A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome (NCT00537290), a na phase 2 study. The primary outcome is Number of Participants Experiencing Serious and Non Serious Adverse Events.

2. Clinical Question

This question is descriptive: it concerns the number of participants with reported adverse events in the rituximab group. With no control group, the safety counts do not establish how event experience would compare under another treatment or without rituximab. The registry record gives separate counts for participants affected by serious and other adverse events, along with a death count. Those categories should be read separately; the record does not describe overlap between them or provide a combined count that can be interpreted as the number experiencing any event.

The follow-up period is stated as 52 weeks, with an additional 4 months if needed for patients with low B cell counts. The record does not give participant-level follow-up or explain how many required the additional period. Consequently, the central question is what adverse events were recorded during the specified observation period, not whether rituximab caused them or whether it changed risk relative to a comparator.

3. Trial Design

RITAPS, registered as NCT00537290, is a completed phase 2 study sponsored by Hospital for Special Surgery, New York. The registry describes it as a single-group study with no masking. Allocation is recorded as NA, and no like-for-like control group is listed. The enrollment recorded for the study is 19.

All participants in the described arm received rituximab. The arm description specifies 1000 milligrams by intravenous infusion on Days 1 and 15. The study title frames the target as anticoagulation-resistant manifestations of antiphospholipid syndrome, while the registry condition is Antiphospholipid Syndrome. Further eligibility criteria and details about the clinical manifestations under study are not reported in the registry record.

The primary outcome is the number of participants experiencing serious and non-serious adverse events. Events were evaluated throughout 52 weeks, with an additional 4 months if needed for patients with low B cell counts. The record lists “The Efficacy of Rituximab” as a secondary outcome, but does not report its result in the available outcome information.

The study start is recorded as 2007-09, and primary completion as 2013-01. The status is completed. These dates identify the registry timeline, but do not indicate when each participant was enrolled or how long each person was followed. Because the design has one treatment group and no masking, the findings are descriptive and are not a randomized comparison. Details of a protocol-defined statistical analysis plan, sample-size justification, interim analyses, and allocation procedures are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Laboratory criteria defined as positive results of a LAC test, positive aCL IgG/IgM/IgA isotype (≥40), and/or positive anti-β2GPI IgG/IgM/IgA isotype (≥40) on 2 or more occasions, at least 12 weeks apart. Clinical criteria defined as 1)persistent thrombocytopenia 2)Cardiovascular disease 3)skin ulcer 4)aPL nephropathy 5) cognitive dysfunction.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients enrolled in the 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.

Population: Patients included in the study

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Experiencing Serious and Non Serious Adverse Events, measured over 52 weeks + additional 4 months if needed.

The primary endpoint counts participants who experienced serious and non-serious adverse events during follow-up. Its title refers to participants rather than the total number of event episodes, so the reported measure concerns people affected, not how many times events occurred. The registry description says that adverse events were evaluated throughout 52 weeks, with an additional 4 months if needed for patients with low B cell counts.

Recording safety events is a way to characterize what occurred while participants were receiving study treatment and being followed. It can identify events that warrant detailed clinical description and provide a safety profile for the group studied. The record lists separate affected-participant counts for serious and other adverse events, as well as deaths. It does not give a combined count or explain whether participants appear in both event categories.

As a general statistical point, participant counts are often easier to interpret than episode counts when the question is how many people were affected. However, counts alone do not show the timing, duration, recurrence, or severity of every event. The endpoint is not a comparison with an untreated or alternative-treatment group, and it cannot by itself determine whether an event was caused by rituximab. Definitions of seriousness and event attribution are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a phase 2, single-group study with no masking. The recorded allocation is NA. These design features matter because the reported safety results are counts within a treated group rather than estimates from a randomized comparison. A single-group study can describe observations in participants who received the intervention, but it does not directly estimate how outcomes differ from a control group. Lack of masking means treatment knowledge was not concealed, although the record does not describe how that feature affected event ascertainment.

What does a participant count represent?

The primary endpoint is framed as the number of participants experiencing serious and non-serious adverse events. This is different from counting every event episode. If one participant experiences repeated events, a participant-based measure concerns whether that participant was affected, rather than the number of episodes. The registry reports separate affected-participant counts for serious events and other adverse events. It does not report the amount of overlap between these groups, so they cannot be added to infer a unique total with any event.

The group’s risk denominators are listed as 19 for the serious-event and other-event summaries. A denominator indicates the group at risk for that reported category, but does not show the follow-up actually completed by every participant. The registry specifies observation through 52 weeks, with an additional 4 months if needed for patients with low B cell counts. Participant-level follow-up and the number who required the additional period are not reported in the registry record. This limits assessment of whether everyone contributed the same observation time.

Why does the design limit comparisons?

In a randomized comparison, assignment to different groups can support estimation of a treatment contrast, subject to design and analysis assumptions. This study is recorded as single-group, so there is no separate trial control arm for such a contrast. The counts can describe events recorded in the rituximab group, but they cannot isolate the effect of rituximab from other explanations. The record also gives no adjusted analysis or comparative estimate.

As a general concept, confounding occurs when differences in participant characteristics or care are related to both the treatment received and the outcome. With no comparison group, the registry results cannot account for these alternative explanations through a treatment contrast. This is not a judgment about whether individual events were related to treatment; the record’s listed counts alone do not establish that relationship.

What analyses are reported?

The registry lists two outcome measures and zero analyses. It names “The Efficacy of Rituximab” as a secondary outcome but does not provide an efficacy result in the outcome information. No statistical testing method, confidence interval, adjusted estimate, or analysis population definition is reported in the registry record. The protocol’s statistical plan, any interim analyses, and the rationale for the enrollment target are also not reported.

In general, a confidence interval provides a range of estimates compatible with data and a specified statistical procedure; it is useful for understanding precision as well as the direction and magnitude of an estimate. Since the record gives no interval or inferential analysis for the reported safety counts, precision cannot be assessed from a reported interval. A count should not be treated as a precise estimate of risk beyond the participants observed.

How should the planning illustration be read?

The sample-size assumptions describe a planning illustration based on an observed effect, not the study’s original design or an observed-power calculation. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its target effect is a stated fraction of the observed effect. Those assumptions differ from the recorded single-group design. They describe hypothetical planning for a two-arm study rather than a feature of RITAPS.

As a general concept, a planning sample size asks how many participants might be needed under specified assumptions to detect a chosen effect with a chosen statistical procedure. It does not show that a completed study had a particular probability of finding an effect, and it does not establish that the chosen assumptions are clinically or scientifically appropriate. The record does not report that this illustration governed enrollment. Its values should be interpreted only as planning scenarios, not as observed trial results or evidence of efficacy.

For outcomes based on event counts, the choice of statistical model depends on how events arise and how variability relates to the mean. As a general explanation, over-dispersion means the observed variability is greater than a simple model assumes; ignoring it can make uncertainty appear smaller than it is. No event-count model or over-dispersion assessment is reported in the registry record. The primary endpoint is participant-based, and the record does not supply event episodes or model-based estimates from which to assess that issue.

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("Rituximab")
n      <- c(19)
events <- c(19)
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  Rituximab  19  19  100.0  82.4  100.0  83.2  100.0  83.2  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and zero analyses. One named secondary outcome is “The Efficacy of Rituximab”; the primary outcome concerns participants with serious and non-serious adverse events. The efficacy outcome’s detailed definition, results, and analysis are not reported in the registry record. There is no reported testing hierarchy or multiplicity adjustment.

As a general statistical concept, multiplicity arises when several outcomes or comparisons are examined: the more questions tested, the greater the opportunity for chance findings if each is interpreted independently. A prespecified analysis plan can clarify which outcome is primary and how secondary results should be interpreted. The registry record does not report a statistical plan, so it is not possible to determine whether any multiplicity strategy was planned or applied.

Missing-data handling is not reported in the registry record. The record gives the group at risk for the safety summaries and a follow-up timeframe, but not participant-level completion, reasons for missing observations, or imputation procedures. The analysis population is also not described beyond the primary outcome’s statement that it covers all patients enrolled in the study. It is therefore not possible to assess whether all enrolled participants contributed complete follow-up or how incomplete observation was handled.

These gaps do not change the recorded counts, but they constrain interpretation. In particular, the available information does not establish whether outcome ascertainment was complete for every participant or whether the efficacy outcome was analyzed according to a prespecified approach.

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: pneumonia (10.5%), antiepileptic drug adjustment (history of seizure disorder) (5.3%), brain surgery (history of seizure disorder) (5.3%), subdural hematoma (5.3%), new-onset focal motor seizure due to previous stroke (5.3%).

The registry reports serious adverse events affecting 12 participants among 19 at risk, and other adverse events affecting 17 participants among 19 at risk. It reports 0 deaths. These are participant counts for the rituximab group. The record does not state how many people were in both event categories, so the serious and other-event counts cannot be added to obtain a total number affected.

The listed serious-event terms include Pneumonia at 10.5%. Antiepileptic drug adjustment (history of seizure disorder), Brain surgery (history of seizure disorder), Subdural hematoma, New-onset focal motor seizure due to previous stroke, and 48-hour EEG monitoring and new-onset partial sensory seizure are each listed at 5.3%. The entries should be read as registry-reported safety terms and percentages, not as estimates comparing treatment with another option.

As a general point, the presence of an event during a study does not establish that treatment caused it. The registry record does not report event attribution, timing, recurrence, or detailed criteria for seriousness. The counts also do not convey whether participants had equal follow-up, beyond the stated period of 52 weeks and the possibility of an additional 4 months for patients with low B cell counts. They describe the recorded safety experience, with these interpretive limits.

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

The results describe adverse events recorded in a single group of participants receiving rituximab. The record reports 12 participants affected by serious adverse events and 17 affected by other adverse events, with 0 deaths. It also lists several serious-event terms and their registry percentages. These observations characterize the safety experience reported for the group during the stated follow-up.

They do not show whether rituximab increases or decreases the frequency of adverse events compared with another treatment, because the registry describes no comparator group. Nor do the counts establish whether a particular event was caused by rituximab. The record does not provide comparative estimates, causal analyses, or event-attribution details. The difference between the serious-event and other-event counts should not be interpreted as a contrast between mutually exclusive groups, since overlap is not reported.

The study title and secondary outcome identify efficacy as an area of interest, but the registry outcome information does not report an efficacy result. Consequently, the safety findings cannot establish whether clinical manifestations changed during treatment or whether any change would be attributable to the intervention. The registry also does not report confidence intervals or hypothesis tests for these results, so statistical precision cannot be assessed using inferential measures from the record.

As a general statistical principle, descriptive results are most informative when interpreted in light of design, follow-up, measurement definitions, and uncertainty. Here, the single-group design supports description of recorded events, while leaving treatment comparisons unresolved. The reported counts are evidence about what was recorded among enrolled participants, not a stand-alone conclusion about treatment benefit, harm relative to alternatives, or causation.

14. Why This Trial Matters Statistically

This trial illustrates why the design behind a clinical result matters as much as the count itself. Safety events were reported for a single rituximab group, so the results describe that group’s experience rather than a contrast with a control. Readers can identify which event counts the registry records, but cannot use them to estimate how outcomes would differ under another treatment or no treatment.

It also highlights the distinction between participants affected and event episodes. The primary endpoint is worded as a count of participants, and the registry reports affected-participant counts. Without overlap information, separately reported categories should not be combined. This distinction is important whenever one person could contribute to more than one category or experience repeated events.

The record names efficacy as a secondary outcome but provides no efficacy result in the reported outcome information. It lists zero analyses, and details of an analysis plan, missing-data handling, and multiplicity approach are not reported. Those absences limit assessment of how outcomes were selected, analyzed, or interpreted. The planning assumptions for a hypothetical two-arm sample-size illustration also differ from the recorded single-group design, underscoring that planning scenarios are not trial findings.

As a general lesson, statistical conclusions depend on design and reporting as well as numerical summaries. Counts can be useful descriptions, yet without a comparison group and stated uncertainty they do not answer causal or comparative questions. Clear distinction between observed safety information, missing efficacy results, and hypothetical planning assumptions helps prevent a descriptive record from being read as stronger evidence than it supports.

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 main design limitation is that the registry describes a single group with no like-for-like control comparison. The safety counts therefore cannot estimate a treatment contrast or separate treatment effects from other explanations. The record also reports no masking, so the potential influence of treatment knowledge on event reporting or assessment cannot be evaluated from the available details.

The enrollment recorded is 19, and the outcome information provides participant counts without confidence intervals or reported statistical analyses. The registry does not report the protocol’s statistical analysis plan, sample-size justification, interim analyses, or the method used to assess uncertainty. No efficacy result is reported for the named secondary outcome.

Follow-up is stated as 52 weeks, with an additional 4 months if needed for patients with low B cell counts. The record does not report participant-level follow-up, how many needed additional observation, or how missing data were handled. Event attribution, detailed seriousness criteria, recurrence, and timing are also not reported in the registry record. The relationship between participants with serious and other adverse events is not specified, preventing interpretation of a combined affected-participant total.

Finally, further eligibility and clinical characterization details are not present in the outcome description. This limits understanding of how broadly the findings may apply beyond the enrolled group. These reporting and design limitations do not negate the recorded counts; they define the narrower descriptive questions those counts can answer.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome — NCT00537290.
• Registry record last updated 2017-10-31; status last verified 2017-10.
• Results first posted 2017-10-31.
• 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

NCT00537290 is a completed phase 2, single-group study of rituximab in antiphospholipid syndrome, sponsored by Hospital for Special Surgery, New York. The study start is recorded as 2007-09, primary completion as 2013-01, and enrollment as 19. The intervention description specifies intravenous rituximab on Days 1 and 15.

The primary outcome counts participants with serious and non-serious adverse events over 52 weeks, with an additional 4 months if needed for patients with low B cell counts. The safety results report 12 participants affected by serious events, 17 by other events, and 0 deaths. The record also lists “The Efficacy of Rituximab” as a secondary outcome but does not report its result in the outcome information.

No comparator group or statistical analyses are reported. The safety counts are descriptive observations, not a randomized comparison or evidence of causation. Analysis-plan details, missing-data handling, and efficacy results are not reported in the registry record.