Randomized Controlled Trial of Talc Instillation In Addition To Daily Drainage Through a Tunneled Pleural Catheter to Improve Rates of Outpatient Pleurodesis in Patients With Malignant Pleural Effusion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Controlled Trial of Talc Instillation In Addition To Daily Drainage Through a Tunneled Pleural Catheter to Improve Rates of Outpatient Pleurodesis in Patients With Malignant Pleural Effusion (NCT04792970), a randomized phase 4 study. The primary outcome is Percentage of Participants Undergoing Accelerated Pleurodesis.

2. Clinical Question

The trial’s stated purpose was to compare experiences under these two drainage approaches. Its title and primary outcome focus on outpatient pleurodesis, while the listed secondary outcomes include dyspnea and quality of life measured with the Short Form 36 Health Survey at baseline, 30 days, and 90 days. The registry record does not explain how “accelerated” pleurodesis was operationally defined, nor does it describe the criteria used to determine whether pleurodesis had occurred.

The posted primary-endpoint summaries are not a usable comparison of the randomized arms. The talc arm has no participants included in the endpoint analysis, while the standard-drainage arm has one participant and a reported percentage of 100.0%. Because the analysis includes only participants who underwent pleurodesis while on study, it does not represent all four enrolled participants. The registry record therefore does not establish a comparative estimate of the primary outcome.

3. Trial Design

The registry record identifies this as a phase 4, randomized, parallel-group trial with no masking. The two assigned approaches were talc instilled through a tunneled pleural catheter together with standard daily drainage, and standard daily drainage alone. The study was sponsored by Duke University and enrolled 4 participants. Its status is terminated. The recorded start date is 2021-03-18, and the recorded primary completion date is 2022-10-07.

Random assignment is intended, in general, to make treatment groups comparable on average, including for factors that are not measured. That protection depends on the trial having enough participants and on the assigned groups and outcomes being adequately documented. With only 4 participants enrolled, the randomized comparison is highly limited: even a valid allocation cannot ensure that the groups are balanced in a trial this small. The record does not report the allocation sequence method, concealment procedures, or reasons for termination, so those details cannot be assessed.

No masking was used. In general, an unmasked design means participants and study personnel know which approach is assigned. That knowledge can influence experiences, reporting, care decisions, or outcome assessment, depending on the endpoint and how it is measured. The registry record does not explain whether outcome assessors were kept unaware of assignment or how pleurodesis was assessed.

The registry record lists five outcome measures in total: the primary endpoint and four secondary outcomes. The secondary outcomes are dyspnea measured by questionnaire and quality of life measured by the Short Form 36 Health Survey at baseline, 30 days, and 90 days. The record does not report whether every listed measure was collected for every participant, or whether any of these secondary outcomes were analyzed. It lists no posted statistical analyses. The trial’s actual protocol, planned sample size, and rationale for that size 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Only participants who underwent pleurodesis while on study are included in the analysis

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 Percentage of Participants Undergoing Accelerated Pleurodesis, measured over Up to 90 Days.

The primary endpoint is the percentage of participants undergoing accelerated pleurodesis, assessed up to 90 days. It is a binary outcome summarized as a percentage: a participant either meets the outcome definition or does not. The registry description restricts the analysis to participants who underwent pleurodesis while on study. It does not specify the precise definition of “accelerated,” the event-assessment process, or the handling of participants whose status could not be determined.

In general, a percentage can make the frequency of an event easier to interpret than a raw count when the denominator is clear. The denominator matters because the same percentage can reflect very different amounts of information when it is based on different numbers of people. Here, the endpoint summaries include no participants in the talc arm and one participant in the standard-drainage arm. The 100.0% reported for the latter arm therefore describes that one-person analysis subset; it should not be read as a stable estimate for the full randomized group.

The endpoint aligns with the trial’s stated focus on outpatient pleurodesis. However, the record does not explain why this particular measure was chosen over other possible outcomes, or how it relates to the listed measures of dyspnea and quality of life. Since the endpoint comparison is not estimable from the posted arm summaries, the registry record does not give a comparative estimate of the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

How should a percentage endpoint be read?

For a binary outcome, each participant is classified according to whether the defined event occurred. A percentage expresses the event frequency among the participants included in the analysis. To interpret it, readers need both the percentage and its denominator, along with a clear definition of the event and the population counted. The registry describes the primary outcome as a percentage of participants undergoing accelerated pleurodesis up to 90 days, but does not define “accelerated” or provide assessment rules.

The posted endpoint summaries list no participants in the talc arm and one participant in the standard-drainage arm. The latter arm’s value is 100.0%. A percentage based on one participant is a description of that participant’s outcome, not a precise estimate of a broader population frequency. Since there is no endpoint value for the talc arm, a difference between the randomized groups cannot be estimated from these summaries. The registry record identifies the two-arm comparison as missing or not estimable.

Why does the analysis population matter?

The primary-endpoint description says the analysis includes only participants who underwent pleurodesis while on study. This is not the same as analyzing everyone assigned to each randomized arm. In general, the intent-to-treat principle compares participants according to their randomized assignment, regardless of what happens after assignment. It helps preserve the balance created by randomization. The record does not say that an intent-to-treat analysis was conducted.

Restricting an outcome analysis to participants who experienced a post-assignment event can change the question being answered. It can also make the groups less comparable, because the reasons participants enter that subset may be related to their subsequent course or to their assigned approach. The registry record does not describe how many participants underwent pleurodesis overall, why some participants do not appear in the endpoint summaries, or whether the endpoint population was defined in a protocol. The available summaries cannot resolve these issues.

What can confidence intervals and tests contribute?

In general, a confidence interval communicates statistical uncertainty around an estimated quantity. A narrow interval indicates greater precision under the assumptions of the method; a wide interval indicates less precision. A hypothesis test evaluates how compatible the observed data are with a specified null hypothesis under a statistical model. Neither a confidence interval nor a test can supply information missing from one arm of a comparison. No confidence interval, test statistic, or p-value for the primary-endpoint comparison is posted in the registry record.

For binary outcomes, methods for comparing groups depend on the observed counts, the analysis population, and the chosen statistical plan. Very sparse counts may make standard approximations unreliable, so an exact method or another approach may be considered in some settings. The appropriate choice depends on prespecified methods and the actual data. The registry record does not report a statistical analysis plan, a chosen method for the primary comparison, or an adjusted analysis. No method should be inferred from the endpoint percentages alone.

What do the planning illustrations mean?

In general, a sample-size calculation estimates how many participants a study would need under stated assumptions to detect a specified effect with a chosen significance level and power. Such calculations are planning tools, not evidence that a study had that power after enrollment, and they do not determine whether a result is clinically important. A planning illustration based on an observed effect also depends on the observed effect being estimable and meaningful as an input.

The described planning assumptions use 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. These are explicitly illustrative assumptions, not a report of the trial’s own design. The primary endpoint lacks an estimable two-arm effect in the posted summaries, so those summaries do not support a meaningful effect-based planning illustration for this comparison. Any participant count labelled participants per arm for 80% power would be a planning quantity, not an observed trial result or observed power. The registry record does not report the trial’s own sample-size justification.

Why does multiplicity matter?

When a study evaluates several outcomes or performs multiple statistical tests, the chance of at least one apparently unusual result can rise if each test is treated independently at the same threshold. Statistical plans can address this issue by identifying a primary outcome in advance, adjusting for multiple comparisons, or specifying a hierarchy of tests. The registry lists one primary outcome and four secondary outcomes, but does not report a multiplicity strategy or posted analyses of those outcomes. Therefore, no claim about multiplicity-adjusted inference can be made.

What does the safety summary measure?

The safety record gives the number at risk and the number affected for serious and other adverse events, along with deaths. These counts are descriptive. In general, adverse events occurring during a trial do not by themselves establish that the assigned intervention caused them. Causal assessment requires clinical context and methods not described in the registry summary. With 2 participants at risk in each arm, the listed counts provide limited information about the frequency or comparative safety of events in broader populations.

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.

R code and output

arm    <- c("Standard Daily Drainage")
n      <- c(1)
events <- c(1)
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  Standard Daily Drainage  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and four secondary outcomes. The secondary outcomes concern dyspnea measured by questionnaire and quality of life measured with the Short Form 36 Health Survey at baseline, 30 days, and 90 days. The record does not report a multiplicity strategy, such as an adjustment for testing several outcomes or a hierarchy specifying how results should be interpreted. It also lists 0 posted analyses. Consequently, no statistical findings for the secondary outcomes or multiplicity-adjusted conclusions are available in the registry record.

The primary endpoint analysis is limited to participants who underwent pleurodesis while on study. The registry record does not explain the handling of missing outcome information, participants who did not undergo pleurodesis, or participants whose endpoint status was unknown. It does not report imputation, sensitivity analyses, or other methods for assessing the effect of missing data. The endpoint summaries include 0 participants in the talc arm and 1 participant in the standard-drainage arm; the record marks a two-arm comparison as not estimable.

The analysis population for the secondary outcomes is not reported in the registry record. It is also not clear whether these measures were collected for every enrolled participant or how repeated measurements were to be analyzed. These omissions limit assessment of both missing-data risk and the intended interpretation of the secondary outcomes.

In general, missing data can affect validity when the likelihood of a measurement being absent is related to participant characteristics, assigned treatment, or the outcome itself. Statistical methods cannot fully eliminate uncertainty when the reasons for missingness and the relevant data are unavailable. Here, the small enrollment and incomplete endpoint summary make the potential impact especially difficult to assess. No assumptions about the missing outcomes or analyses should be treated as established.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnea (50.0%), suspected pleural catheter infection (50.0%).

The safety summary lists 2 participants at risk in each arm. Serious adverse events are recorded for 1 participant in the talc-plus-daily-drainage arm and 1 participant in the standard-drainage arm. The registry identifies dyspnea and suspected pleural catheter infection as the top serious-event terms, each reported as 50.0%. The record does not provide enough detail in these summaries to determine how the terms relate to the individual serious-event counts.

Other adverse events are recorded for 0 participants in the talc arm and 2 in the standard-drainage arm. Deaths are recorded for 1 participant in the talc arm and 0 in the standard-drainage arm. These figures are event summaries, not proof of cause. The registry record does not state that the death or any adverse event was caused by the assigned approach, and the small groups make the counts unsuitable as stable estimates of risk.

In general, adverse-event comparisons require attention to definitions, follow-up duration, severity, attribution, and the number of people observed. The record does not report detailed event narratives or an analysis of between-arm safety differences. The figures should therefore be read as descriptive observations from this small terminated trial, not as a reliable comparative safety assessment.

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

The registry record establishes that a randomized, parallel-group trial compared talc instillation through a tunneled pleural catheter plus daily drainage with standard daily drainage alone. It records 4 enrolled participants and a terminated status. It also records a primary endpoint concerning accelerated pleurodesis up to 90 days and lists secondary measures of dyspnea and quality of life. These details describe the study’s question and structure, but they do not amount to a usable estimate of the primary treatment contrast.

The primary endpoint summaries are not comparable across arms: the talc arm has no participants in the endpoint analysis, and the standard-drainage arm has one participant with a reported value of 100.0%. The value for the one-person subset cannot stand in for all participants assigned to standard drainage. Nor can it be compared with the talc arm, for which no endpoint value is posted. The registry marks the binary two-arm comparison as missing or not estimable.

As a result, these data do not establish whether one approach changed the chance or timing of pleurodesis relative to the other. They also do not establish the size, direction, or precision of a comparative effect. A missing comparison is not evidence that the approaches are equivalent, and a single-arm percentage is not evidence of a treatment effect.

The adverse-event counts describe what was recorded among the participants at risk, but they do not establish causation or provide a dependable comparison of safety. The registry record does not report the reason for termination, a full statistical plan, the sample-size rationale, or analyses of the secondary outcomes. Those gaps prevent broader conclusions about the intended outcomes and conduct of the trial.

In general, a randomized trial is most informative when its planned outcomes and analyses are reported for the assigned groups, with clear denominators and uncertainty estimates. The posted information is insufficient for that kind of comparative interpretation. It can be used to understand the trial’s design and the limits of its recorded results, but not to draw a conclusion about treatment benefit or lack of benefit.

14. Why This Trial Matters Statistically

This trial raises a basic statistical issue: randomization alone does not guarantee an interpretable result. Random assignment can support a fair comparison, but a useful estimate still requires outcome data for both groups, clear outcome definitions, and an analysis population that preserves the comparison of interest. The registry’s primary endpoint summaries include no talc-arm participants and one standard-drainage participant, so those requirements are not met for the posted primary comparison.

The contrast between the total enrollment of 4 and the endpoint population is also important. The endpoint description limits inclusion to participants who underwent pleurodesis while on study. That restriction makes the denominator central to interpretation and raises questions about how the endpoint subset relates to randomized assignment. The registry record does not provide enough detail to resolve those questions.

The trial also illustrates why sample-size planning and observed evidence must be kept distinct. General planning calculations can be based on assumptions about the effect to detect, allocation, and statistical method. They cannot substitute for a usable observed comparison. The registry record’s planning assumptions are illustrative, and the posted primary endpoint does not yield an estimable two-arm effect to serve as a sound basis for interpreting such a calculation. A planning quantity is not a description of the evidence collected.

Finally, the record lists several outcomes and descriptive safety counts without posting analyses of the outcomes. This makes transparent reporting of analysis methods, missing data, and outcome definitions especially consequential. Readers can identify the intended comparison and see why its primary result is limited, but cannot assess an adjusted treatment estimate, uncertainty around that estimate, or a multiplicity strategy. The statistical lesson is not a conclusion about either approach; it is that a randomized design can remain inconclusive when enrollment and outcome reporting do not support the planned comparison.

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.

The most direct limitation is the small enrollment: the registry records 4 participants. The primary endpoint analysis is smaller still, including 0 participants in the talc arm and 1 in the standard-drainage arm. With no endpoint value for one arm, the primary comparison is not estimable from the posted summaries. The 100.0% reported in the standard-drainage arm is based on one participant and should not be generalized to the full arm or to other settings.

The endpoint is described as accelerated pleurodesis, but the registry record does not define “accelerated” or report the criteria and process used to assess the outcome. The analysis includes only participants who underwent pleurodesis while on study, and the record does not explain the selection into that analysis population or the status of other enrolled participants. This makes the endpoint denominator and its relationship to randomized assignment difficult to assess.

The trial is recorded as terminated, but the reason is not reported in the registry record. The record also does not report the protocol, allocation-generation details, allocation concealment, sample-size justification, statistical analysis plan, missing-data procedures, or multiplicity strategy. No analyses are posted for the listed secondary outcomes. These gaps constrain evaluation of the study’s planned methods and the completeness of outcome reporting.

The safety summaries are based on 2 participants at risk in each arm and provide counts without enough detail for causal attribution or robust comparison. The open-label design is another interpretive limitation; the record does not explain whether outcome assessment was independent or masked. Together, these features mean the available results are descriptive and incomplete rather than a precise comparative assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Randomized Controlled Trial of Talc Instillation In Addition To Daily Drainage Through a Tunneled Pleural Catheter to Improve Rates of Outpatient Pleurodesis in Patients With Malignant Pleural Effusion — NCT04792970.
• Registry record last updated 2023-09-28; status last verified 2023-09.
• Results first posted 2023-09-28.
• 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.

19. Record Summary

NCT04792970 is a phase 4 randomized, open-label, parallel-group trial sponsored by Duke University. It compared talc instilled through a tunneled pleural catheter with standard daily drainage against standard daily drainage alone in participants with malignant pleural effusion. The record lists 4 enrolled participants, a terminated status, a start date of 2021-03-18, and a primary completion date of 2022-10-07.

The primary outcome was the percentage of participants undergoing accelerated pleurodesis up to 90 days, among participants who underwent pleurodesis while on study. The posted endpoint summary includes no participants in the talc arm and one in the standard-drainage arm, so a two-arm comparison is not estimable. Four secondary outcomes are listed, but the registry record posts 0 analyses. Safety counts are reported for 2 participants at risk in each arm and should be interpreted descriptively. The reason for termination, sample-size justification, statistical plan, and handling of missing outcome data are not reported in the registry record.