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 Hydroxychloroquine for the First Thrombosis Prevention in Antiphospholipid Antibody Positive Patients (NCT01784523), a randomized phase 3 study. The primary outcome is Number of Participants With an Acute Thrombosis Event.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01784523 |
| Phase | Phase 3 |
| Condition | Antiphospholipid Syndrome |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hospital for Special Surgery, New York |
| Results posted | Yes |
2. Clinical Question
The study asks whether hydroxychloroquine, added to standard care, can prevent a first acute thrombosis event in patients who are persistently antiphospholipid antibody-positive but have not had thrombosis and do not have another systemic autoimmune disease. This is a primary-prevention question: the participants described in the registry record had no prior thrombosis, and the outcome is a new acute event.
Population
Persistently aPL-positive, thrombosis-free patients without other systemic autoimmune diseases.
Intervention
Hydroxychloroquine added to standard care, with a weight-adjusted dose described in the record.
Comparator
Standard treatment without hydroxychloroquine.
Primary question
Whether hydroxychloroquine is associated with fewer participants experiencing an acute thrombosis event.
The stated primary outcome counts participants with an acute thrombosis event. Its timeframe is listed as 2 years. The outcome description also refers to evaluation over the five year study period, so the record contains two different time references; it does not explain how they relate. The posted results list zero events in each arm. That is a description of the observed counts, not evidence that the two approaches have the same effect. With no events in either arm and no reported inferential comparison, the record does not establish the size or precision of any treatment difference.
3. Trial Design
The registry identifies this as a phase 3, randomized study with no masking. It describes a multi-center international study and names Hospital for Special Surgery, New York, as the sponsor. The listed start is 2013-02, primary completion is 2015-09-30, and the current status is terminated. The enrollment is 11 participants.
The posted outcome results are divided between standard treatment and hydroxychloroquine. Seven participants are listed in the standard-treatment arm, and four are listed in the hydroxychloroquine arm. The standard-treatment description says participants would not receive hydroxychloroquine. The intervention description says hydroxychloroquine would be added to standard care, using a weight-adjusted dose: 200 mg daily for those weighing less than 60kg and 400 mg daily (200 mg twice a day) for those weighing greater than 60kg.
There is a metadata inconsistency: the allocation is recorded as randomized, but the study model is listed as single group, while the outcome results show two arms. The record does not clarify this discrepancy. It also does not state why the study was terminated, how participants were assigned, whether treatment adherence was assessed, or how long each participant was followed. Those details are not reported in the registry record and should not be inferred from the arm labels or enrollment.
The registry lists one outcome measure and no posted analyses. The primary outcome is a participant count, with its timeframe recorded as 2 years. The outcome description separately refers to the five year study period. The registry record does not reconcile these timeframes. Consequently, the available result can be read as the reported arm-specific event counts, but not as a full account of the planned follow-up or analysis.
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 | Standard Treatment | Hydroxychloroquine |
|---|---|---|
| STARTED | 7 | 4 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 7 | 4 |
Reasons for not completing this period:
| Reason | Standard Treatment | Hydroxychloroquine |
|---|---|---|
| Study closed early | 7 | 4 |
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 | Standard Treatment | Hydroxychloroquine | Total |
|---|---|---|---|---|
| Participants analysed | 7 | 4 | 11 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 7 | 4 | 11 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 44 (SD 8.98) | 45.75 (SD 7.89) | 44.64 (SD 8.24) |
| Sex: Female, Male: Female | Participants | 7 | 3 | 10 |
| Sex: Female, Male: Male | Participants | 0 | 1 | 1 |
| Region of Enrollment: United States | Participants | 7 | 4 | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With an Acute Thrombosis Event, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with an acute thrombosis event. It is a binary outcome at the participant level: each participant either experienced at least one qualifying event during the defined period or did not. The record labels the unit as participants and gives the timeframe as 2 years. Its description also refers to a five year study period, and no clarification of this difference is reported in the registry record.
For a prevention study, counting participants who experience an event directly reflects the question of whether a first event occurs during follow-up. It is distinct from counting the total number of episodes, since a participant-level count does not describe repeat events. It is also different from a time-to-event outcome, which uses information about when an event occurs and how long participants are observed. The registry does not report event timing or person-time, so those quantities cannot be interpreted from the posted results.
The posted count is zero in the standard-treatment arm and zero in the hydroxychloroquine arm. These counts describe the observed outcomes for the listed participants. They do not by themselves estimate a reliable relative or absolute treatment effect. With no events in either group, a conventional two-arm comparison of event occurrence is not estimable from these data as posted. The record does not provide an effect estimate or confidence interval.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary-outcome results report zero participants with an acute thrombosis event in the standard-treatment arm and zero in the hydroxychloroquine arm. The respective arm sizes are 7 and 4. This is the central descriptive result: no participant in either listed group is reported to have experienced the endpoint within the reported results.
That pattern does not show that the treatments are equivalent, nor does it establish that hydroxychloroquine has no effect. A finding of no events in a small study can arise even when the underlying event risk is not zero. More importantly for a comparison, the observed counts contain no separation between arms. The registry flags that a two-arm comparison for this binary outcome is not estimable, and it lists no analysis. There is therefore no posted treatment-effect estimate, hypothesis-test result, or confidence interval to quantify the contrast.
In general, a confidence interval describes the range of effect values reasonably compatible with the observed data under the statistical model used. Its width reflects precision as well as the amount of information in the data. No confidence interval is reported in the registry record, so readers cannot use one to judge the range of plausible comparative effects. The zero counts alone do not replace that uncertainty assessment.
The enrollment of 11 and the arm sizes indicate that the result comes from a small number of participants. With no events, the information available for comparing event occurrence is especially limited. The record does not report a planned sample-size justification, a statistical analysis plan, an interim analysis, or a reason for termination. These absences prevent assessment of whether the final enrollment and observed follow-up matched the intended design.
The endpoint timeframe also deserves care. The registry gives 2 years for the primary outcome, while the endpoint description says the study aimed to assess prevention over the five year study period. The record does not say whether the posted counts cover one period, both periods, or a modified follow-up. Thus, the result should be interpreted as the registry's reported counts, without assuming a particular duration of observation for each participant.
Overall, the posted data document no primary events among the participants listed in either arm. They do not provide a precise estimate of comparative benefit or harm, and they cannot settle the clinical question. That distinction is important: absence of observed events in this small enrolled sample is a descriptive result, not proof of equal outcomes or proof that events cannot occur.
9. Statistical Methods Explained
The primary outcome is binary because it records whether each participant did or did not experience an acute thrombosis event during the outcome period. A common statistical approach for a two-arm binary outcome compares the proportion of participants with an event in each arm. Such a comparison needs information about the event and non-event counts in both groups. Here, the posted event count is zero in each arm, and the registry indicates that a two-arm comparison is not estimable. No treatment-effect estimate or analysis result is posted.
Why do zero events limit comparison?
When both groups have zero observed events, the data show no observed difference in event counts. But a numerical contrast intended to compare the event experience of the groups cannot be supported in the usual way when there are no events to distinguish them. The issue is not that zero is a meaningless observation: it accurately describes the posted counts. The issue is that zero events provide little information about how the underlying event probabilities compare. Many possible underlying risks can be compatible with observing no events in a small sample.
General statistical explanation: a confidence interval would communicate uncertainty around an estimated treatment contrast. It is not simply a measure of whether an observed result is statistically significant. In this case, the registry reports no interval, and its note says the binary two-arm comparison is not estimable. A confidence interval should not be inferred from the event counts alone.
What does the count measure?
A participant count records how many people experienced an event, not how many total event episodes occurred. The registry's outcome title and unit specify participants with an acute thrombosis event. The record does not report repeat events, event dates, or time-to-event analyses. A general distinction is useful: a participant-level binary analysis treats each person as event or no event within a defined window; a time-to-event analysis additionally uses the timing of an event and the duration of observation. The posted outcome is described as a count, not as a time-to-event measure.
The outcome timeframe is listed as 2 years, whereas the endpoint description refers to a five year study period. These descriptions do not establish a single unambiguous follow-up interval. Statistical interpretation depends on knowing the period during which event status was assessed, but the record does not clarify which period the posted arm counts represent.
What can planning calculations say?
General statistical explanation: sample-size calculations are planning tools. They describe the number of participants that would be needed under specified assumptions about the effect to detect, significance level, allocation, and statistical approximation. They are not a measure of the probability that a completed study has detected an effect, and they should not be described as observed power. The registry's planning assumptions specify a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect.
In this study, the observed event counts are zero in both arms, and the binary comparison is not estimable. The record does not report a usable observed effect for the planning illustration or a planning result. A sample-size requirement therefore cannot be interpreted from the posted data. The registry also does not report the study's own sample-size justification, so the planning assumptions should not be treated as the original design rationale.
Why does study structure matter?
The registry calls the allocation randomized and says the trial was not masked. Randomization is generally intended to make groups comparable at the point of assignment, on average, while masking is a way to limit the influence of knowledge about treatment on care or assessment. These are general methodological purposes, not evidence that either goal was achieved in this study. The record does not describe sequence generation, concealment of assignment, or outcome adjudication. In addition, it labels the model single group despite listing two treatment arms. That discrepancy leaves the design structure incompletely described.
No analyses are posted. The registry record does not report which statistical test or model was planned, whether any covariates were considered, or how incomplete follow-up would be handled. Because the outcome comparison is not estimable from the posted counts, there is no basis to reconstruct a sponsor analysis. The posted descriptive counts remain interpretable, but the inferential methods and their assumptions are not documented.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Standard Treatment | 7 | 0 | 0.0% | 0.0% to 41.0% | 0.0% to 35.4% | 0.3% to 36.9% |
| Hydroxychloroquine | 4 | 0 | 0.0% | 0.0% to 60.2% | 0.0% to 49.0% | 0.5% to 52.2% |
R code and output
arm <- c("Standard Treatment", "Hydroxychloroquine")
n <- c(7, 4)
events <- c(0, 0)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Standard Treatment 7 0 0.0 0.0 41.0 0.0 35.4 0.3 36.9
ARM Hydroxychloroquine 4 0 0.0 0.0 60.2 0.0 49.0 0.5 52.211. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and no secondary outcomes. It reports no analyses. With only one listed outcome measure, the record does not show a set of multiple posted outcome tests whose multiplicity adjustment can be assessed. However, the statistical analysis plan is not reported in the registry record, so it is not possible to determine whether additional outcomes or analyses were planned outside the posted results, or whether any multiplicity strategy was specified.
Missing-data handling is not reported in the registry record. There is no account of whether all enrolled participants completed follow-up, whether any outcome status was unknown, or how missing outcome information would have been treated. The posted arm counts should therefore be read as reported counts rather than as proof that outcome status was available for every enrolled participant throughout a common follow-up period.
The registry does not identify an analysis population, such as all randomized participants or participants who completed treatment. Although arm sizes and outcome counts are posted, the record does not explain the population rules used to produce them. It also does not report exclusions after randomization or deviations from assigned treatment. These details matter because different analysis populations can lead to different interpretations of a randomized comparison.
No interim analyses, stopping rules, or statistical monitoring procedures are reported in the registry record. The study status is terminated, but the reason for termination and its relationship to enrollment or analysis are not stated. Accordingly, no conclusions about planned monitoring, early stopping, missing outcomes, or analysis populations can be drawn from the record.
12. 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 |
|---|---|---|---|
| Standard Treatment | 0 | 7 | 0.0% |
| Hydroxychloroquine | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Standard Treatment | 0 of 7 |
| Hydroxychloroquine | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Standard Treatment | 0 of 7 |
| Hydroxychloroquine | 0 of 4 |
The registry's adverse-event results list zero participants with serious adverse events in the standard-treatment group, among 7 at risk, and zero in the hydroxychloroquine group, among 4 at risk. The listed counts for other adverse events are also zero in both groups, and deaths are listed as zero in both groups. No serious adverse-event terms are listed.
These figures describe the safety information posted in the registry; they do not establish that no adverse events occurred outside the recorded categories or observation period. The record does not describe the safety collection methods, event definitions, follow-up completeness, or the period used for these counts. It also does not explain whether the adverse-event results cover all enrolled participants or a defined analysis population.
General statistical explanation: rare or unobserved events are difficult to compare when the groups are small. Zero observed events do not prove that the underlying risk is zero, and the difference between zero counts cannot establish equal safety. The posted figures are therefore best read as reported counts, without a comparative safety estimate or a conclusion about future risk.
13. What the Result Does, and Does Not, Mean
The result establishes a limited descriptive fact: the registry reports no acute thrombosis events among the 7 participants listed in the standard-treatment arm and none among the 4 participants listed in the hydroxychloroquine arm. It also reports zero serious adverse events, other adverse events, and deaths in each arm. These are the recorded outcomes, not a complete estimate of what would happen in a larger population.
The result does not establish that hydroxychloroquine prevents a first thrombosis, that it has no effect, or that it is equivalent to standard treatment. No comparative analysis or effect estimate is posted, and the registry identifies the two-arm binary comparison as not estimable. The absence of events in both groups leaves no observed event contrast and does not provide a measure of precision.
It also does not establish the risk over a clearly defined common follow-up period. The primary outcome timeframe is listed as 2 years, while the endpoint description refers to the five year study period. The record does not reconcile those statements or provide individual follow-up durations. The reason the study was terminated is not reported in the registry record.
General statistical explanation: evidence about a treatment contrast depends both on the observed results and on how much information the study provides. A small number of participants with no events gives limited information about uncommon outcomes. More broadly, a result that is compatible with no observed difference is not automatically evidence that the underlying treatment effects are identical. A sufficiently precise estimate would be needed to make a strong claim about similarity, and no such estimate is posted.
The appropriate interpretation is therefore restrained. The registry documents zero observed events in both listed arms, but it does not answer the comparative efficacy question with a statistical estimate. It likewise does not provide enough information to make a firm comparative safety assessment. Conclusions beyond the reported counts would require information not reported in the registry record.
14. Why This Trial Matters Statistically
This trial is statistically instructive because its primary outcome is clinically direct but the posted event counts do not support a comparative estimate. A prevention study may be designed around an event that is uncommon in the enrolled population or during the observed period. When no events occur in either group, the result can be clear descriptively while remaining uninformative about the size of a treatment effect.
The study also illustrates why enrollment and allocation details matter. The registry lists 11 participants, with 7 in standard treatment and 4 in hydroxychloroquine. The small groups constrain the information available about event probabilities, especially when the outcome count is zero. The posted results cannot distinguish between treatments on the basis of observed events, and no inferential analysis is reported.
Record consistency matters as well. Randomized allocation is recorded, but the study model is labeled single group even though two arms are listed. The outcome timeframe is given as 2 years, while the outcome description refers to five years. These are not merely editorial details: clear design, analysis-population, and follow-up definitions help readers understand what was compared and over what period.
Finally, statistical significance and clinical interpretation are not substitutes for adequate information. No p-value or confidence interval is reported, and the comparison is not estimable from the posted binary counts. The record is a useful example of why zero events should not be mistaken for proof of no risk, no treatment effect, or equivalence. The limits of the information are part of the result's meaning.
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 principal limitation is the small enrollment: 11 participants are listed overall, with 7 in standard treatment and 4 in hydroxychloroquine. The primary outcome has zero events in both arms, and the registry says the two-arm binary comparison is not estimable. No treatment-effect estimate or confidence interval is posted, so the degree of uncertainty cannot be quantified from a reported comparative analysis.
The design description is internally inconsistent. Allocation is recorded as randomized, but the model is listed as single group, despite the two posted arms. The registry does not explain this difference. It also does not report the method of random sequence generation, allocation concealment, or masking of outcome assessment. The study is explicitly listed as having no masking, but the implications for outcome assessment are not described.
There is uncertainty about the outcome period: the primary outcome timeframe is 2 years, while its description refers to the five year study period. Individual follow-up times and the period covered by the posted counts are not reported. The study is terminated, but the reason is not stated. The record also does not report a sample-size justification, analysis plan, analysis population, handling of missing data, or interim procedures. No secondary outcomes or analyses are posted.
These record-specific limitations mean that the arm counts can be described, but the intended comparison and its precision cannot be fully assessed. The absent details should not be filled in by assumptions about the protocol or reasons for termination.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Hydroxychloroquine for the First Thrombosis Prevention in Antiphospholipid Antibody Positive Patients — NCT01784523.
- Registry record last updated 2021-09-14; status last verified 2021-08.
- Results first posted 2021-05-04.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry describes a phase 3, randomized, unmasked study of hydroxychloroquine for primary thrombosis prevention in persistently aPL-positive, thrombosis-free patients without other systemic autoimmune diseases. It reports enrollment of 11 and lists 7 participants in standard treatment and 4 in hydroxychloroquine. The study status is terminated.
The primary outcome is the number of participants with an acute thrombosis event. Its timeframe is listed as 2 years, while the outcome description refers to five years. The posted event count is zero in each arm. The registry lists no analyses and indicates that a two-arm comparison for the binary outcome is not estimable. It also reports zero serious adverse events, other adverse events, and deaths in both arms.
The record does not report a comparative effect estimate, confidence interval, reason for termination, or clarification of the design and timeframe discrepancies. The posted results therefore support a description of the recorded counts, but not a precise conclusion about comparative efficacy or safety.