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 Propranolol Dose Escalation in Lymphedema in Patients (NCT02595996), a na phase 2 study. The primary outcome is Number of Patients That Tolerated Propranolol.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02595996 |
| Phase | Phase 2 |
| Condition | Primary Lymphedema |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Columbia University |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with primary lymphedema. The registry record lists an enrollment of 1. It also states that the study was terminated because of lack of funding and that data were not analyzed or disclosed because subject confidentiality was an issue.
Intervention
The intervention was propranolol, a drug administered in escalating doses according to the treatment description. The registry record does not give the dose levels, escalation schedule, or details of how exposure was completed.
Comparator
This was a single-group study, with allocation listed as not applicable and no masking. The registry record does not describe a placebo group, usual-care group, or other concurrent comparator. Changes therefore cannot be contrasted with outcomes in a control group.
Primary question
The primary question was whether patients tolerated propranolol over the stated timeframe of 8 weeks. Secondary questions concerned self-reported quality of life, fluid retention assessed by weight, lower limb discrepancy, and fluid retention assessed by MRI. These are intended questions, not reported findings: the record says the data were not analyzed or disclosed.
3. Trial Design
This was a phase 2, single-group, open-label study of propranolol dose escalation in patients with primary lymphedema. The registry lists allocation as not applicable and masking as none. The treatment description says patients would receive propranolol in escalating doses. Because there is no concurrent comparison group, the design does not provide a randomized treatment-versus-control contrast.
The registry lists enrollment as 1. It gives a start date of 2017-06-07 and a primary completion date of 2020-10-08, and records the study status as terminated. The stated reason for termination was lack of funding. The record does not report whether the enrolled participant completed dose escalation or follow-up, or which doses were received.
The primary outcome was the number of patients who tolerated propranolol, with a timeframe of 8 weeks. Secondary outcomes were framed as counts of patients with improved quality of life on self-reported questionnaires, decreased fluid retention by weight, lower limb discrepancy, and decreased fluid retention on MRI. The registry record does not report timeframes for those secondary outcomes.
The record states that data were not analyzed or disclosed because subject confidentiality was an issue. It lists no analyses. Thus, the study design and planned questions can be described, but the record does not provide an analyzed outcome set for judging tolerability or changes in signs and symptoms. A detailed protocol, dose-escalation rules, analysis plan, and sample-size justification 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
| Stage | Treatment |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Study terminated due to lack of funding. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=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.
| Characteristic | Unit | Treatment |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 1 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients That Tolerated Propranolol, measured over 8 weeks.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of patients who tolerated propranolol, assessed over 8 weeks. The registry description characterizes this as an assessment of whether patients tolerated the drug. It does not define a threshold or operational rule for what counted as tolerability, such as a symptom criterion, dose-limiting event, or treatment discontinuation. Those details are not reported in the registry record.
A tolerability endpoint is intended to capture whether participants can continue treatment under the study conditions. In general, this can help distinguish an intervention that can be taken as planned from one that leads to unacceptable difficulties. That general purpose does not establish that a particular participant tolerated treatment; interpretation requires the prespecified definition, exposure information, follow-up status, and analyzed outcome.
The endpoint is expressed as a patient count rather than a measurement of symptom change. The registry record does not disclose an analyzed count or a numerator and denominator for the primary result. Although the record lists enrollment as 1, it says the data were not analyzed or disclosed because of subject confidentiality. The endpoint therefore remains an intended measure rather than an interpretable reported result.
The secondary outcomes addressed quality of life and physical signs of lymphedema, including fluid retention and limb discrepancy. They could complement tolerability by describing different dimensions of the condition, but the record gives no analyzed values for them.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study intended to evaluate escalating propranolol doses in primary lymphedema, but it does not report analyzed clinical outcomes. It explicitly states that the study was terminated because of lack of funding and that data were not analyzed or disclosed because subject confidentiality was an issue. Consequently, there is no posted estimate of how many patients tolerated propranolol, and no reported result for the secondary measures.
Enrollment is listed as 1. That small enrolled cohort means the design could at most describe the experience recorded for the enrolled participant; it cannot provide a stable estimate of outcomes across a broader patient population. In this case, even an individual outcome is not reported. It would be incorrect to treat the lack of disclosed results as evidence that the participant did or did not tolerate treatment, or that lymphedema signs changed or remained unchanged.
The single-group design also limits causal interpretation. In general, when outcomes are measured only in a treated group, observed changes cannot be separated from natural variation, measurement variation, concurrent care, or other influences using a randomized control contrast. The registry lists no comparator arm, so there is no reported between-group effect to interpret. The escalating-dose approach may have been intended to observe tolerability as exposure changed, but the record does not report actual dose levels, timing, participant exposure, or dose-specific outcomes.
No effect estimate, uncertainty interval, hypothesis test, or analysis result is listed. The registry records zero analyses. Without an analyzed outcome, statistical precision cannot be assessed, and a result cannot be characterized as statistically significant or not statistically significant. No estimate should be reconstructed from the enrollment or adverse-event counts: these do not substitute for an analyzed endpoint, particularly when the record says outcomes were withheld.
The posted safety figures list 1 at risk for serious adverse events and 0 affected; for other adverse events, 1 at risk and 0 affected; and 0 deaths. These counts are descriptive registry entries, not a complete safety analysis. They do not resolve the absence of disclosed outcome data, nor do they establish that no harms occurred outside the recorded categories or observation period.
Overall, the record supports conclusions about the study's intended design, its termination, and the absence of disclosed analyses. It does not support an efficacy estimate, a definitive tolerability conclusion, or a comparison with another treatment. Those distinctions matter: lack of an analyzed result is not evidence of no effect, and a planned clinical question is not itself a finding.
9. Statistical Methods Explained
The registry describes a phase 2, single-group study with no masking. In general, a single-group study can describe outcomes among treated participants, but it does not directly estimate how outcomes would have differed under a concurrent alternative. Here, allocation is listed as not applicable and no control group is recorded. The study therefore has no randomized contrast for separating treatment-associated changes from other changes over time.
What does dose escalation add?
In general, dose escalation can be used to observe tolerability as exposure increases. Interpreting such observations requires knowing the doses, order and timing of dose changes, rules for pausing or stopping treatment, and the participant's exposure and follow-up. The registry says propranolol was to be given in escalating doses, but those operational details are not reported in the registry record. The record also does not say whether the enrolled participant completed the intended escalation.
The primary endpoint was a count of patients who tolerated propranolol over 8 weeks. A count needs a clear outcome definition and a known assessment population to be interpretable. The record does not state the operational definition of tolerance, disclose the analyzed outcome, or explain how incomplete follow-up would have been handled. Its description says data were not analyzed or disclosed because subject confidentiality was an issue.
What can uncertainty measures show?
In general, a confidence interval describes the range of values compatible with an estimate under a statistical model and sampling assumptions. Wider intervals indicate less precision; narrower intervals indicate greater precision, subject to the model. No interval or underlying analyzed estimate is reported for this trial, so precision cannot be assessed from the registry record. A p-value would address compatibility with a specified null model, not the size or clinical importance of an effect. No p-value or hypothesis test is reported.
Counts can be informative when the event definition and denominator are clear. In general, a small denominator makes each observation influential and can leave substantial uncertainty about the rate in a wider population. The enrollment is 1, and no analyzed primary outcome is disclosed. It is therefore not possible to estimate a population tolerability rate from the record. The posted adverse-event counts should likewise be read as descriptive entries rather than as precise estimates of risk.
Why does the comparison structure matter?
For a randomized comparison, treatment groups can provide a basis for estimating a contrast, subject to the design and analysis assumptions. This study has no like-for-like control comparison. Even if a before-and-after measurement had been reported, general statistical reasoning would not treat that change alone as a controlled treatment effect: time trends, measurement variation, and other influences could also contribute. The registry record does not report analyzed before-and-after values for the secondary outcomes.
Different outcome types also call for different analytical approaches. In general, a binary endpoint such as whether a participant met a tolerability criterion may be summarized by counts, while repeated measurements or continuous measures may require methods that reflect their scale and timing. Repeated observations from one person are not independent observations. Methods for counts may also need to account for over-dispersion when variability exceeds what a simple model assumes. These are general considerations, not methods reported as used in this study; the registry record lists no analyses and does not provide a statistical analysis plan.
The record includes a planning-illustration description based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect, and distinguishes participant counts per arm from total event counts for time-to-event settings. These are planning assumptions, not the study's own design or observed power. The actual trial is recorded as single-group, and the registry does not report a sample-size justification or an analyzed observed effect. No numerical planning result can be interpreted as a result of this trial.
Most importantly, the method actually used to analyze clinical outcomes is not reported in the registry record. With no disclosed outcome analysis, there is no basis for reproducing or evaluating an effect estimate, checking model assumptions, or judging statistical precision.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 5 outcome measures: the primary tolerability outcome and secondary measures concerning self-reported quality of life, fluid retention by weight, lower limb discrepancy, and fluid retention on MRI. Multiple outcomes can raise a multiplicity issue when several statistical tests are conducted. In general, testing many hypotheses without an adjustment or a prespecified hierarchy can increase the chance of at least one apparently positive result arising by chance. The registry record does not report whether multiplicity was considered, whether outcomes were prioritized beyond the primary designation, or whether any adjustment was planned.
The record lists 0 analyses and states that data were not analyzed or disclosed because subject confidentiality was an issue. It therefore does not provide outcome estimates, test results, or an account of any multiplicity procedure. The absence of reported analyses should not be interpreted as a correction for multiple testing or as evidence that the outcomes were equivalent.
Missing-data methods and analysis populations are not reported in the registry record. It does not specify an intention-to-treat, per-protocol, safety, or other analysis population, nor does it say how incomplete outcome assessments, early treatment discontinuation, or missing questionnaire or imaging data would have been handled. The record's statement about confidentiality explains why data were not disclosed; it does not establish the extent or statistical treatment of missingness.
In general, missing-data assumptions can affect estimates because participants with observed outcomes may differ from those without them. That concern cannot be evaluated: there are no disclosed outcome-level data or documented analysis rules. No imputation approach, sensitivity analysis, or missingness summary is reported in the registry record.
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 |
|---|---|---|---|
| Treatment | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment | 0 of 1 |
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 |
|---|---|
| Treatment | 0 of 1 |
The posted adverse-event figures list the Treatment group with 1 at risk for serious adverse events and 0 affected. For other adverse events, the record lists 1 at risk and 0 affected. Deaths are listed as 0. These are the safety counts recorded in the registry; they should be read as descriptive figures, not as a full account of safety.
A count of 0 affected in a group with 1 at risk does not demonstrate that a treatment has no risk. In general, safety summaries depend on the exposure received, length and completeness of follow-up, event definitions, and the way events were collected. The registry record does not provide detailed exposure or follow-up information, a list of non-serious adverse-event terms, or a fuller safety analysis. It also states that data were not analyzed or disclosed because of subject confidentiality.
The figures therefore do not establish that no adverse events occurred in all circumstances, nor do they establish a reliable rate for a broader population. They do not replace the missing primary tolerability result. Tolerability was the stated primary question, but the registry record does not disclose its analyzed outcome.
12. What the Result Does, and Does Not, Mean
The record establishes that the study was designed to examine escalating doses of propranolol in primary lymphedema, with tolerability as the primary question and several symptom or sign measures as secondary questions. It also establishes that the study was terminated because of lack of funding, lists enrollment as 1, and states that data were not analyzed or disclosed because subject confidentiality was an issue.
What the record does not establish is whether propranolol was tolerated, whether quality of life changed, or whether fluid retention or limb discrepancy changed. No analyzed primary or secondary outcome values are reported. The absence of those results is not a negative finding. It cannot be interpreted as showing that treatment had no effect, that it caused an effect, or that the enrolled participant experienced a particular outcome.
The single-group structure also means that the record does not contain a randomized comparison with another treatment or control condition. In general, an uncontrolled observation cannot isolate the causal contribution of treatment from other influences. Here, the lack of outcome data means even descriptive change cannot be assessed.
The adverse-event counts are limited descriptive information: 1 at risk and 0 affected for serious events, 1 at risk and 0 affected for other events, and 0 deaths. They are not sufficient to establish safety or estimate risk with useful precision. A small cohort and unavailable analyzed outcomes make broad conclusions especially unsupported.
The appropriate interpretation is therefore narrow: the registry documents the study's intended questions and design, its termination, and the absence of disclosed analyses. It offers no interpretable efficacy result and no definitive tolerability result. Any claim that propranolol did or did not improve lymphedema, or was or was not tolerated, would go beyond what the registry record reports.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a clinical question and an analyzable result. The study asked whether patients tolerated escalating propranolol doses and whether lymphedema signs or symptoms changed. But the record says the study ended because of lack of funding and that data were not analyzed or disclosed because subject confidentiality was an issue. Without outcome results, the intended questions cannot be answered from the registry record.
The design also highlights the limits of a single-group study. Such a design can be useful for describing observations under treatment, but it lacks a concurrent control contrast. Even a reported change over time would require cautious interpretation because the design alone cannot distinguish treatment effects from other influences. In this record, no such change is reported.
Enrollment of 1 underscores the distinction between a participant-level observation and a population-level estimate. General statistical inference depends on both the amount of information and the design's ability to support the intended comparison. Here, there is no disclosed analyzed outcome from which to quantify uncertainty or assess consistency.
Finally, the record demonstrates why transparency about endpoints, definitions, analysis populations, missing data, and statistical methods is important. These details help readers understand how a planned question became an estimate and what assumptions support it. They are not reported in the registry record, and the absence of analyses prevents independent assessment. The lesson is methodological rather than a conclusion about propranolol: planned outcomes and safety counts should not be mistaken for evidence of a treatment effect.
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 most consequential limitation is that the registry record reports no analyzed or disclosed outcome data. It gives no primary endpoint result and no results for the secondary outcomes. This prevents evaluation of tolerability, changes in lymphedema measures, or statistical precision.
Enrollment is listed as 1, limiting the amount of information even if an outcome had been disclosed. A single-group design also has no concurrent comparator, so it cannot provide a randomized contrast. The record does not report actual doses, dose timing, exposure, adherence, completion of escalation, or follow-up beyond the primary endpoint's stated 8 weeks.
Important measurement details are also absent. The registry does not define the criterion for tolerability, explain how changes in quality of life or physical measures were assessed, or report timeframes for the secondary endpoints. It does not report a statistical analysis plan, sample-size justification, analysis populations, missing-data approach, or multiplicity procedure. These omissions make it impossible to judge the intended analysis or whether the planned outcomes were assessed as described.
The adverse-event summary is limited to the posted counts and does not include event terms or detailed exposure and follow-up context. Those counts cannot support a comprehensive safety assessment. The registry's confidentiality statement explains why data were not disclosed, but the record does not provide further detail about the extent of unavailable data or how it affected interpretation.
The study's termination due to lack of funding is relevant to the absence of reported analyses, but the registry does not report further operational details. Together, the missing outcomes, limited enrollment, absence of a comparator, and incomplete methodological information preclude efficacy or definitive tolerability conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Propranolol Dose Escalation in Lymphedema in Patients — NCT02595996.
- Registry record last updated 2021-10-22; status last verified 2021-09.
- Results first posted 2021-10-22.
- 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
The registry record describes a phase 2, open-label, single-group study of escalating propranolol doses in patients with primary lymphedema. Its primary outcome was the number of patients who tolerated propranolol over 8 weeks. Secondary outcomes concerned self-reported quality of life, fluid retention by weight, lower limb discrepancy, and fluid retention on MRI.
Enrollment is listed as 1. The study began on 2017-06-07, has a primary completion date of 2020-10-08, and is recorded as terminated because of lack of funding. The registry states that data were not analyzed or disclosed because subject confidentiality was an issue, and lists 0 analyses.
Posted safety counts are 1 at risk and 0 affected for serious adverse events, 1 at risk and 0 affected for other adverse events, and 0 deaths. No analyzed tolerability or lymphedema outcome is reported. The record therefore describes the study's purpose and status but does not provide a clinical outcome estimate.