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 Pyridoxine in Preventing Hand-Foot Syndrome in Patients Who Are Receiving Liposomal Doxorubicin for Cancer (NCT00245050), a randomized phase 3 study. The primary outcome is Number of Participants With Palmar-plantar Erythrodysesthesia (PPE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00245050 |
| Phase | Phase 3 |
| Condition | Breast Cancer, Drug/Agent Toxicity by Tissue/Organ, Endometrial Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 34 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Case Comprehensive Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients receiving liposomal doxorubicin for recurrent ovarian, fallopian tube, or peritoneal cancer, metastatic breast cancer, or advanced endometrial cancer. The registry describes a total enrollment of 34. Patients were eligible for the PPE/HFS incidence and toxicity assessment if they received at least one course of chemotherapy; the record also states that an intention-to-treat analysis was used.
Intervention
Oral pyridoxine hydrochloride, described as 100 mg twice daily on days 1-28. Doxorubicin HCl liposome was also given intravenously at 40 mg/m2 over 1 hour on day 1.
Comparator
Oral placebo on days 1-28, alongside the same described liposomal doxorubicin regimen. The trial was randomized, double-blind, and parallel-group.
Primary question
Among patients receiving liposomal doxorubicin, did the number of participants with palmar-plantar erythrodysesthesia (PPE), also called hand-foot syndrome, differ between those assigned pyridoxine and those assigned placebo? The registry record identifies this as the primary outcome but does not report the treatment-group outcome counts or a comparative estimate.
The clinical question is about prevention or reduction of a treatment-associated toxicity, rather than about the cancer treatment’s effect on the underlying cancers. The record says that participants were monitored for overall and specific doxorubicin-related toxicities, including pyridoxine-related toxicities. Monitoring included weekly phone calls from the research nurse and monthly clinic visits. The planned treatment repeats every 4 weeks for up to 6 courses in the absence of unacceptable toxicity.
The randomized comparison is intended to assess whether outcome frequency differs by assigned supplement while both groups receive liposomal doxorubicin. The trial record does not state a specific hypothesis about the size of a clinically important difference. It also does not report the primary outcome results needed to answer the comparison from the registry record alone.
3. Trial Design
This was a phase 3 randomized, double-blind, parallel-group trial. The registry lists enrollment of 34 and a completed status. The recorded start is 2004-04 and primary completion is 2008-04. Case Comprehensive Cancer Center is named as the sponsor.
Participants were assigned to pyridoxine or placebo while receiving liposomal doxorubicin. The described doxorubicin regimen was 40 mg/m2 intravenously over 1 hour on day 1. In the pyridoxine arm, oral pyridoxine was given at 100 mg twice daily on days 1-28. The placebo arm received oral placebo on days 1-28; the registry describes its schedule as twice 100 mg daily. Treatment was repeated every 4 weeks for up to 6 courses unless unacceptable toxicity occurred.
Randomization is intended to create groups that are comparable, on average, with respect to measured and unmeasured characteristics. Double masking means that the record describes masking of both participants and investigators, though further detail about who remained masked or how masking was maintained is not reported in the registry record. A parallel design assigns participants to one group rather than having each participant receive both study regimens in sequence.
The registry lists cancer conditions including breast, endometrial, fallopian tube, ovarian, and peritoneal cavity cancer, as well as drug or agent toxicity by tissue or organ. Its study summary describes the intended population as patients receiving liposomal doxorubicin for recurrent ovarian, fallopian tube, or peritoneal cancer, metastatic breast cancer, or advanced endometrial cancer. Further eligibility criteria and details of the randomization procedure are not reported in the registry record.
The record lists quality of life measured with the Functional Assessment of Cancer Therapy (FACT-G) as a secondary outcome. It lists 2 outcome measures and 2 analyses, but does not report the analysis methods or the results for quality of life. A sample-size justification and detailed statistical analysis plan 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: Patients were required to have discontinued corticosteroid therapy at least three weeks prior to enrollment and no corticosteroids were allowed for the duration of the trial. Patients must have discontinued pyridoxine therapy at least three weeks prior to enrollment.
Overall Study
| Stage | Pyridoxine | Placebo |
|---|---|---|
| STARTED | 18 | 16 |
| COMPLETED | 15 | 14 |
| NOT COMPLETED | 3 | 2 |
Reasons for not completing this period:
| Reason | Pyridoxine | Placebo |
|---|---|---|
| Adverse Event | 3 | 2 |
Analysis population for the primary outcome, as defined in the registry: Patients were evaluable for PPE/HFS(Hand-Foot Syndrome) incidence and toxicity assessment if they received at least one course of chemotherapy. Intention to treat analysis was used.
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 | Pyridoxine | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 18 | 16 | 34 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 | 6 | 14 |
| Age, Categorical: >=65 years | Participants | 10 | 10 | 20 |
| Age Continuous | years | 62.9 (SD 9.4) | 65.9 (SD 11.0) | 64.3 (SD 10.2) |
| Sex: Female, Male: Female | Participants | 18 | 16 | 34 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 18 | 16 | 34 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Palmar-plantar Erythrodysesthesia (PPE), measured over Treatment repeats every 4 weeks for up to 6 courses in the absence of unacceptable toxicity..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants with palmar-plantar erythrodysesthesia, abbreviated PPE and also called hand-foot syndrome. It is a count of participants experiencing the toxicity, rather than a continuous measurement of symptom severity. The registry describes PPE incidence and toxicity assessment as the outcome focus and states that participants were monitored for overall and specific doxorubicin-related toxicities using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0.
General: A binary endpoint records whether each participant experienced the event or did not. The number of participants with an event can then be compared between assigned groups. Such endpoints are useful for communicating how many people experienced a clinically relevant event, but a count alone does not convey the severity, duration, or timing of each participant's symptoms. Those details require separate outcome definitions or results.
The registry specifies a treatment timeframe of repeating courses every 4 weeks for up to 6 courses in the absence of unacceptable toxicity. It does not give a more specific primary-outcome assessment timepoint or define how multiple episodes in one participant were handled. The arm-specific participant counts for PPE and a treatment comparison are not reported in the registry record. Accordingly, the primary endpoint is identifiable, but its comparative result cannot be interpreted from the posted outcome information in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes that the trial was designed to compare pyridoxine with placebo for PPE among patients receiving liposomal doxorubicin. It reports the study design, treatment schedules, outcome definition, and monitoring approach. However, it does not report the number of participants with PPE in either group, an effect estimate comparing groups, a confidence interval, or a p-value. There is therefore no registry-reported primary outcome result to interpret as evidence for or against a difference between the assigned groups.
The enrollment figure is 34, but enrollment alone does not indicate how many participants contributed to the primary outcome analysis or how many experienced PPE. The record says that patients were evaluable for PPE/HFS incidence and toxicity assessment if they received at least one course of chemotherapy, and that an intention-to-treat analysis was used. The relationship between that evaluability statement and the analysis set used for the posted primary outcome is not explained in further detail.
General: A group-specific event count describes the observed frequency of an outcome in that group. A comparative estimate describes the difference or other contrast between groups, while a confidence interval conveys the range of values reasonably compatible with the data under the statistical model. A p-value, when reported, addresses how compatible the data are with a specified null hypothesis under the assumptions of a test. None of these primary-outcome comparison statistics appears in the registry information.
The safety counts are reported separately from the primary outcome. They show serious and other adverse-event counts for the named treatment groups, but they cannot substitute for PPE results. Nor do those counts by themselves establish that an adverse event was caused by a study treatment. The listed serious-event terms have percentages, but the registry information does not specify their denominators or provide enough detail to interpret those percentages as participant-level risks for a particular arm.
The record lists quality of life measured by FACT-G as a secondary outcome, but does not report its results. It also does not report a protocol-based sample-size justification, interim analyses, or detailed statistical methods. The conclusions that can be drawn from this registry record are therefore limited: it documents a randomized comparison intended to address the prevention question, but the primary outcome comparison and secondary quality-of-life findings are not reported in the information available for this analysis.
9. Statistical Methods Explained
The trial’s design and outcome definitions determine what a statistical comparison could mean. The registry describes randomized allocation, double masking, and a parallel-group comparison of pyridoxine with placebo. It defines the primary outcome as the number of participants with PPE. The record does not report the statistical test or model used to compare the groups, so no particular analysis method should be attributed to the investigators.
What does randomization contribute?
General: Randomization assigns treatment without deliberately choosing a participant’s group based on their characteristics. If allocation is implemented as planned, it helps balance prognostic factors between groups on average and supports a causal interpretation of a treatment contrast. It does not guarantee that small groups will be identical, nor does it prevent problems caused by missing outcome information, departures from assigned treatment, or differences in outcome measurement. The allocation procedure and any concealment details are not reported in the registry record.
What does masking contribute?
General: Masking can reduce the chance that knowledge of assignment influences participants’ reports, clinical care, or outcome assessment. The registry labels the study double-blind, but does not identify all masked roles or describe procedures for maintaining masking. PPE was assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0; the record says participants were monitored weekly by phone and monthly at clinic visits.
How should a binary endpoint be analyzed?
General: For a binary outcome, each participant is classified as having or not having the event according to the outcome definition. Analysts may compare the event frequencies across randomized groups using a difference in proportions, a relative measure, or a regression model. Each approach answers a related but distinct question and depends on assumptions and analysis choices. The registry does not report which measure or model was selected, nor does it report the event counts needed to describe a comparison.
In this trial, the endpoint title refers to the number of participants with PPE. It is not a count of symptom episodes, a severity score, or a time-to-first-event outcome as described in the record. The stated treatment schedule allows repeated courses, but the registry does not explain whether the primary endpoint covered any PPE during treatment, a particular course, or another prespecified window. The precise primary-outcome assessment timepoint is not reported in the registry record.
Why do uncertainty estimates matter?
General: An estimate from a trial is subject to sampling variability: another study of similar participants could yield a different estimate. A confidence interval expresses uncertainty around an estimate and helps readers assess both its precision and the range of effects compatible with the observed data. A narrow interval generally indicates greater precision than a wide one, but interpretation also depends on the endpoint, analysis, and study design. Because the primary comparison estimate and its interval are not reported, its precision cannot be assessed from this record.
A p-value is not a measure of effect size and does not state the probability that a treatment hypothesis is true. It summarizes how unusual the observed data would be under a specified null model and its assumptions. The registry information does not report a p-value or the statistical procedure used to generate one. No conclusion about statistical significance can be drawn from the reported primary-outcome details alone.
What does the analysis population mean?
The record states that patients were evaluable for PPE/HFS incidence and toxicity assessment if they received at least one course of chemotherapy, and that an intention-to-treat analysis was used. General: An intention-to-treat approach usually analyzes participants according to their randomized assignment, regardless of treatment received after randomization. Its exact implementation depends on the protocol and available outcome data. The record does not explain how participants who received no course, discontinued treatment, or had missing PPE assessments were handled in the primary analysis.
The eligibility language and the statement about intention-to-treat therefore need to be read as separate pieces of information. The first describes who was considered evaluable for incidence and toxicity assessment; the second describes the analysis approach stated by the registry. Without the analysis counts and missing-data handling details, the precise population contributing to the primary comparison cannot be reconstructed.
What can sample-size planning tell us?
General: Sample-size planning concerns how many participants a future or planned study would need under specified assumptions about the event rate, effect size, allocation, significance level, and desired power. Such planning is not the same as an observed result and does not show whether a trial’s actual findings are precise. The registry notes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The planning illustration is not the trial’s own design justification. Numerical planning results and the assumptions underlying the original trial design are not reported in the registry record.
Likewise, interim analyses, multiplicity adjustments, and a complete statistical analysis plan are not reported. These omissions limit the ability to determine which analysis choices were prespecified or how the investigators intended to address multiple outcomes or repeated assessment. The description should not be extended beyond what the registry records.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures and 2 analyses, with quality of life measured by FACT-G identified as a secondary outcome. It does not report a complete list of statistical hypotheses, the testing sequence, or a method for controlling the chance of false-positive findings across multiple outcomes. A multiplicity strategy is therefore not reported in the registry record. This does not establish that no such strategy existed; it means the record does not describe one.
Missing-data procedures are also not reported. The record says participants were evaluable for PPE/HFS incidence and toxicity assessment if they received at least one course of chemotherapy, and that an intention-to-treat analysis was used. It does not state how missing outcome assessments were classified, whether any imputation was used, or how participants who did not receive a course were handled in that analysis. The number of participants with missing primary or secondary outcome data is not reported.
General: Missing outcome data can affect a treatment comparison if the likelihood of missingness is related to treatment assignment or to the outcome. An intention-to-treat label does not, by itself, specify how missing values are addressed. Similarly, collecting repeated toxicity assessments does not establish that all timepoints were included in one endpoint or analysis; the registry does not give details of the primary assessment window or any repeated-measures methods.
The registry does not report interim analyses, stopping rules, or a detailed statistical analysis plan. Those omissions prevent a reader from assessing whether analyses were prespecified, how multiple comparisons were handled, or what sensitivity analyses were planned. No assumptions about these procedures can be made from the record’s design description alone.
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 |
|---|---|---|---|
| Pyridoxine | 8 | 15 | 53.3% |
| Placebo | 6 | 14 | 42.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pyridoxine | 13 of 15 |
| Placebo | 10 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | Pyridoxine | Placebo |
|---|---|---|---|
| Blood/bone marrow | Blood and lymphatic system disorders | 1 of 15 | 2 of 14 |
| Gastrointestinal | Gastrointestinal disorders | 2 of 15 | 0 of 14 |
| Vascular | Vascular disorders | 1 of 15 | 1 of 14 |
| Allergy/immunologic | Immune system disorders | 0 of 15 | 1 of 14 |
| Constitutional symptoms | General disorders | 0 of 15 | 1 of 14 |
| Hemorrhage/bleeding | Blood and lymphatic system disorders | 1 of 15 | 0 of 14 |
| Infection | Infections and infestations | 1 of 15 | 0 of 14 |
| Metabolic/laboratory | Metabolism and nutrition disorders | 0 of 15 | 1 of 14 |
| Neurology | Nervous system disorders | 1 of 15 | 0 of 14 |
| Pulmonary/upper respiratory | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 0 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pyridoxine | Placebo |
|---|---|---|---|
| Blood/bone marrow | Blood and lymphatic system disorders | 7 of 15 | 8 of 14 |
| Gastrointestinal | Gastrointestinal disorders | 9 of 15 | 5 of 14 |
| Constitutional symptoms | General disorders | 7 of 15 | 5 of 14 |
| Pain | General disorders | 5 of 15 | 2 of 14 |
| Pulmonary/upper respiratory | Respiratory, thoracic and mediastinal disorders | 2 of 15 | 4 of 14 |
| Renal/genitourinary | Renal and urinary disorders | 2 of 15 | 3 of 14 |
| Lymphatics | Blood and lymphatic system disorders | 2 of 15 | 2 of 14 |
| Neurology | Nervous system disorders | 3 of 15 | 1 of 14 |
| Infection | Infections and infestations | 2 of 15 | 1 of 14 |
| Hepatic/pancreas | Hepatobiliary disorders | 0 of 15 | 2 of 14 |
Serious events with the highest arm-level rate: blood/bone marrow (14.3%), gastrointestinal (13.3%), allergy/immunologic (7.1%), constitutional symptoms (7.1%), metabolic/laboratory (7.1%).
The registry reports safety counts separately for the pyridoxine and placebo groups. For pyridoxine, 15 participants were listed as at risk for serious events and 8 as affected; 15 were listed as at risk for other events and 13 as affected. For placebo, 14 were listed as at risk for serious events and 6 as affected; 14 were listed as at risk for other events and 10 as affected. These are the reported counts, not estimates of treatment effect. Death counts are listed as null for both groups.
The serious-event terms with the largest listed percentages are Blood/bone marrow at 14.3%, Gastrointestinal at 13.3%, Allergy/immunologic at 7.1%, Constitutional symptoms at 7.1%, Metabolic/laboratory at 7.1%, and Vascular at 7.1%. The registry information does not identify the denominators for these percentages or give arm-specific counts for each listed term. The terms should not be interpreted as mutually exclusive categories or as evidence that an event was caused by a study treatment.
General: Safety counts depend on how events were defined, collected, and assigned to categories. A participant may experience more than one event, so event counts and counts of affected participants are not necessarily interchangeable. The registry does not provide enough detail to determine the extent of overlap among categories or to compare specific event types between groups. Safety observations should be read alongside the trial’s monitoring description and the limits of the reported information.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized, double-blind trial asking whether pyridoxine could prevent or lessen PPE among patients receiving liposomal doxorubicin. It establishes the treatment groups, the primary endpoint, and the general monitoring approach. Those design details clarify the intended comparison, but they do not reveal its result.
The primary endpoint is the number of participants with PPE. The record does not report the number affected in either treatment group, a group contrast, an uncertainty interval, or a p-value. Consequently, the posted primary outcome information does not establish whether the observed frequency differed between pyridoxine and placebo, or how precisely any difference was estimated. The absence of a reported comparison in this record is not evidence that there was no difference.
The adverse-event counts describe safety observations but are not a substitute for the primary endpoint result. They also do not, by themselves, establish causation. The listed FACT-G secondary outcome has no reported results in the information. Thus, the registry description does not support an interpretation of the comparative quality-of-life findings either.
General: A randomized design can support a causal comparison when allocation, follow-up, outcome assessment, and analysis are appropriate. The strength of that interpretation also depends on having sufficiently complete outcome data and a clearly defined analysis. Details about missing data, the primary assessment window, and the statistical model are not reported in the registry record. Without the outcome estimates and these methodological details, readers cannot assess the magnitude, uncertainty, or robustness of the trial’s primary finding.
The trial’s enrollment of 34 is a description of the study, not a statement about its precision or ability to detect a difference. The record does not report the original sample-size justification. Any planning illustration based on an observed effect should be treated as planning information, not as observed power or as a substitute for a confidence interval around a trial estimate. The available information therefore supports a description of the study question and design, but not a conclusion that pyridoxine did or did not prevent PPE.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how a focused prevention question can be framed within a randomized comparison. Both groups received the described liposomal doxorubicin regimen, while the assigned supplement differed. The primary outcome was an event count at the participant level: the number with PPE. Randomization and double masking are design features intended to make the comparison less vulnerable to systematic differences in assignment and assessment.
The record also illustrates why a study design and a result are not interchangeable. Knowing the endpoint, treatment schedules, enrollment, and follow-up approach does not disclose the treatment contrast. To assess the statistical evidence, readers need the group-specific outcome counts and an estimate of the comparison with its uncertainty. Those primary results are not reported in the registry information used.
There is also a distinction between statistical planning and observed evidence. The registry describes a planning illustration based on an observed effect, but does not report the original design justification or numerical planning results. Planning assumptions can help explain what a study was designed to detect, but cannot determine whether the eventual estimate was precise or whether a result is clinically important. The outcome estimate and its interval are essential to those judgments.
Finally, the record highlights the importance of documenting analysis populations, missing-data handling, multiplicity, and endpoint timing. It states that an intention-to-treat analysis was used and describes an evaluability condition, but does not explain missing-data procedures or the precise outcome assessment window. These details affect how a result should be understood. The trial’s statistical value cannot be judged solely from the randomized label; transparent reporting of outcomes and analysis is needed to interpret the comparison.
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 central limitation for interpretation is that the registry record does not report the primary outcome counts by group or a comparative estimate. Without those results, the main prevention question cannot be answered from the record. The secondary FACT-G outcome is identified, but its results are also not reported.
The outcome description gives the assessment approach and treatment timeframe, but does not specify a precise PPE assessment window or explain how repeated events were represented. It is therefore unclear from the registry record whether the primary count corresponds to any PPE during treatment or another defined period. The criteria for severity thresholds contributing to the primary endpoint are not described beyond the reference to CTCAE version 3.0.
The record states both that patients were evaluable for PPE/HFS incidence and toxicity assessment if they received at least one course and that an intention-to-treat analysis was used. It does not explain how these statements were applied together, how participants with missing assessments were handled, or how many participants contributed to each outcome analysis. Further eligibility details, randomization procedures, and masking-maintenance procedures are not reported.
The registry information does not describe a statistical analysis plan, sample-size justification, multiplicity adjustment, interim analyses, or sensitivity analyses. The serious-event percentages are listed without their denominators or arm-specific counts by term, limiting interpretation of those categories. These reporting gaps do not prove that procedures or analyses were absent; they mean they cannot be assessed from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pyridoxine in Preventing Hand-Foot Syndrome in Patients Who Are Receiving Liposomal Doxorubicin for Cancer — NCT00245050.
- Registry record last updated 2011-12-30; status last verified 2011-12.
- Results first posted 2010-12-22.
- 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
NCT00245050 is a completed phase 3, randomized, double-blind, parallel-group trial sponsored by Case Comprehensive Cancer Center. The record lists enrollment of 34, a start of 2004-04, and primary completion of 2008-04. It compared oral pyridoxine with placebo in patients receiving liposomal doxorubicin for the cancers described in the study summary.
The primary outcome was the number of participants with PPE/HFS. The registry describes toxicity monitoring by weekly phone calls and monthly clinic visits, and lists FACT-G quality of life as a secondary outcome. It states that an intention-to-treat analysis was used.
Serious and other adverse-event counts are reported by treatment group, but primary PPE counts, a comparative estimate, and quality-of-life results are not reported in the registry record. Details of missing-data handling, multiplicity, and the statistical analysis plan are also not reported.