Low-Dose Alteplase to Treat Blood Clots in Deep Leg Veins: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low-Dose Alteplase to Treat Blood Clots in Deep Leg Veins (NCT00082355), a na phase 2 study. The primary outcome is Number of Participants With Restored Venous Function.

2. Clinical Question

The clinical rationale in the registry description is that anticoagulants can prevent clots from enlarging or moving to the lung but do not reliably dissolve clots in the leg. The study’s stated aim was to evaluate lower-dose rtPA for clot dissolution and assess whether this approach could have fewer bleeding complications than higher-dose regimens. That aim describes the question motivating the study; it is not evidence that the treatment achieved either outcome.

3. Trial Design

This was a phase 2, completed, single-group study with enrollment of 30. Allocation is marked not applicable, and the study had no masking. With no concurrent comparison group, its design can describe outcomes among participants treated with alteplase, but it cannot directly estimate how those outcomes differ from a separate control group.

The record describes treatment for acute deep vein thrombosis in the lower extremities, including clots in the pelvis or leg. Eligibility described in the study summary included age 18 years or older, symptoms for 14 days or less, and no history of deep-vein clots. Participants were admitted to hospital for up to 5 days. The procedure included venography to identify clot location and insertion of a catheter into a vein, followed by intraclot alteplase. The arm description specifies up to 4 low-dose treatments, with less than 10 mg/day.

The study start is recorded as 2004-05, primary completion as 2010-03, and status as completed. The record’s arm description says the intention was to evaluate treatment safety, efficacy, and durability over 6 months in 25 patients. The primary-outcome description also says the initial goal was evaluation in 25 patients, while 30 were treated. It notes that two participants did not complete the study before being assessed for a further detail, but that sentence is incomplete in the registry record. The exact handling of those participants is not reported in the registry record.

Because the design is single-group and unmasked, changes after treatment cannot be separated from changes that might have occurred for other reasons or from the way outcomes were assessed. The record does not report a protocol-level statistical plan, the rationale for the target enrollment, or details of any comparison with historical outcomes.

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: 2 patients who were incorrectly diagnosed with Deep Vein Thrombosis (DVT) were excluded from the protocol after a preliminary ultrasound exam at NIH indicated they did not have DVT.

Initial Results of Thrombolytic Therapy

Reasons for not completing this period:

5 Year Recurrent Thromboembolism Rate

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number of participants analyzed is an Intent-to-Treat (ITT) population. The initial goal was to be able to evaluate outcomes of treatment of DVT with alteplase over a 6 month period in 25 patients. 30 patients were treated but two participants did not complete the study before being assessed for this outcome measure.

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 Number of Participants With Restored Venous Function, measured over 6 months.

The primary endpoint is the number of participants with restored venous function at 6 months. The record describes venous function as blood flow through affected areas and uses patency as another term for restored flow. Venography and ultrasound exams are named as the assessment methods.

This endpoint is relevant to the study’s stated purpose because the intervention was intended to lyse clots, and restored flow is a measure of whether the affected vein is open. The registry description says the endpoint concerns acute and subacute deep venous thrombosis of the lower extremities and/or pelvis. It is a participant count, rather than a continuous measurement of the degree of blood flow.

Interpretation depends on knowing how many participants met the definition of restored venous function, how many were assessed, and how participants without an assessment were handled. The registry record names an intent-to-treat population and notes that 30 participants were treated, but its description of participant completion is truncated. The primary endpoint result itself is not reported in the registry record. The number with restored venous function, any accompanying uncertainty estimate, and the detailed criteria used to classify patency are therefore not available in the record.

In general, imaging-based measures can provide an objective assessment of whether a vein is open, but reliability also depends on clear definitions and consistent assessment. The record identifies the imaging methods but does not report further details about reading procedures or reproducibility.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the design allow?

The registry identifies a single-group study with no masking and no randomized allocation. In general, a single-group design follows participants who receive an intervention without a separate concurrent control group. It can describe outcomes in that treated group, but it does not directly estimate a treatment contrast between groups. Any observed change may reflect the intervention, the natural course of the condition, other care, or measurement and follow-up processes. Without a comparator, those explanations cannot be distinguished reliably by a direct between-group comparison.

Masking is a method intended to limit the influence of knowledge about treatment assignment on care or outcome assessment. The record says there was no masking. It does not report whether imaging assessments were independently reviewed or whether any safeguards were used to reduce assessment bias. Those details are not reported in the registry record.

What does a participant count convey?

The primary endpoint is a count of participants classified as having restored venous function at 6 months. A count is straightforward to understand, but it needs context: the number assessed, the rule for classifying restored function, and how missing assessments were handled. A count alone does not describe uncertainty or permit a comparison with another treatment. The registry record does not report the endpoint count or its analysis.

In general, a confidence interval expresses the range of values compatible with the observed data under the method used. Its width reflects statistical precision: a wider interval indicates less precision, while a narrower interval indicates more. No confidence interval for the primary outcome is reported in the registry record, so the precision of the estimated outcome cannot be evaluated.

Why does the analysis population matter?

The primary-outcome description identifies an intent-to-treat population and says 30 participants were treated, while also noting an initial goal of evaluating 25 patients. In general, intent-to-treat analysis refers to analyzing participants according to their assigned group, regardless of whether they completed or adhered fully to treatment. That principle is most directly applied in randomized trials, where assignment defines the group. This study is recorded as single-group, and the registry’s description of participants who did not complete the study is incomplete. The exact analysis population and the treatment of incomplete outcomes are not reported in the registry record.

Missing outcome data can affect results if participants without an assessment differ in their outcomes from those with an assessment. In general, statistical methods may make assumptions about missing outcomes, but no such method or assumption is reported in the registry record. The available description does not establish whether the primary analysis included every treated participant or only participants with an available assessment.

How should planning illustrations be read?

General sample-size calculations use assumptions about the outcome, the effect a study aims to detect, the significance level, power, and the allocation between groups. The planning illustration associated with this study is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is based on a fraction of the observed effect. These are planning assumptions, not results from the trial.

The design recorded for this study is single-group, not a two-arm comparison. Thus, the stated equal-allocation assumption does not describe the enrolled trial design. Planning figures that use those assumptions should not be interpreted as the sample size actually needed for this single-group study. A sample-size calculation is also not observed power: it does not report the probability that the completed study detected an effect. No observed power estimate is reported in the registry record.

General power calculations depend on the effect size used as an input. When an observed effect is used to construct a planning illustration, the resulting scenarios show what enrollment might be needed under those assumptions; they do not validate the observed effect or establish that a future study would reproduce it. The actual planning values and detailed statistical plan are not reported in the registry record.

What is not available for statistical review?

The registry record lists two outcome measures and no analyses. It does not report a primary endpoint estimate, uncertainty interval, p-value, covariate-adjusted model, or statistical test. It also does not describe an interim analysis, a formal analysis plan, or adjustments for multiple testing. Those items are not reported in the registry record and should not be inferred from the endpoint descriptions or the planning assumptions.

In general, over-dispersion occurs when variation in count data is greater than a model assumes; ignoring it can make uncertainty appear too small. This concept is not a reported feature of this study’s analysis. The primary outcome is recorded as a participant count, and no model is described, so the registry record does not establish whether over-dispersion was relevant or assessed.

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("Alteplase")
n      <- c(30)
events <- c(28)
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  Alteplase  30  28  93.3  77.9  99.2  78.7  98.2  78.6  98.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint, the number of participants with restored venous function, and a secondary outcome concerning the number of participants who developed hemorrhage. It does not report a statistical plan explaining how these outcomes were to be analyzed together, whether any additional outcomes were considered, or whether adjustments for multiple testing were planned. The handling of multiplicity is not reported in the registry record.

In general, testing several outcomes can increase the chance of finding an apparently notable result by chance. A prespecified hierarchy or adjustment can help control that risk, but the record does not say whether either approach was used. There are no reported analyses or outcome estimates to assess for multiplicity in the information available.

The primary outcome description names an intent-to-treat population and states that 30 participants were treated, alongside an initial goal of evaluating 25 patients. It also begins to describe two participants who did not complete the study before the sentence ends. The record does not report the exact analysis population, the number assessed for the primary endpoint, or how missing assessments were treated. It does not say whether any imputation or sensitivity analysis was performed.

In general, incomplete follow-up can affect interpretation when the likelihood of missingness is related to participants’ outcomes. The record does not provide enough information to evaluate that possibility. The planned 6-month assessment is stated, but outcome completion and missing-data handling are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry adverse-event summary records 0 serious adverse events among 30 at risk and 2 other adverse events among 30 at risk in the alteplase group. These are event-summary counts, not evidence that the intervention caused or prevented events. The registry record does not provide event descriptions for the two other adverse events, their timing, or an assessment of their relationship to treatment.

Hemorrhage is named as a secondary outcome, but its result is not reported in the registry record. No serious-event terms are listed in the available summary. The absence of listed terms should not be taken to mean that all possible event details or clinical context are available.

In general, a count of zero serious events in a study group does not prove that an intervention has no serious risks. A small study may provide limited information about uncommon events, and safety interpretation also depends on event definitions, observation time, completeness of reporting, and comparison with an appropriate control group. The registry describes hospital admission for up to 5 days and a 6-month outcome horizon, but it does not state a separate safety follow-up period or provide enough detail to determine the completeness of adverse-event ascertainment.

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

The registry record describes a phase 2 study intended to assess low-dose alteplase for acute deep vein thrombosis, with restored venous function at 6 months as the primary endpoint. It also records a safety aim and lists hemorrhage as a secondary outcome. However, the primary endpoint count and hemorrhage result are not reported in the registry record. The available information therefore does not establish what proportion of participants had restored venous function or how often hemorrhage occurred.

The study was single-group and unmasked. In general, that design can describe outcomes after treatment, but it cannot make a direct comparison against another treatment or establish what would have happened in the absence of the intervention. The registry record also does not provide a statistical analysis, confidence interval, or p-value for the primary endpoint. The precision of an efficacy estimate cannot be assessed.

The safety summary reports 0 serious adverse events among 30 at risk and 2 other adverse events among 30 at risk. Those counts are useful as a description of what the registry summary records, but they do not determine whether the treatment caused events or provide a comparative assessment of safety. The record does not include event narratives or the result for its listed hemorrhage outcome.

The study’s stated rationale and aims should be kept separate from reported findings. The record says the study was designed to evaluate clot dissolution and durability, and to consider bleeding complications relative to higher-dose regimens. It does not report results that answer those comparisons. It is therefore not possible to conclude from this record that alteplase did or did not restore venous function, or that it did or did not reduce bleeding complications.

14. Why This Trial Matters Statistically

This study raises statistical issues that are especially visible in a small, single-group clinical study. The primary endpoint is clinically interpretable as a participant count with restored venous function, but a count needs a clear denominator, a reproducible endpoint definition, and a transparent account of missing assessments. The registry record identifies the assessment methods and an intent-to-treat population, yet it does not report the endpoint count or fully describe participant completion.

The single-group design also makes the distinction between observed outcome and treatment effect important. A treated-group outcome can be reported descriptively, but attribution requires a suitable comparison. Without one, differences over time cannot be isolated from natural change or other influences. The absence of masking is another consideration because outcome assessment may be influenced by knowledge of treatment, although the record does not report whether safeguards were used.

Safety counts require similar care. A zero count for serious adverse events is a descriptive finding in the registry summary, not proof that serious harms cannot occur. The listed hemorrhage endpoint has no reported result, and the event details for other adverse events are absent. Transparent reporting of definitions, follow-up, and denominators is essential for interpreting safety information.

Finally, planning calculations should be distinguished from trial findings. The associated assumptions describe a two-arm, equal-allocation illustration even though the recorded trial is single-group. Any sample-size scenario based on a fraction of an observed effect is a planning exercise, not observed power and not evidence that a treatment effect was established. These distinctions help keep design, analysis, and clinical interpretation aligned with what the record actually reports.

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 central limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. There is no count of participants with restored venous function at 6 months, and no uncertainty estimate or statistical analysis is included. The record therefore does not permit assessment of the magnitude or precision of the primary outcome.

The single-group design has no concurrent control, and the study was unmasked. These features limit causal interpretation and leave open the possibility that outcome measurement or changes over time were influenced by factors other than treatment. The record does not report whether imaging was assessed using independent or masked review.

Participant accounting is also incomplete. The record states that 30 participants were treated, gives an initial goal of 25 patients, and begins a statement that two participants did not complete the study before an assessment. The sentence is truncated, so the reason for noncompletion, the endpoint denominator, and the handling of missing data are not reported in the registry record.

Safety interpretation is constrained by the lack of event detail. The adverse-event summary provides counts but no descriptions or treatment-attribution assessments, and the hemorrhage outcome has no reported result. The registry record does not report a detailed statistical plan, outcome analysis, multiplicity approach, or the rationale for the planned enrollment. These gaps limit both clinical interpretation and independent statistical review.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Low-Dose Alteplase to Treat Blood Clots in Deep Leg Veins — NCT00082355.
• Registry record last updated 2014-11-06; status last verified 2014-10.
• Results first posted 2012-12-19.
• 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

The registry record describes a completed phase 2, single-group study of low-dose alteplase for acute deep venous thrombosis of the lower extremity. It records enrollment of 30, no masking, and no randomized allocation. The study began in 2004-05 and reached primary completion in 2010-03.

The primary endpoint was the number of participants with restored venous function at 6 months, assessed by venography and ultrasound. The record describes up to 4 intraclot alteplase treatments at less than 10 mg/day. It states that 30 participants were treated, while the initial goal was evaluation in 25 patients; the account of study completion is incomplete.

The available adverse-event summary records 0 serious adverse events among 30 at risk and 2 other adverse events among 30 at risk. The primary outcome result, hemorrhage result, and statistical analysis are not reported in the registry record.