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 Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF) (NCT02598193), a na phase 4 study. The primary outcome is Percentage of Participants Who Complete 24 Weeks of Combination Treatment on Pirfenidone at a Dose of 1602-2403 mg/Day and Nintedanib at a Dose of 200-300 mg/Day.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02598193 |
| Phase | Phase 4 |
| Condition | Idiopathic Pulmonary Fibrosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 89 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants had idiopathic pulmonary fibrosis and had received pirfenidone at a stable dose for at least 16 weeks before study entry. The primary endpoint’s safety population included participants who received at least one dose of investigational medicinal product on or after Day 1.
Intervention
Nintedanib was added to ongoing pirfenidone. The study description gives pirfenidone dosing of 1602-2403 mg/day and nintedanib dosing of 200-300 mg/day, with combination treatment planned for up to 24 weeks.
Comparator
There was no separate comparator group. This was a single-group, open-label study, so the posted results describe participants receiving the combination rather than a contrast between treatment groups.
Primary question
The primary endpoint asked what percentage of participants completed 24 weeks of combination treatment at the specified pirfenidone and nintedanib doses. The registry identifies Week 24 as the assessment time, but the primary endpoint result is not reported in the registry record.
3. Trial Design
This was a Phase 4, multicenter, exploratory, open-label, single-group study of pirfenidone in combination with nintedanib in participants with idiopathic pulmonary fibrosis. The registry lists an enrollment of 89 and a completed study. Its listed start date is 2016-01-14, and its primary completion date is 2017-05-16.
Eligible participants had already received pirfenidone at a stable dose for at least 16 weeks. Nintedanib was added on Day 1, and combination treatment was planned for up to 24 weeks. The arm description gives pirfenidone at 1602-2403 mg/day and nintedanib at 200-300 mg/day. The record does not provide further detail about dose changes, treatment interruptions, or the handling of participants who stopped one or both treatments.
Because the study had a single group and no masking, participants and study personnel were not blinded to the treatment being taken. The record does not describe a randomized allocation process; allocation is listed as not applicable. This design can describe treatment completion and safety outcomes among participants receiving the combination, but it does not create a concurrent control group for comparing those outcomes with another treatment or with no added treatment.
The primary endpoint was the percentage of participants who completed 24 weeks of combination treatment at the specified doses. The registry also lists outcomes concerning adverse and serious adverse events, discontinuation because of adverse events before the Week 24 visit, days on combination treatment, and time from starting combination treatment to discontinuation. Results for the primary endpoint and most secondary outcomes are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: At the start of screening, participants were on pirfenidone for at least 16 weeks and on a stable dose (1602-2403 mg/d) for at least 28 days. A total of 109 participants were screened, 20 participants were screen failures and 89 were enrolled at 36 study centers in 8 countries.
Overall Study
| Stage | Pirfenidone+Nintedanib |
|---|---|
| STARTED | 89 |
| COMPLETED | 73 |
| NOT COMPLETED | 16 |
Reasons for not completing this period:
| Reason | Pirfenidone+Nintedanib |
|---|---|
| Adverse Event | 13 |
| Withdrawal by Subject | 1 |
| Listed in active lung transplant list | 1 |
| Does not want to take Nintedanib | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
| Characteristic | Unit | Pirfenidone+Nintedanib |
|---|---|---|
| Participants analysed | 89 | |
| Age, Continuous | Years | 68.2 (SD 6.82) |
| Sex: Female, Male: Female | Participants | 18 |
| Sex: Female, Male: Male | Participants | 71 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 9 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 74 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 6 |
| Race/Ethnicity, Customized: White | Participants | 84 |
| Race/Ethnicity, Customized: Black or African American | Participants | 3 |
| Race/Ethnicity, Customized: Asian | Participants | 1 |
| Race/Ethnicity, Customized: Asian/White | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants Who Complete 24 Weeks of Combination Treatment on Pirfenidone at a Dose of 1602-2403 mg/Day and Nintedanib at a Dose of 200-300 mg/Day, measured over Week 24.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint measures the percentage of participants who completed 24 weeks of combination treatment while taking pirfenidone at 1602-2403 mg/day and nintedanib at 200-300 mg/day. It is a treatment-completion measure, not a direct measure of change in symptoms, lung function, or disease progression. The registry identifies Week 24 as the endpoint timeframe and defines the safety population as participants who received at least one dose of investigational medicinal product on or after Day 1.
Completion can be useful in a safety and tolerability study because it describes whether participants remained on the specified combination through the planned treatment period. It may capture the combined influence of tolerability, participant decisions, and other reasons for stopping or changing treatment. Completion alone does not identify why a participant did or did not finish, and it does not establish that any treatment caused a particular outcome.
The percentage and its stated 95% confidence interval are not reported in the registry record. Without those results, the endpoint’s observed level and its precision cannot be assessed from the record. The endpoint also has no randomized comparator in this study, so it cannot estimate a between-group difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a single group receiving pirfenidone with nintedanib and lists enrollment of 89. The primary question concerns completion of 24 weeks of combination treatment at the specified doses. However, the record does not report the observed percentage of participants who met that endpoint or its stated 95% confidence interval. The primary result therefore cannot be quantified or judged for precision from the registry record.
Safety information is reported for the combination group. The registry lists 16 participants with serious adverse events among 89 at risk, and 83 with other adverse events among 89 at risk. It reports zero deaths. The listed serious-event terms include pneumothorax at 3.4%, idiopathic pulmonary fibrosis at 2.2%, and pneumomediastinum, cholecystitis infective, influenza, and pneumonia at 1.1% each. These figures describe recorded events in this study; they do not establish that the treatment caused an event. The registry does not provide a comparator group, and the event terms should be read as safety reporting rather than causal estimates.
The record lists secondary outcomes on treatment discontinuation because of adverse events before the Week 24 visit, total participant days on combination treatment, and days from treatment initiation to discontinuation. Numerical results for these outcomes are not reported in the registry record. The number of outcome measures is listed as 5, but the record lists no analyses. Without reported endpoint results, analysis methods, or participant-level outcome detail, those outcomes cannot be independently assessed from this entry.
In general, a confidence interval conveys uncertainty around an estimated quantity: a narrower interval indicates greater precision under the method used, while a wider interval indicates less precision. Here, the primary interval is named in the endpoint description but its limits are not reported. No precision assessment can therefore be made. The record also does not report a treatment-effect estimate from a comparison, because the study is single-group and has no control arm.
These findings are descriptive of participants enrolled in this open-label study and the recorded treatment period. They should not be interpreted as a randomized comparison, a causal estimate, or evidence that the combination is more or less effective than another approach. The registry record does not report the primary completion result needed to describe how often participants met the main treatment-completion endpoint.
9. Statistical Methods Explained
Several statistical ideas help clarify what the registry entry can and cannot establish. The record names a percentage endpoint and a 95% confidence interval, but it does not report the endpoint estimate, the interval limits, or analysis procedures. The explanations below describe general statistical concepts rather than methods confirmed for this study.
What does a percentage endpoint describe?
In general, a percentage for a binary outcome describes the share of a defined analysis population meeting a stated condition. For this primary endpoint, the condition is completion of 24 weeks of combination treatment at the specified doses. To interpret such a percentage, readers need to know both the number meeting the condition and the population used as its denominator. The registry defines the primary endpoint population as the safety population: participants who received at least one dose of investigational medicinal product on or after Day 1. The actual primary percentage and its underlying count are not reported in the registry record.
A completion endpoint is different from a measure of treatment benefit. It says whether the specified treatment period was completed, not whether symptoms or disease status improved. If participants stop treatment, the reasons matter for interpretation. The registry lists discontinuation because of adverse events as a secondary outcome, but its result is not reported. Other reasons for discontinuation and the approach to incomplete endpoint information are not reported in the registry record.
What does a confidence interval add?
In general, a confidence interval expresses the statistical uncertainty around an estimate. It reflects how compatible a range of values is with the observed data under the method’s assumptions. It does not guarantee that the true value lies within that particular interval, and it does not account automatically for design limitations or bias. The primary endpoint is described with a 95% confidence interval, but the interval itself is not reported. Its width, and therefore the estimate’s precision, cannot be evaluated from this entry.
Confidence intervals for percentages can be calculated using different methods, especially when data are sparse or a percentage is near a boundary. The registry does not identify the method used for the primary interval. It also does not report whether any adjustment or other handling was applied to the percentage estimate. Those details should not be inferred from the endpoint label alone.
Why does the single-group design matter?
In general, a control group provides a concurrent reference for distinguishing outcomes under one treatment strategy from outcomes under another. This study is listed as single-group, open-label, and without a randomized comparison. Consequently, the posted results can describe what was recorded among participants receiving the combination, but they cannot estimate a randomized between-group contrast. Changes over time or events during treatment could also reflect factors other than the combination itself. No causal effect can be isolated by a comparison that the design does not include.
Open-label means treatment assignment was not masked. In general, awareness of treatment can influence reporting, participant decisions, clinical management, and judgments about outcomes. That possibility is relevant when interpreting treatment continuation and reported adverse events. The registry does not describe additional procedures to reduce or assess such influences.
What can the adverse-event summaries tell readers?
In general, an adverse-event percentage reports how commonly participants were recorded as having an event under a defined event and population rule. A serious adverse event is a category based on seriousness criteria, not necessarily a judgment that the study treatment caused the event. The registry reports serious and other adverse-event participant counts for the combination group and lists selected serious-event terms with percentages. It does not report a control-group rate, and the event summaries cannot establish comparative risk or causation.
Event-term percentages and participant counts are also not interchangeable with a complete account of event burden. A participant may experience more than one event, and the record does not give event-level counts for the listed terms. The registry’s figures should therefore be interpreted according to what they report: participants with serious or other adverse events, and selected terms with stated percentages. The record does not provide further detail on event coding, severity grading, or attribution.
What does the sample-size framework mean?
In general, planning calculations estimate how many participants a future study might need to detect a specified effect under chosen statistical assumptions. They are not observed outcomes and are not a measure of the probability that the study’s findings are correct. The registry describes a planning framework based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the planning effect is a stated fraction of the observed effect. The registry also distinguishes calculations for time-to-event outcomes from those for other outcomes.
That framework is not a description of this study’s design: this trial is single-group, not a two-arm randomized comparison. The record does not report the calculated planning values or a trial-specific sample-size justification. Such planning assumptions cannot replace the missing primary endpoint result, and they should not be interpreted as observed power.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Pirfenidone+Nintedanib | 89 | 69 | 77.5% | 67.4% to 85.7% | 67.8% to 85.0% | 67.8% to 84.9% |
R code and output
arm <- c("Pirfenidone+Nintedanib")
n <- c(89)
events <- c(69)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Pirfenidone+Nintedanib 89 69 77.5 67.4 85.7 67.8 85.0 67.8 84.911. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and secondary outcomes, but it does not report statistical analyses. It also does not describe a multiplicity strategy. In general, testing several outcomes can increase the chance of finding at least one apparently notable result by chance if each is assessed independently. Researchers may address this issue through prespecified testing sequences, adjustment procedures, or by treating secondary findings as exploratory. Which approach, if any, was used for this study is not reported in the registry record.
The registry identifies the primary endpoint population as the safety population, including participants who received at least one dose of investigational medicinal product on or after Day 1. The record does not describe other analysis populations or state whether the primary endpoint was analyzed using that population. The meaning of the safety population is given, but the primary endpoint’s actual denominator and result are not reported.
Missing-data handling is not reported in the registry record. In general, the way missing endpoint information is treated can affect a percentage estimate, particularly when completion is the outcome. Without the number of participants with missing Week 24 information, reasons for missingness, or a stated analysis rule, readers cannot assess how incomplete observations might affect the primary result.
The registry lists 5 outcome measures and 0 analyses. It provides no inferential analysis plan, model specification, or adjustment details. These omissions do not establish that no analyses were conducted; they mean that analysis methods and results are not reported in this registry record. No unreported statistical plan or missing-data approach should be inferred.
12. 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 |
|---|---|---|---|
| Pirfenidone+Nintedanib | 16 | 89 | 18.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pirfenidone+Nintedanib | 0 of 89 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pirfenidone+Nintedanib | 83 of 89 |
Most frequent serious adverse event terms
| Event term | Organ system | Pirfenidone+Nintedanib |
|---|---|---|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 3 of 89 |
| Idiopathic pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | 2 of 89 |
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | 1 of 89 |
| Cholecystitis infective | Infections and infestations | 1 of 89 |
| Influenza | Infections and infestations | 1 of 89 |
| Pneumonia | Infections and infestations | 1 of 89 |
| Tracheobronchitis | Infections and infestations | 1 of 89 |
| Invasive ductal breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 89 |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 89 |
| Pancreatitis | Gastrointestinal disorders | 1 of 89 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pirfenidone+Nintedanib |
|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 52 of 89 |
| Nausea | Gastrointestinal disorders | 44 of 89 |
| Vomiting | Gastrointestinal disorders | 29 of 89 |
| Cough | Respiratory, thoracic and mediastinal disorders | 20 of 89 |
| Fatigue | General disorders | 14 of 89 |
| Decreased appetite | Metabolism and nutrition disorders | 14 of 89 |
| Headache | Nervous system disorders | 13 of 89 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 10 of 89 |
| Dizziness | Nervous system disorders | 9 of 89 |
| Viral upper respiratory tract infection | Infections and infestations | 9 of 89 |
Serious events with the highest arm-level rate: pneumothorax (3.4%), idiopathic pulmonary fibrosis (2.2%), pneumomediastinum (1.1%), cholecystitis infective (1.1%), influenza (1.1%).
The registry reports 16 participants with serious adverse events among 89 at risk in the pirfenidone-plus-nintedanib group, and 83 with other adverse events among 89 at risk. It reports zero deaths. The term-specific serious-event percentages listed are pneumothorax at 3.4%, idiopathic pulmonary fibrosis at 2.2%, and pneumomediastinum, cholecystitis infective, influenza, and pneumonia at 1.1% each.
These numbers are descriptive safety results from a single-group study. The record does not provide a control group, so the figures do not estimate how event rates compare with another treatment or with no combination treatment. The listed event terms do not show that treatment caused the events. Nor do the term percentages provide a complete event-by-event account: the registry does not report counts for each listed term or whether participants experienced multiple events.
The serious-event participant count and other-event participant count refer to different event categories. The record does not report further details on severity beyond seriousness, event attribution, or the timing of each event. Accordingly, these figures describe recorded participant experience in the study, while leaving comparative risk and causal interpretation unresolved.
13. What the Result Does, and Does Not, Mean
The record establishes the study’s central question: whether participants already taking stable pirfenidone completed 24 weeks after nintedanib was added. It also documents an open-label, single-group design and provides selected safety results for the combination group. These features make the entry useful for understanding what was studied and the kinds of outcomes recorded.
However, the primary endpoint percentage and its 95% confidence interval are not reported in the registry record. Readers therefore cannot determine from this entry how many participants met the completion endpoint, how large the estimated percentage was, or how precise that estimate might be. The record also does not report numerical results for the listed discontinuation and treatment-duration outcomes.
The safety figures describe adverse events recorded among participants receiving the combination. They do not show whether those events were more common than under another treatment, because no comparator group was included. They also do not prove that the combination caused an event. The zero deaths reported in the record is a descriptive observation for this study, not a comparative estimate.
In general, a single-group study can provide information about treatment experience in its enrolled participants, but it cannot separate treatment effects from other influences in the way a well-conducted randomized comparison is designed to do. Its open-label nature also means that participants and study personnel knew the treatment being taken. The registry does not report methods addressing potential influences of that awareness.
Overall, the record supports a description of the study design and selected safety counts, but not a quantitative conclusion about the primary completion endpoint or a comparative treatment effect. Missing endpoint results, analysis details, and information on missing data limit further interpretation.
14. Why This Trial Matters Statistically
This study is statistically notable because its primary question is framed as treatment completion in a single group rather than as a comparison of treatment effects. That framing matters: a completion percentage can describe whether participants remained on a specified regimen for the planned period, but it cannot establish how completion would compare under an alternative strategy without a concurrent comparator.
The record also illustrates why a named endpoint and a confidence-interval label are not enough for interpretation. The primary endpoint is clearly described, and its intended population and timeframe are stated, but its estimate and interval are not reported. Without those results, readers cannot assess either the observed completion level or its precision. The design description alone cannot fill that gap.
Safety summaries raise a related issue. Counts of participants with serious and other adverse events describe what was recorded, while selected event terms provide additional context. In a single-group study, those observations do not yield comparative risk estimates. They should not be converted into claims about causation or treatment advantage.
Finally, the registry lists secondary outcomes and a planning framework but no analyses. Distinguishing planning assumptions from observed results is essential: sample-size planning does not substitute for a reported endpoint, and it is not observed power. For readers assessing evidence, the clearest statistical conclusion is therefore about the limits of what this record reports: design and selected safety information are available, while the primary endpoint result and analysis details are not.
15. 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 are specific to the design and reporting of this study. It was open-label and single-group, with no like-for-like control comparison. As a result, the registry can describe outcomes during combination treatment, but cannot separate treatment-related effects from other influences through a randomized between-group contrast. Awareness of treatment may also affect reporting or decisions about continuing treatment; the record does not describe methods used to address this possibility.
The primary endpoint result is not reported in the registry record, even though the endpoint and its 95% confidence interval are specified. This prevents assessment of the observed completion percentage and its precision. Numerical results for the secondary discontinuation and treatment-duration outcomes are also not reported. The registry lists no analyses and does not state the statistical methods used for these outcomes.
Important details for interpreting incomplete follow-up are not reported. The record does not describe missing-data handling, reasons for non-completion, or the number of participants with missing Week 24 endpoint information. It also does not report whether dose changes, interruptions, or discontinuations were handled in a particular way for the primary endpoint.
The adverse-event information is limited to participant counts and selected serious-event terms with percentages. The registry does not report counts for each term, event timing, attribution, or further coding and severity details. Because there is no comparator, the listed figures cannot provide comparative safety estimates. The record’s limitations should be kept in view when interpreting its descriptive findings.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF) — NCT02598193.
- Registry record last updated 2018-06-13; status last verified 2018-05.
- Results first posted 2018-06-13.
- 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.
Continue through the Clinical Biostats statistical pathway
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19. Record Summary
The registry describes NCT02598193, a completed Phase 4, multicenter, exploratory, open-label, single-group study sponsored by Hoffmann-La Roche. It enrolled 89 participants with idiopathic pulmonary fibrosis who had received stable pirfenidone before nintedanib was added on Day 1. Combination treatment was planned for up to 24 weeks.
The primary endpoint was the percentage completing 24 weeks of combination treatment at the specified doses. Its result and 95% confidence interval are not reported in the registry record. The safety results list 16 participants with serious adverse events, 83 with other adverse events, and zero deaths. No analyses are listed. With no comparator group, the posted safety figures are descriptive rather than comparative.