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 and Phlebotomy for Treating Porphyria Cutanea Tarda (NCT01573754), a randomized phase 2 study. The primary outcome is Remission.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01573754 |
| Phase | Phase 2 |
| Condition | Porphyria Cutanea Tarda |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 48 |
| Arms in the primary outcome | 2 |
| Lead sponsor | The University of Texas Medical Branch, Galveston |
| Results posted | Yes |
2. Clinical Question
The registry record describes a prospective comparison of low-dose hydroxychloroquine and phlebotomy for porphyria cutanea tarda. Its stated hypothesis is that hydroxychloroquine is noninferior to phlebotomy in time to remission. The posted primary outcome is remission time, defined by a decrease in plasma porphyrin concentration to less than 0.9 mcg/dL. The record also describes remission as achieving a normal plasma porphyrin concentration.
Population
People with well-documented porphyria cutanea tarda who met specific criteria for randomization. The registry lists enrollment of 48. The criteria themselves and further details of the enrolled population are not reported in the registry record.
Intervention
Low-dose hydroxychloroquine, 100 mg by mouth twice weekly. The registry describes this as a drug intervention.
Comparator
Phlebotomy, 450 mL biweekly. The registry describes this as a procedure intervention.
Primary question
How does time to remission compare between the randomized treatment groups, and are the posted results compatible with the stated noninferiority hypothesis? The registry reports group medians and full ranges, but does not report a noninferiority margin or an inferential comparison.
The clinical question concerns the time until a laboratory-defined remission threshold is reached, rather than a direct comparison of symptom change. The registry lists secondary outcomes involving plasma porphyrin reductions and days with normal urinary porphyrin levels. Those outcomes provide additional laboratory and time-based measures, but their results are not included in the posted outcome information.
3. Trial Design
This is a randomized, parallel-group phase 2 trial. Participants meeting specific criteria were assigned to hydroxychloroquine or phlebotomy by randomization, according to the registry summary. The record describes no masking. It lists the study as completed, with enrollment of 48. The sponsor is The University of Texas Medical Branch, Galveston.
The two interventions were low-dose hydroxychloroquine 100 mg by mouth twice weekly and phlebotomy 450 mL biweekly. The parallel design means the treatment groups received their respective interventions rather than crossing between them as part of the described comparison. Random allocation is intended, in general, to reduce systematic differences between groups at assignment; it does not guarantee that all group characteristics will be identical, particularly in a trial of this size.
The registry lists the start date as 2006-03-21 and the primary completion date as 2021-07-06. The primary outcome timeframe is described as follow-up to the end of the study, an average of 3 years. The summary says patients were followed until remission. Further details about visit schedules, treatment stopping rules, deviations from assigned treatment, or the timing and conduct of follow-up are not reported in the registry record.
The posted primary result is a median time to remission for each treatment group, accompanied by a full range. This design and outcome are consistent with a time-to-event question: the event is reaching the specified remission threshold, and the measured quantity is the elapsed time until that event. However, the registry result does not include a reported hazard ratio or another inferential estimate comparing the groups. No protocol-level sample-size justification, interim analysis plan, or detailed statistical analysis plan 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.
Before assignment: Diagnosis of porphyria cutanea tarda established before enrollment
Overall Study
| Stage | Hydroxychloroquine | Phlebotomy |
|---|---|---|
| STARTED | 16 | 32 |
| COMPLETED | 13 | 17 |
| NOT COMPLETED | 3 | 15 |
Reasons for not completing this period:
| Reason | Hydroxychloroquine | Phlebotomy |
|---|---|---|
| Noncompliance or remission not achieved | 3 | 15 |
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: Gender collected, sex male and female. No race or ethnicity collected
| Characteristic | Unit | Hydroxychloroquine | Phlebotomy | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 17 | 30 | |
| Age, Continuous | years | 50.3 (SD 6.0) | 51.3 (SD 5.0) | 50.9 (SD 5.4) |
| Sex: Female, Male: Female | Participants | 8 | 2 | 10 |
| Sex: Female, Male: Male | Participants | 5 | 15 | 20 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Remission, measured over To end of study, an average of 3 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is time to remission, measured in months. The registry describes remission as a decrease in plasma porphyrin concentration to less than 0.9 mcg/dL. The study summary also describes remission as achieving a normal plasma porphyrin concentration. This makes the endpoint a time-to-event measure: the event is reaching the laboratory threshold, and the outcome is how long that takes.
Time to event can be useful when the timing of an outcome matters, not just whether it occurred. A group median gives the time by which half of the observed event-time distribution has reached or passed the median, subject to the way the analysis handles follow-up and censoring. The registry record does not report those analysis details, so the posted median should be read as a descriptive summary rather than as a complete account of the event-time analysis.
The record gives each group’s median and full range. A full range describes the smallest and largest recorded values in the reported group; it is not a confidence interval and does not quantify the precision of the median. The registry’s stated follow-up was until remission, with a timeframe to the end of the study described as an average of 3 years. Details about censoring, participants who did not reach remission, and how such observations entered the calculation are not reported in the registry record.
A laboratory threshold offers a defined way to mark remission, but the endpoint represents that specific biochemical criterion. It does not, by itself, describe every aspect of the condition or establish how participants felt or functioned.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted median time to remission was 6.1 months for hydroxychloroquine, with a full range from 0.9 to 10.7 months. For phlebotomy, the median was 6.9 months, with a full range from 1.8 to 26.5 months. The registry lists 13 for the hydroxychloroquine arm and 17 for the phlebotomy arm in the primary outcome result. These are descriptive summaries of the posted outcome data.
The medians alone do not establish whether the treatments differ statistically or whether the noninferiority hypothesis was met. A median is a central summary, not an estimate of the size or precision of a between-group effect. The ranges show the span of reported times within each group, but they do not substitute for uncertainty intervals around a treatment comparison. The record does not report a confidence interval, a p-value, a hazard ratio, or a noninferiority margin for this endpoint. Therefore, the registry results do not provide the inferential information needed to assess noninferiority.
In general, noninferiority is a prespecified claim that a treatment is not worse than a comparator by more than an acceptable margin. Evaluating that claim requires the margin and an appropriate estimate of the between-group effect with its uncertainty. A numerical ordering of the two medians is not enough: it does not show whether any difference is compatible with the stated margin or with chance variation. The margin and inferential analysis are not reported in the registry record.
The registry labels the endpoint as time-to-event, but the posted result consists of group medians and ranges. It does not state how censoring was handled, whether all randomized participants contributed to the endpoint analysis, or whether the reported medians came from a survival-analysis estimator. Those omissions matter because event-time summaries can depend on how incomplete follow-up is treated. The record’s summary says patients were followed until remission, but that statement does not supply the participant-level follow-up or analysis details.
The group ranges overlap, but range overlap is not a formal test of a treatment difference. Conversely, non-overlap or overlap of observed ranges cannot by itself settle a noninferiority question. The available results support a descriptive account of the observed remission times, not a conclusion that either regimen is superior, equivalent, or noninferior. No conclusion about clinical benefit should be drawn from the median values alone.
The primary outcome result also does not summarize the secondary outcomes. The registry lists outcomes concerning 50% and 75% reductions in plasma porphyrin level and days with normal urinary porphyrin levels, but their results are not reported in the record information described. Without those findings, they cannot add evidence about the course of laboratory changes. The interpretation should remain limited to the posted remission-time summaries and the absence of a reported inferential comparison.
9. Statistical Methods Explained
The outcome is a time-to-event measure. In general, a time-to-event analysis studies the elapsed time from a defined starting point until a specified event. Here, the registry identifies the event as a plasma porphyrin concentration decrease to less than 0.9 mcg/dL. For this kind of outcome, participants may reach the event at different times, and some may have incomplete event-time information by the end of follow-up. The registry’s summary says patients were followed until remission, but does not describe any censoring or analysis procedures.
What does a median event time describe?
A median is the middle of a distribution of observed times under the relevant method of estimation. It gives a more robust central summary than a mean when times are skewed, as can happen with event-time outcomes. The posted median was 6.1 months for hydroxychloroquine and 6.9 months for phlebotomy. These are group-level descriptions. They do not identify the experience of every participant, and they do not quantify uncertainty in the difference between treatment groups.
The record reports a full range for each group: 0.9 to 10.7 months for hydroxychloroquine and 1.8 to 26.5 months for phlebotomy. In general, a range gives the endpoints of the observed values, so it can be sensitive to unusually early or late observations. It is not a measure of the precision of a median. A confidence interval, when reported, addresses uncertainty in an estimate under a statistical method; a full range instead describes the spread of the reported observations. No confidence interval for the medians or their comparison is reported in the registry record.
Why would a treatment comparison need more than medians?
In general, a treatment comparison requires an estimate of the between-group effect and information about its uncertainty. A test or confidence interval can help distinguish a pattern that is compatible with chance variation from one that is less compatible with a specified statistical model. The registry reports separate medians and ranges, but no reported hazard ratio, confidence interval, or p-value for the primary comparison. A difference in the ordering of medians is descriptive and cannot, by itself, establish an inferential result.
For time-to-event data, a hazard ratio is one possible relative measure comparing event rates over follow-up under a model. It is not interchangeable with a ratio or difference of medians, and its interpretation depends on the analysis and assumptions. The registry’s outcome information does not report a hazard ratio for this trial’s primary endpoint. No additional estimate should be inferred from the medians or ranges.
How does noninferiority differ from a standard difference question?
In general, a noninferiority study asks whether the effect of an intervention is not worse than that of a comparator by more than a prespecified, clinically acceptable margin. The margin is essential to defining the claim; it is not determined by observing the trial results. The registry states a noninferiority hypothesis for hydroxychloroquine relative to phlebotomy, but does not report the margin or the inferential result needed to assess it. Thus, the posted medians cannot be used as a substitute for a noninferiority analysis.
Interpretation of a noninferiority analysis also depends on a clearly specified direction of the effect, the analysis population, and suitable handling of missing outcome information. In general, different analysis populations may be relevant to assessing noninferiority, but the registry record does not report which populations were used or how they were defined. It also does not report a detailed statistical analysis plan. The record therefore does not permit verification of those aspects of the intended analysis.
What can the ranges say about precision?
The full ranges indicate that observed times varied within each group. They do not give the uncertainty around a group median, and their extent is influenced by the number of observations and the values at the extremes. In general, a confidence interval would be more directly relevant to the precision of an estimated median or treatment contrast. The absence of an interval in the registry record means that the precision of the reported group summaries cannot be assessed from the posted result alone.
The registry lists 13 in the hydroxychloroquine outcome record and 17 in the phlebotomy outcome record. Those entries describe the group counts associated with the posted result; the registry does not explain whether the counts represent all randomized participants, all participants with an observed event, or another analysis set. No analysis population definition or accounting of incomplete observations is reported. The registry enrollment of 48 should not be treated as the denominator for this particular endpoint without a report explaining how enrollment relates to the outcome analysis.
What do the secondary outcomes add?
The registry lists three secondary outcomes: 50% reduction in plasma porphyrin level, 75% reduction in plasma porphyrin level, and number of days with normal urinary porphyrin levels. In general, secondary endpoints can describe other aspects of response or provide supporting evidence, but they do not replace the prespecified primary endpoint. Their interpretation depends on definitions, analysis methods, and reported results. The results for these secondary outcomes are not reported in the registry record.
The registry lists four outcome measures and zero analysis entries. That record of entries does not show whether analyses were conducted outside the registry; it indicates that no analysis entries are posted in the registry record. The detailed statistical methods, including the method used to estimate the medians, handling of censoring, model assumptions, and any adjustment for multiple outcomes, are not reported. These are limits on what can be independently interpreted from the posted result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures: the primary remission outcome and three secondary outcomes concerning plasma porphyrin reductions and normal urinary porphyrin levels. Considering multiple outcomes can increase the chance of a false-positive finding if many statistical tests are conducted and interpreted without an appropriate plan. In general, a prespecified hierarchy or multiplicity adjustment can address that issue, depending on the study’s aims. No multiplicity strategy or testing hierarchy is reported in the registry record. The secondary outcome results are not reported in the record information, so their statistical relationship to the primary outcome cannot be assessed.
Missing data and incomplete follow-up are also important for a time-to-event endpoint. In general, an analysis needs to distinguish participants who have reached the event from those whose event time is not observed during the available follow-up. The registry summary says patients were followed until remission, but does not report whether any participants had incomplete follow-up, how such observations were handled, or whether reasons for missing information differed by treatment group. The record does not report a missing-data plan.
The registry outcome counts are 13 for hydroxychloroquine and 17 for phlebotomy. The registry does not specify the analysis population or explain how those counts relate to enrollment of 48, randomization, or outcome availability. It does not report whether the analysis followed an intention-to-treat, per-protocol, or other population definition. These details are especially relevant to interpreting a noninferiority question, but cannot be reconstructed from the posted record.
The registry lists zero analysis entries. This means analysis details are not posted as registry analysis entries; it does not establish that no analyses were performed. A statistical analysis plan, data completeness information, and the handling of protocol deviations are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Hydroxychloroquine | 4 | 13 | 30.8% |
| Phlebotomy | 0 | 17 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Hydroxychloroquine | 1 of 13 |
| Phlebotomy | 0 of 17 |
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 |
|---|---|
| Hydroxychloroquine | 3 of 13 |
| Phlebotomy | 0 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | Hydroxychloroquine | Phlebotomy |
|---|---|---|---|
| Coronary disease | Cardiac disorders | 2 of 13 | 0 of 17 |
| Death | General disorders | 1 of 13 | 0 of 17 |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 13 | 0 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Hydroxychloroquine | Phlebotomy |
|---|---|---|---|
| Suicidal thoughts | Psychiatric disorders | 1 of 13 | 0 of 17 |
| Chest pain | General disorders | 1 of 13 | 0 of 17 |
| Pruritis | Skin and subcutaneous tissue disorders | 1 of 13 | 0 of 17 |
Serious events with the highest arm-level rate: coronary disease (15.4%), death (7.7%), prostate cancer (7.7%).
The registry reports serious adverse event counts for the hydroxychloroquine and phlebotomy groups. It lists 4 serious adverse events in the hydroxychloroquine group and 0 in the phlebotomy group. The corresponding other adverse event counts are 3 and 0, and the death counts are 1 and 0. These are descriptive registry counts; they do not establish that an event was caused by an intervention.
The registry also lists serious adverse event terms with percentages: coronary disease, 15.4%; death, 7.7%; and prostate cancer, 7.7%. These entries should be read as the terms and percentages recorded, not as a comparative risk analysis. The record information does not provide a statistical comparison or explain the attribution process, timing, severity criteria, or relationship of each term to treatment.
Counts in different safety categories should not be added to estimate the number of affected people. The registry does not state whether categories overlap or whether a participant could contribute to more than one term. The group counts also provide limited context about uncommon events, particularly without a prespecified comparative analysis and full follow-up detail. A zero recorded count in a group does not demonstrate that the underlying risk is zero. The registry safety entries are a description of reported events, not a causal conclusion or a basis for individual treatment decisions.
12. What the Result Does, and Does Not, Mean
The posted results describe the time to a laboratory-defined remission in the two randomized groups. The median was 6.1 months for hydroxychloroquine and 6.9 months for phlebotomy. The full ranges were 0.9 to 10.7 months and 1.8 to 26.5 months, respectively. These summaries show the reported central times and observed spans, but they do not give a formal estimate of the treatment contrast or its precision.
The trial’s stated hypothesis was noninferiority of hydroxychloroquine to phlebotomy in time to remission. The registry record does not report a noninferiority margin, confidence interval, p-value, or hazard ratio for that comparison. Therefore, the posted medians do not establish that hydroxychloroquine was noninferior, nor do they establish superiority, equivalence, or inferiority. A formal conclusion would require the relevant analysis and its uncertainty, together with the prespecified margin.
In general, a randomized design supports a fairer comparison by assigning treatment independently of known and unknown participant characteristics, but randomization alone does not supply the missing inferential result. It also does not remove concerns about incomplete outcome data, deviations from assignment, or analysis choices. The registry does not report the analysis population, censoring approach, or detailed methods used to obtain the medians.
The posted outcomes should be interpreted within their scope. Remission is defined through plasma porphyrin concentration; the result does not summarize all possible clinical outcomes. Secondary measures are listed, but their results are not reported in the registry record. The safety information is descriptive and does not prove that an event was or was not caused by treatment.
Accordingly, the record supports a limited descriptive reading: it reports group-specific remission-time summaries and safety counts. It does not support a definitive conclusion about comparative efficacy, noninferiority, or causal safety differences. Those limits reflect the information reported in the registry, not a claim that further analyses or information do not exist elsewhere.
13. Why This Trial Matters Statistically
This trial is statistically notable because its central question is noninferiority, while the posted primary outcome information consists of separate group medians and full ranges. Noninferiority is not established by observing that two medians are numerically close. It requires a defined margin and an inferential comparison that quantifies uncertainty relative to that margin. The registry states the noninferiority hypothesis but does not report the margin or the comparison needed to evaluate it.
The endpoint is also a time-to-event measure, which raises issues beyond comparing simple averages. In general, follow-up, censoring, and the method used to estimate event times can affect interpretation. The registry reports follow-up until remission in its summary and gives a timeframe to the end of the study described as an average of 3 years, but the statistical handling of incomplete follow-up is not reported. Readers therefore cannot determine from the registry outcome entry how the reported medians were estimated or whether every participant contributed to the analysis.
The randomized, parallel design offers a clear framework for comparing the two specified regimens. The posted information also makes visible the distinction between an outcome’s descriptive summaries and evidence from a prespecified statistical test. Reporting medians and ranges is useful for conveying observed event times, but those summaries alone do not answer the inferential question posed by a noninferiority hypothesis.
The registry lists secondary laboratory outcomes and safety events as well. Their presence highlights why outcome definitions, multiplicity plans, analysis populations, and complete reporting matter: multiple endpoints can address different aspects of a trial, but each needs interpretable methods and results. The registry record does not report those details for the secondary outcomes. Statistically, the main lesson is to distinguish the question the design set out to answer from the limited summaries available in the posted results.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record does not report a noninferiority margin, a confidence interval, a p-value, or a hazard ratio for the primary comparison. As a result, the posted group summaries cannot establish the stated noninferiority hypothesis. The method used to calculate the medians is also not described, and the record does not explain how censoring or incomplete follow-up was handled.
The outcome record lists 13 for hydroxychloroquine and 17 for phlebotomy, but does not define the analysis population or explain how those counts relate to enrollment of 48. The record does not report participant flow, reasons for any exclusions, protocol deviations, treatment discontinuation, adherence, or missing outcome information. These omissions limit assessment of how representative the reported outcome summaries are of the randomized groups.
The registry describes remission using a plasma porphyrin threshold and also uses the phrase normal plasma porphyrin concentration in its study summary. The record does not provide further detail about measurement procedures, assessment timing, or confirmation of the threshold. It lists secondary outcomes but does not report their results or statistical methods. No multiplicity plan or detailed analysis plan is reported.
The study is described as unmasked, but the registry does not explain whether outcome assessment was masked or how the laboratory endpoint was measured. The record’s safety entries are counts and listed terms; it does not report comparative safety analyses, event attribution methods, or fuller event narratives. Finally, the primary outcome timeframe is described as to study end, with an average of 3 years, but details about individual follow-up are not reported. These limits constrain interpretation of the registry record and should not be mistaken for proof that additional information is unavailable elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Hydroxychloroquine and Phlebotomy for Treating Porphyria Cutanea Tarda — NCT01573754.
- Registry record last updated 2023-02-17; status last verified 2023-02.
- Results first posted 2023-02-17.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry describes a completed randomized, unmasked, parallel-group phase 2 comparison of low-dose hydroxychloroquine and phlebotomy for porphyria cutanea tarda. Enrollment is listed as 48. The primary outcome is median time to remission, defined by a plasma porphyrin concentration decrease to less than 0.9 mcg/dL.
The posted median was 6.1 months for hydroxychloroquine, with a full range of 0.9 to 10.7 months, and 6.9 months for phlebotomy, with a full range of 1.8 to 26.5 months. The registry does not report an inferential comparison or the noninferiority margin. It lists three secondary outcomes, but their results are not reported in the registry record.
The registry includes descriptive serious and other adverse event counts and lists serious event terms. Details of the primary analysis, analysis populations, missing-data handling, multiplicity, and statistical analysis plan are not reported. The posted results therefore support description of the recorded outcome summaries, but not a definitive comparative or noninferiority conclusion.