A Study Evaluating ClariVein With a Sclerosing Agent for the Treatment of Venous Insufficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating ClariVein With a Sclerosing Agent for the Treatment of Venous Insufficiency (NCT03311269), a randomized phase 2 study. The primary outcome is Patient-Reported Symptoms 7-Day Symptom Questionnaire (Heaviness, Achiness, Swelling, Throbbing & Itching) to Evaluate Improvement in Subject Reported Symptoms..

2. Clinical Question

The study is described as a prospective, randomized, controlled, multicenter, double-blind trial. Its primary endpoint was improvement in a five-symptom questionnaire score from baseline to post-treatment Week 12. The score was built from symptom responses, with lower scores representing better daily health outcomes. The posted results include arm-level means and standard deviations, along with analyses labeled as t-tests and an ANCOVA.

The trial enrolled 19 participants and was terminated. The registry record does not report why it was terminated, the number who completed the 12-week assessment, or the analysis population used for the posted endpoint results. Those omissions matter when interpreting a small trial: the arm summaries and statistical tests describe the available posted results, but do not by themselves establish how representative those results are of everyone enrolled.

The central statistical question is not whether either score changed in isolation, but how the recorded symptom outcomes compare across the randomized groups and how uncertain that comparison is. The reported analyses give different estimates, including a two-group t-test and an ANCOVA. The registry record does not explain the full relationship between these analyses, so they should be read according to their stated methods rather than treated as interchangeable answers to one fully specified analysis plan.

3. Trial Design

This was a Phase 2, randomized, parallel-group study described as prospective, controlled, multicenter, and double blind. The trial compared ClariVein RES with STS 1% against ClariVein RES with STS 3%. Each arm description specifies a single administration. The registry record identifies the device and the two drug interventions, but does not provide further details about the administration procedure in the information.

The registry records enrollment of 19 participants: 10 in the 1% arm and 9 in the 3% arm. The study started on 2017-09-22, had a primary completion date of 2018-05-15, and its status is terminated. The reason for termination is not reported in the registry record. Nor is the record information used for this analysis sufficient to establish how many participants contributed to each endpoint analysis or whether the arm summaries include all randomized participants.

Double masking is stated, but who was masked and how masking was maintained are not reported in the registry record. Details of the randomization sequence, allocation concealment, and any stratification are also not reported. These design features cannot be inferred from the terms randomized or double blind alone.

The primary endpoint was a patient-reported symptom score at 12 weeks compared with baseline. Elimination of saphenous vein reflux was listed as a secondary outcome. One secondary outcome is posted, while the registry record lists two outcome measures overall. The record does not explain the status of the other measure or provide its results in the information.

The registry record does not report a sample-size justification or a complete statistical analysis plan. Planning illustrations based on an observed effect are not evidence of the trial’s planned enrollment target or of the power actually achieved. No interim-analysis plan, prespecified stopping rule, or reason for the terminated status is 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

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 Patient-Reported Symptoms 7-Day Symptom Questionnaire (Heaviness, Achiness, Swelling, Throbbing & Itching) to Evaluate Improvement in Subject Reported Symptoms., measured over 12 weeks.

The primary endpoint concerns patient-reported heaviness, achiness, swelling, throbbing, and itching. It uses a subset of symptom questions associated with the VEINES-QOL and VEINES-Sym questionnaires. The registry description says the 7-Day Symptom Questionnaire combines responses across five symptoms. Each symptom response uses a four-point scale, with lower scores indicating better daily health outcomes. The daily total is the sum across the symptoms, with a possible range of 5 to 20.

A weekly average was calculated when at least four daily scores were present in the previous week. The endpoint compares the symptom score at post-treatment Week 12 with baseline. This patient-reported measure is intended to capture symptoms that affect daily experience, rather than only a clinical or imaging finding. The registry record also lists elimination of saphenous vein reflux as a secondary outcome, which concerns a different aspect of the condition.

The endpoint is described as continuous, with results summarized as means and standard deviations. A mean gives an average score for a group, while a standard deviation describes the spread of scores around that average. Because lower symptom scores represent better daily health outcomes, direction matters when reading the values. However, the registry record does not provide enough detail to establish how missing daily responses were handled beyond the stated weekly scoring rule, or how baseline and follow-up scores were combined in each reported analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous symptom score, so the reported group summaries use means and standard deviations. A mean is the arithmetic average of participant scores. A standard deviation describes variation around that average, but it is not the uncertainty of the mean itself. The registry reports the arm means and standard deviations alongside several inferential analyses. They answer different questions and should not be read as though they are all estimates of the same quantity.

What does a two-sided t-test assess?

A t-test compares means under assumptions about the data and the sampling process. A two-sided test evaluates evidence against equality in either direction, rather than testing only whether one group has a higher score. The registry reports a two-sided t-test for the two groups, with a mean difference in final values of -4.2, a 95% confidence interval from -6.2 to -2.3, and p < 0.001. The record does not report whether the test assumed equal variances or used another variant, so that detail should not be inferred.

The p-value describes how unusual data at least as incompatible with the null hypothesis would be if that hypothesis and the model assumptions held. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The confidence interval adds information about the uncertainty and range of estimates compatible with the analysis. A small p-value can coexist with questions about the analysis population, endpoint definition, missing observations, and prespecification.

Why are within-arm tests not group comparisons?

The registry reports a t-test within each treatment group. Those analyses assess change or difference within an arm as labeled in the registry; they do not directly compare the two randomized groups. To compare treatments, the relevant inferential analysis must estimate a between-group contrast. It is therefore not valid to infer that one treatment differs from another merely because a within-arm test is statistically notable in both groups, or because the p-values differ.

For the 1% group, the registry reports a mean difference in final values of -3.4, a 95% confidence interval from -5.8 to -1.0, and p = 0.011. For the 3% group, it reports -5.1, a 95% confidence interval from -8.7 to -1.6, and p = 0.010. The registry does not further describe the meaning of these within-arm differences, so their precise relationship to baseline scores should be read from the stated endpoint and analysis labels, not assumed from the numbers alone.

What does ANCOVA add?

ANCOVA is a model-based method for comparing group outcomes while adjusting for one or more covariates. In a clinical trial, adjustment may account for baseline measurements or other prespecified variables, but the covariates used in this study are not reported in the registry record. The registry gives an ANCOVA least-squares mean difference of -1.2, with a 95% confidence interval from -3.7 to 1.3 and p = 0.531. A least-squares mean is a model-based adjusted estimate, not necessarily the same quantity as a raw arm mean.

The interval spans zero. In general, when a confidence interval for a difference includes zero, the data are compatible with no difference as well as with differences in either direction across the interval, under the analysis assumptions. That does not prove the groups are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether uncertainty is contained within that margin; those details are not reported in the registry record.

How should the reported analyses be compared?

The two-group t-test and ANCOVA produce substantially different posted estimates and inferential results. The registry record does not explain their precise specifications, the endpoint data used for each, or which analysis was primary. The summary information is insufficient to reproduce either analysis. The difference between the estimates should therefore be treated as an interpretive limitation, rather than resolved by selecting whichever result appears more favorable or by constructing an unreported model.

In general, adjustment can change an estimate and its precision, especially when the adjusted covariates are related to the outcome. This is a general statistical explanation, not a claim about which covariates were used or why the results differ in this trial. The registry does not report enough detail to attribute the difference to adjustment, a change in analysis population, or another cause.

Why does dispersion matter?

In general, the standard deviation reflects how dispersed individual observations are around the group mean. Greater dispersion can make a mean less precisely estimated for a given amount of data. Small groups also tend to yield uncertain estimates, and a small number of observations can have substantial influence. The posted standard deviations describe observed variability, but do not reveal the distribution of scores or whether model assumptions were checked.

Over-dispersion is a general concern when observed variability exceeds what a model assumes. If that happens, standard errors and confidence intervals from a model that underestimates variability may be too optimistic. The registry record does not report an over-dispersion assessment, diagnostic checks, or any alternative variance method. No conclusion about whether over-dispersion occurred can be drawn from the arm summaries alone.

What do the planning illustrations mean?

Planning illustrations based on an observed effect use the observed effect as an input to show the sample size that would correspond to stated assumptions. The assumptions described for these illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set as a stated fraction of the observed effect. Such values are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions.

The registry record does not report the original sample-size justification, the intended effect size, or the reason for the enrollment target. A calculation based on the observed effect also inherits uncertainty from a small study and may give an unstable planning reference. It should not be interpreted as proof that the study had adequate power or that a nonsignificant result establishes no difference.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("ClariVein RES 1% Injection", "ClariVein RES 3% Injection")
n   <- c(10, 9)
m   <- c(7.2, 6.2)
sp  <- c(3, 1.87)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  ClariVein RES 1% Injection  10  7.200  3.000  5.054  9.346
CARM  ClariVein RES 3% Injection  9  6.200  1.870  4.763  7.637

11. Analyses Reported by the Sponsor

The registry reports the sponsor’s analyses as a two-sided t-test and an ANCOVA, along with separate within-group t-tests. The two-group t-test is labeled as a mean difference in final values of -4.2, with a 95% confidence interval from -6.2 to -2.3 and p < 0.001. The ANCOVA is labeled as a least-squares mean difference of -1.2, with a 95% confidence interval from -3.7 to 1.3 and p = 0.531. These results should be described as posted, with their stated methods and labels.

A separate unadjusted reconstruction of the two-arm comparison is not available from the posted summary statistics. Although arm means and standard deviations are listed, the comparison is marked as not estimable from those summaries. The registry record does not provide the individual-level data or analysis details needed to reconstruct the results. No new contrast should be calculated from the displayed arm summaries.

The registry record does not identify which analysis was prespecified as primary, explain the relationship between the t-test and ANCOVA estimates, or specify the ANCOVA covariates. Thus, the sponsor’s analyses are the available inferential results, but their differing estimates cannot be fully explained from the record. There is no recorded discrepancy flag indicating that a recalculation supersedes the sponsor’s result.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures overall and one posted secondary outcome, elimination of saphenous vein reflux. It also contains six analyses. The record information available for this analysis does not establish how the analyses map to all planned outcomes, whether all analyses were prespecified, or whether any were exploratory. The primary endpoint has multiple reported analyses, including a between-group t-test, within-group tests, and ANCOVA.

When multiple outcomes or analyses are examined, the chance of obtaining at least one apparently notable result can increase. Statistical methods can address this concern through prespecified testing hierarchies or adjustments, but the registry record does not report a multiplicity strategy. The posted p-values should therefore be read as results of their individual analyses, not as evidence that any multiplicity issue was controlled.

The primary score uses daily responses and a weekly average when at least four daily scores are present in the previous week. The registry describes this scoring rule, but missing-data handling beyond that rule is not reported in the registry record. It is not reported whether missing weekly scores were imputed, excluded, or addressed using another method. The number of participants with missing baseline or 12-week scores is also not reported.

The analysis population is not reported in the registry record. It is therefore unclear whether results use all randomized participants, participants with available endpoint data, or another population. The record also does not report adherence to assigned treatment or how deviations were handled. These details are relevant because exclusions or missing outcomes can affect both the group summaries and the estimated comparison.

The study status is terminated, but the reason for termination and any impact on follow-up or analysis are not reported in the registry record. A planned stopping rule, interim analyses, and any statistical adjustment associated with repeated interim looks are likewise not reported. No conclusions about these matters should be inferred from the termination status alone.

13. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 0 of 10 participants in the ClariVein RES 1% Injection group and 0 of 9 participants in the 3% group. It reports other adverse events for 1 of 10 participants in the 1% group and 3 of 9 participants in the 3% group. No deaths are reported in either group. The registry lists no top serious adverse-event terms.

These are counts among the participants recorded as at risk in each group. They are not a complete description of the nature, timing, duration, or severity of all events. The registry record does not report event-level details in the information, nor does it establish whether the other adverse events were considered related to the device or drug. No causal interpretation should be inferred from these counts.

With small groups, the absence of reported serious events does not establish that serious events cannot occur, and the difference in counts of other events does not by itself establish a treatment-related difference. The record information used for this analysis also does not specify the safety observation period or provide further details about how adverse events were collected. The figures are best read as the posted event counts, with those limits in mind.

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

The posted results describe symptom scores in two randomized groups receiving ClariVein RES with different STS concentrations. Arm means and standard deviations summarize the recorded scores, while the registry’s t-test and ANCOVA provide different model-based comparisons. The t-test reports a mean difference in final values of -4.2 with p < 0.001; the ANCOVA reports a least-squares mean difference of -1.2 with p = 0.531. The registry record does not explain why these estimates differ or identify which analysis was prespecified as primary.

These analyses do not establish that one concentration is superior. The confidence interval for the ANCOVA includes zero, while the t-test interval does not, and the two analyses are not interchangeable. The posted summaries cannot resolve the discrepancy between their results. A conclusion about comparative effects would require a clear account of the intended estimand, analysis model, covariates, and analysis population; those details are not fully reported in the registry record.

The endpoint is patient-reported and focuses on five symptoms over the prior week, with lower scores representing better daily health outcomes. It does not measure every aspect of venous insufficiency. The registry lists elimination of saphenous vein reflux as a secondary outcome, but the relevant result is not reported in the record information used. The symptom results therefore should not be taken as a substitute for evidence about that secondary measure.

The trial enrolled 19 participants and is recorded as terminated. The reason for termination, missing-data handling, and analysis population are not reported. This limits confidence in how well the available summaries represent the randomized groups. The reported p-values also do not indicate the probability that a treatment effect is real, its clinical importance, or the probability of benefit for an individual.

In general, statistical uncertainty is distinct from clinical importance. A confidence interval describes uncertainty in an estimate under a model; judging whether an effect matters clinically requires context and criteria that are not reported in the registry record. These results are a record of the posted analyses, not medical advice or a recommendation about treatment.

15. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should begin with the estimand and analysis method, not with a single p-value. The registry includes descriptive arm summaries, within-group tests, a two-group t-test, and an ANCOVA. The two group-comparison approaches report notably different estimates and uncertainty. Without a clear description of the prespecified primary analysis and model details, readers cannot determine from the registry record why the findings diverge.

It also illustrates the distinction between change within a group and difference between groups. Within-group tests address whether outcomes changed within each arm under their analysis, while a randomized comparison addresses whether the groups differ. The former does not establish the latter. This distinction is especially important when both groups have before-and-after measurements and several tests are reported.

The endpoint combines patient-reported symptoms into a continuous score. Its direction is clinically meaningful: lower values represent better daily health outcomes. Interpretation depends on understanding how daily responses form a weekly score, which participants contribute to the endpoint, and what contrast the analysis estimates. The registry provides part of that scoring description, but not all the missing-data and analysis-population details needed for a full appraisal.

The small enrollment and terminated status make transparent reporting particularly important. They do not establish that the results are invalid, but they make it important to know why the study stopped, who contributed data, and whether the planned analysis was completed. Those details are not reported in the registry record. The example shows how a technically significant result can coexist with unresolved questions about the analysis and its scope.

16. 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 identifies the study as terminated but does not report the reason. Without that information, the effect of termination on recruitment, follow-up, or analysis cannot be assessed. Enrollment was 19, with 10 participants assigned to the 1% arm and 9 to the 3% arm. The number with an observed 12-week score and the analysis population are not reported in the registry record.

The reported two-group t-test and ANCOVA yield different estimates and inferential results. The registry does not identify the prespecified primary model, describe the covariates in the ANCOVA, or explain the source of the difference. The test’s variance assumptions are also not reported. The posted arm means and standard deviations are not sufficient to reproduce the reported between-group comparison, which is recorded as not estimable from the available summaries.

The handling of missing endpoint data is not reported beyond the rule for calculating a weekly average when at least four daily scores are available. The registry does not state whether missing observations were excluded, imputed, or handled by another method. Nor does it report adherence, protocol deviations, or the masking procedures and personnel. These omissions limit assessment of possible bias and the reproducibility of the analyses.

The registry lists an outcome count of two, one posted secondary outcome, and six analyses, but does not report the multiplicity strategy or clearly map analyses to the planned testing hierarchy. The results for elimination of saphenous vein reflux are not reported in the record information used. The sample-size justification, interim-analysis plan, and stopping rule are also not reported in the registry record.

Finally, the safety information consists of event counts and does not include detailed event descriptions, attribution, or an observation period in the information. These limits constrain what can be concluded from both efficacy and safety results. They do not imply that unreported procedures or events did or did not occur.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Study Evaluating ClariVein With a Sclerosing Agent for the Treatment of Venous Insufficiency — NCT03311269.
• Registry record last updated 2022-03-02; status last verified 2022-02.
• Results first posted 2022-03-02.
• 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.

20. Record Summary

NCT03311269 is a Phase 2 randomized, parallel-group study of ClariVein RES with STS 1% or STS 3% for venous insufficiency associated with incompetent saphenous veins due to superficial venous reflux. The study is described as prospective, controlled, multicenter, and double blind. It enrolled 19 participants and is recorded as terminated.

The primary endpoint was change in a patient-reported five-symptom score at 12 weeks compared with baseline. The registry reports arm means and standard deviations, a two-sided t-test, within-arm t-tests, and an ANCOVA. The between-group t-test and ANCOVA estimates differ, and the registry does not report enough analysis detail to explain why. The reason for termination, analysis population, missing-data methods, and sample-size justification are not reported in the registry record.