Gastrointestinal disorders | 1 of 16 | 2 of 22 |
| Skin rash | General disorders | 1 of 16 | 2 of 22 |
| Muscle pain/aches | Musculoskeletal and connective tissue disorders | 1 of 16 | 2 of 22 |
| Chest discomfort | Cardiac disorders | 0 of 16 | 2 of 22 |
| chest pain | Cardiac disorders | 0 of 16 | 2 of 22 |
| Nausea | Gastrointestinal disorders | 0 of 16 | 2 of 22 |
Serious events with the highest arm-level rate: asthma exacerbation (13.6%), nausea (9.1%), loss of appetite (9.1%), headache (4.5%), dehydration (4.5%).
The registry reports serious adverse events in 0 of 16 participants in the placebo group and 6 of 22 participants in the roflumilast group. No deaths are reported in either group. It also reports other, non-serious adverse events affecting 10 of 16 placebo participants and 22 of 22 roflumilast participants. These counts describe participants affected, not the total number of separate event occurrences. The record does not provide further detail about event duration, severity grading for non-serious events, or the relationship of each event to treatment.
The listed serious-event terms include asthma exacerbation at 13.6%, nausea at 9.1%, loss of appetite at 9.1%, headache at 4.5%, dehydration at 4.5%, and abdominal pain (umbilical hernia) at 4.5%. These are registry-listed event percentages. The record does not report a comparative safety analysis, confidence intervals, or a causal assessment for these terms. The presence of an event during a trial does not by itself establish that study treatment caused it.
Safety counts from a small study are descriptive and may be imprecise. They should not be interpreted as a complete estimate of the frequency of harms in a broader population. The registry record does not report whether all adverse events were collected using the same procedures across groups or provide additional detail on exposure time. The figures describe what is posted, not a standalone determination of comparative safety.
12. What the Result Does, and Does Not, Mean
The posted primary results show median Asthma Control Test changes of 2.0 in the placebo group and 2.6 in the roflumilast group over the baseline-to-24-week timeframe. The interquartile ranges are 0.7 to 3.3 and 0.5 to 4.4, respectively. These figures describe the observed group summaries. They do not provide a formal estimate of the between-group effect or its uncertainty.
The trial is described as a pilot study of roflumilast for poorly controlled asthma in adults with obesity. Its randomized, placebo-controlled design provides a structure for comparing assigned groups, but the registry record does not report a statistical test, confidence interval, or p-value for the primary comparison. It also does not report the analysis population or how missing outcomes were handled. Therefore, the posted summaries alone cannot establish whether the groups differed beyond sampling variability or how precisely any difference was estimated.
The findings should not be extended beyond the measured endpoint, population, and follow-up described in the record. In particular, the Asthma Control Test is a participant-reported measure of asthma symptoms and their impact over the prior four weeks; it is not, by itself, a comprehensive measure of every aspect of asthma or general health. The other listed outcomes are not accompanied by results in the registry record.
The sample-size illustrations, if consulted, are planning calculations based on the observed effect under stated assumptions. They are not observed power and do not resolve uncertainty in the trial's estimated effect. The registry does not report its own sample-size justification. Similarly, adverse-event counts are descriptive and do not establish treatment causation or provide a definitive comparative safety assessment.
The appropriately limited reading is that the record reports group-level change summaries and safety counts for a completed pilot trial with 38 enrolled participants. It does not report the inferential analysis required to determine the precision or statistical evidence for a primary treatment-group contrast. Neither a claim of benefit nor a claim of no difference follows from the posted summaries alone.
13. Why This Trial Matters Statistically
This trial is statistically useful as an example of the distinction between descriptive results and comparative inference. The registry reports a median change and interquartile range for each arm, but does not report a between-group estimate or its uncertainty. Readers can describe the observed distributions, yet cannot use those group summaries alone to quantify how much the treatment groups differed or how precisely that contrast was estimated.
The setting also illustrates why the target population and endpoint matter. TRIM addresses poorly controlled asthma among adults with obesity, and its primary measure is a participant-reported asthma control score over the preceding four weeks. That measure captures an aspect of asthma experience, while the other listed outcomes cover additional domains such as weight, quality of life, gastrointestinal symptoms, anxiety, and depressive symptoms. The registry record does not post analyses for those secondary outcomes.
The pilot designation is relevant to interpretation because a small study can yield highly uncertain estimates even when it reports numerical group summaries. The total enrollment was 38, with 16 participants in the placebo group and 22 in the roflumilast group for the primary result. The registry does not report a sample-size justification, analysis plan, or inferential result. These gaps underline the value of reporting the intended analysis, participant flow, missing-data handling, and confidence intervals alongside outcome summaries.
For biostatisticians and clinical researchers, the record prompts a practical question: what information is needed to move from observed group summaries to a defensible estimate of a randomized contrast? A clear analysis method, defined analysis population, transparent missing-data accounting, and interval estimate would help answer it. Their absence limits the statistical conclusions that can be drawn, without making the descriptive results meaningless.
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 registry record leaves several trial-specific details unreported. It does not give the eligibility criteria beyond its description of poorly controlled asthma in adults with obesity, nor does it define how poor control was determined. The process for randomization, allocation concealment, and the roles covered by quadruple masking are not described. These details would help readers assess the conduct and applicability of the trial.
For the primary outcome, the record identifies a baseline-to-24-week change and describes an unadjusted comparison, but does not specify the statistical test or provide an inferential result. It also does not define the analysis population, report the number with an observed 24-week score, or describe missing-data handling. The results therefore cannot be assessed for attrition or sensitivity to analytic choices using the registry record alone.
The registry lists seven secondary outcomes but posts no analyses. It does not report how multiplicity was handled or whether a hierarchy of outcomes was specified. The sample-size justification and any interim analyses are not reported in the registry record. The stated planning-illustration assumptions do not establish which methods were used for trial design or analysis.
The primary outcome summaries are medians with interquartile ranges. Without individual-level distributions or the method used for the group comparison, readers cannot assess further distributional features or verify how the inferential analysis was conducted. The posted safety information gives counts and selected event terms, but does not include a comparative analysis or detail sufficient to assess exposure time or causal attribution. These limitations constrain interpretation of this record; they do not demonstrate that the unreported procedures were absent from the trial's conduct.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trial of Roflumilast in Asthma Management (TRIM) — NCT03532490.
- Registry record last updated 2022-10-06; status last verified 2022-09.
- Results first posted 2022-10-06.
- 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.
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18. Record Summary
TRIM, registered as NCT03532490, is a completed phase 2 randomized, quadruple-masked, parallel, placebo-controlled pilot trial sponsored by Johns Hopkins University. It enrolled 38 participants and concerns asthma and obesity. The registry lists a start date of 2018-08-03 and a primary completion date of 2021-07-30.
The primary outcome is change in Asthma Control Test score from baseline to 24 weeks, described as an unadjusted comparison. The posted median changes are 2.0 for placebo and 2.6 for roflumilast, with interquartile ranges of 0.7 to 3.3 and 0.5 to 4.4, respectively. The primary comparison's test, confidence interval, and p-value are not reported in the registry record.
Seven secondary outcomes are listed, but no analyses are posted. Safety reporting records serious adverse events in 0 of 16 placebo participants and 6 of 22 roflumilast participants, with no deaths reported in either group. Analysis populations, missing-data methods, the sample-size justification, and multiplicity procedures are not reported in the registry record.