Study of High Dose Vitamin C On Outcome in Cardiac Surgery Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of High Dose Vitamin C On Outcome in Cardiac Surgery Patients (NCT01167569), a randomized phase 4 study. The primary outcome is Mortality.

2. Clinical Question

The central statistical question is whether the recorded frequency of 30-day mortality differed between the randomized ascorbic-acid and placebo groups. The registry reports zero deaths in each arm and a risk difference of 0.0. This is a description of the posted outcome, not evidence that the treatments are equivalent or that either treatment changes mortality.

The trial also lists renal insufficiency as a secondary outcome. A result for that outcome is not reported in the registry record. The entry identifies cardiac surgery patients and a concern about complications after surgery, but does not report the types of cardiac operations, detailed enrollment criteria, or subgroup-specific questions. Those omissions limit how narrowly the clinical question can be framed.

3. Trial Design

The record describes a randomized, quadruple-masked, parallel-group study of intravenous ascorbic acid in cardiac surgery patients. It is classified as Phase 4 and lists Rutgers, The State University of New Jersey, as sponsor. The study is marked completed. Its start is recorded as 2007-10 and its primary completion as 2013-04.

The ascorbic-acid arm received 10mg/kg x 2 in the operating room, then 5mg/kg every 4 hours x 48 hours. The comparator arm received placebo, described as 5% Dextrose Water or Normal Saline, x 2 in the operating room and every 4 hours X 48 hours. The registry identifies the comparator as placebo. The record does not report how the random sequence was generated, how allocation was concealed, or which roles were included in the quadruple masking.

Enrollment is listed as 57. For the primary outcome, the arm entries list 28.0 participants in the ascorbic-acid group and 29.0 in the placebo group. The outcome is mortality measured over 30 days after surgery. The record also names renal insufficiency as a secondary outcome, but does not report a result for it.

Details about the study's sample-size justification, planned statistical model, interim analyses, monitoring procedures, or prespecified analysis populations are not reported in the registry record. The design labels establish the broad structure of the trial, but do not answer those more specific methodological questions.

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

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Mortality, measured over 30 days.

The primary endpoint is the number of participants who expire within 30 days of surgery. The description explicitly includes patients who remain in hospital and patients who have been discharged. The registry reports zero events in the ascorbic-acid arm and zero in the placebo arm.

Mortality is a binary outcome for each participant: the event either occurred within the specified period or it did not. Reporting the number of participants with the event makes the endpoint directly interpretable as a count. Comparing the arms can describe whether the observed event frequency differs between randomized groups. The posted comparison uses a risk difference, a measure of the difference between event proportions.

As a general statistical point, a prespecified time window helps define which events belong to an endpoint. Here, the window is 30 days after surgery. Events outside that period are not part of the stated primary endpoint. The record does not describe how deaths were ascertained, whether any participants had incomplete follow-up, or how such cases would be handled.

The registry also names renal insufficiency as a secondary outcome, but no result for it is reported in the registry record. The primary mortality result therefore cannot stand in for findings on renal insufficiency or other postoperative complications.

7. Results Posted in the Registry

• A-Ascorbic Acid (Vitamin C): 0.0% (0/28) versus 0.0% (0/29) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants with a binary event: death within 30 days after surgery. The record gives the number of events and the group size for each arm. It also reports a risk-difference comparison. These summaries address the same basic question in different forms: the counts describe observed events, while the risk difference describes the contrast between the groups' event proportions.

What does a risk difference express?

As a general statistical explanation, a risk difference is the event proportion in one group minus the event proportion in the comparison group. A value of 0.0 indicates that the reported proportions are the same in the posted comparison. In this trial, the reported event counts are zero in each arm, and the reported risk difference is 0.0. No additional calculation is needed to describe that result.

The registry labels the comparator as OG001, corresponding to the placebo arm, and the comparison lists the placebo group as n0 29.0 and the ascorbic-acid group as n1 28.0. Those labels identify the groups used in the posted comparison; they do not provide the missing details of an analysis method. The registry does not report whether the comparison was adjusted for any baseline variables, or whether a different model was used for the primary analysis.

How should zero events be understood?

As a general statistical point, observing no events in a group does not establish that the underlying event probability is zero. It means that no events were recorded for that group in the available outcome data. When both groups have no events, the observed contrast is zero, but the data offer little direct information about how the treatments compare in circumstances where the event occurs. Statistical methods can represent uncertainty around sparse-event estimates in different ways. Which approach was used for the posted limits is not reported in the registry record.

The posted comparison gives an estimate of 0.0 and limits of 0.0 and 0.0. The registry record does not state the confidence level, formula, or software used. Without that information, readers cannot determine whether the limits reflect a conventional confidence interval, another interval procedure, or a transcription or reporting convention. The limits should be quoted as reported rather than interpreted as a guarantee that there is no uncertainty.

What information is missing about the analysis?

The record does not report a p-value, a statistical analysis plan, an adjusted model, or the approach used for missing outcomes. It does not state whether the primary analysis followed intention-to-treat principles, used a per-protocol population, or applied another population definition. The registry lists zero analysis entries, which does not establish that no analysis was performed; it means that analysis details are not available in the registry record.

The listed enrollment is 57, and the primary-outcome arm entries show 28.0 and 29.0 participants. Those entries alone do not reveal whether all enrolled participants were included in the endpoint analysis, how many had complete follow-up, or how deaths after discharge were verified. The endpoint description says that both inpatients and discharged patients are included, but does not explain the ascertainment process.

What does the planning description mean?

The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect and distinguishes participant counts per arm from total event counts for time-to-event settings. No planning results or fraction-specific values are reported in the registry record. These assumptions describe an illustration, not the trial's own sample-size justification, which is not reported.

As a general statistical explanation, a planning calculation estimates how many participants might be needed under specified assumptions to detect an effect with a chosen probability. Such a calculation is not observed power and cannot repair uncertainty in the trial's result. A planning justification based on a target effect would require details about the expected event rate and the effect considered important; those details are not reported.

Randomization and masking are design features, not analysis methods. The registry identifies the study as randomized and quadruple-masked, but does not report sequence generation, allocation concealment, masking roles, stratification, or procedures for assessing whether masking was maintained. These details matter when evaluating how the comparison was conducted, but should not be inferred from the design labels alone.

10. Confidence Intervals and Precision

The posted primary comparison reports a risk difference of 0.0, with limits of 0.0 and 0.0. The registry record does not identify these limits as a confidence interval, state a confidence level, or describe the method used to obtain them. For that reason, they can be reported as the registry's limits, but their statistical interpretation cannot be fully evaluated from the available record.

As a general explanation, a confidence interval is a range constructed by a statistical procedure to represent uncertainty about an estimate. Its meaning depends on the method, assumptions, and confidence level. A narrow interval can indicate greater precision when those elements are known and the method is appropriate. A pair of identical reported limits should not automatically be read as evidence that the underlying effect is known without uncertainty.

That caution is especially relevant because the primary event count is zero in both arms. With no observed deaths, the observed risk difference is 0.0, but the data do not directly show how the groups would compare in situations where deaths occur. Different methods can behave differently with sparse or absent events. The registry does not report enough detail to assess whether the stated limits capture that uncertainty.

The group entries list 28.0 participants for ascorbic acid and 29.0 for placebo. The record does not report missing-outcome counts, loss to follow-up, or the number of participants included in the analysis. These omissions affect the ability to assess precision and completeness. A point estimate and interval alone cannot resolve those questions.

The appropriate reading is therefore descriptive: no 30-day deaths were recorded in either arm, and the registry reports a risk difference of 0.0 with limits of 0.0 and 0.0. The limits should not be treated as a demonstration of equivalence or as a precise estimate of effects in other cardiac surgery populations.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies mortality as the primary outcome and renal insufficiency as a secondary outcome. It lists 2 outcome measures, while one secondary outcome is posted. A result for renal insufficiency is not reported in the registry record. No additional secondary-outcome findings are available in the record.

As a general statistical point, testing or estimating multiple outcomes can raise multiplicity concerns: when many questions are examined, the chance of at least one apparently notable result can increase. Researchers may address this through a prespecified hierarchy, adjustment, or other strategy. The registry record does not report a multiplicity plan, identify which outcomes were included in any formal analysis, or state whether any adjustment was used. No claim about multiplicity control can therefore be made.

The registry does not report missing-data counts or methods for handling missing outcomes. The primary endpoint description includes deaths among both hospitalized and discharged patients, but it does not state whether every participant's 30-day status was known or how unavailable status was handled. The record also does not report withdrawals or loss to follow-up.

Analysis populations are not described. The enrollment entry is 57, and the primary-outcome arm entries list 28.0 and 29.0 participants, but the registry does not explain whether those entries define the analysis population or whether any participants were omitted from the endpoint analysis. It does not state whether the analysis was intention-to-treat, per-protocol, or based on another definition.

The registry lists zero analysis entries. That absence of posted analysis details should not be interpreted as proof that the investigators performed no statistical analyses. It means that the registry record does not provide those details. As a result, readers can describe the posted outcome counts and comparison, but cannot assess how missing data, analysis populations, or multiple outcomes were handled.

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.

The adverse-event entries list zero serious events and zero other adverse events in each group. The entries also list zero deaths for both groups. The at-risk counts are 28 for the ascorbic-acid group and 29 for the placebo group. These are registry counts and should be read as recorded, rather than as evidence that no adverse events could occur.

As a general statistical point, safety counts describe observed events in the recorded groups over the period and under the reporting definitions used. They do not by themselves establish that the treatments have identical safety profiles. Interpretation depends on how events were defined, monitored, collected, and attributed, as well as on the duration and completeness of follow-up. Those details are not reported in the registry record.

The record does not list any top serious adverse-event terms. It also does not provide event-specific descriptions, timing, severity grades, or information about whether events were considered related to study treatment. Therefore, the absence of listed events should be understood as a report of zero recorded counts in the registry entries, not as proof of no risk or as a comparison that rules out differences.

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

The posted data show zero recorded deaths within 30 days of surgery in both the ascorbic-acid and placebo groups. The reported risk difference is 0.0, and the reported limits are 0.0 and 0.0. This is the result for the stated primary outcome in the registry record.

The result does not establish that the underlying mortality risks are equal. When no events are recorded in either group, the observed data do not reveal how the treatments compare in settings where deaths occur. The interval method and confidence level are not reported, so the limits cannot be used to claim that any clinically relevant difference has been ruled out.

The result also does not show that ascorbic acid improves or worsens outcomes. The posted mortality comparison contains no event separation, and the registry record does not provide a p-value or a described analysis method. In keeping with the available information, the conclusion should remain descriptive rather than a claim of treatment effect.

Mortality is not the only outcome named in the record. Renal insufficiency appears as a secondary outcome, but its result is not reported in the registry record. The zero mortality counts do not provide evidence about renal insufficiency or any other postoperative complication.

Finally, the record leaves important questions unanswered about outcome ascertainment, missing data, the analysis population, and the statistical plan. The design is described as randomized and quadruple-masked, but the methods used to implement those features are not reported. These limitations constrain the strength and scope of any interpretation beyond the recorded counts.

14. Why This Trial Matters Statistically

This trial illustrates a basic challenge in interpreting binary clinical outcomes: an observed risk difference of 0.0 is not, by itself, proof that the true risks are the same. Here, the primary endpoint records zero deaths in each group. That makes the observed comparison easy to describe, but leaves the result unable to show how the groups would compare when the event occurs.

The record also illustrates why uncertainty methods matter. The reported risk-difference limits are 0.0 and 0.0, yet the confidence level and method are not reported. In general, statistical intervals depend on their construction and assumptions. With zero events in both arms, the numerical limits deserve particular caution; they should not be mistaken for evidence of certainty or equivalence without the method being known.

Another statistical lesson is the difference between a design label and a fully described analysis. Randomization and quadruple masking are reported, but the registry does not explain sequence generation, concealment, masking roles, missing-data handling, or analysis populations. Those details help readers judge the credibility and scope of a treatment comparison.

The trial also names renal insufficiency as a secondary outcome without reporting its result. This emphasizes that a result for one endpoint cannot substitute for results on other outcomes, and that a registry entry may leave multiplicity procedures and outcome reporting unclear.

For biostatisticians and clinical researchers, the case underscores the importance of complete reporting alongside concise numerical summaries. Counts, group sizes, endpoint definitions, confidence procedures, and analysis populations are all needed to interpret a result appropriately. When some of those elements are absent, conclusions should remain limited to what the recorded data say.

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 primary outcome record gives the event counts and group entries, but does not describe how 30-day mortality was ascertained. The endpoint definition includes patients who remain in hospital and those who have been discharged, yet the registry does not explain follow-up procedures or verification of vital status after discharge. Completeness of outcome follow-up is therefore not reported.

The record lists enrollment as 57, with primary-outcome group entries of 28.0 and 29.0 participants. It does not explain whether all enrolled participants were included in the outcome analysis, or whether any participants had missing outcomes, withdrew, or were excluded. The analysis population and missing-data methods are not reported in the registry record.

Although the study is described as randomized and quadruple-masked, the implementation details are not reported. The record does not identify how the random sequence was generated, how allocation was concealed, or who was masked. It also does not report the analysis model, an adjustment strategy, a p-value, or the method and confidence level for the reported limits.

The registry names renal insufficiency as a secondary outcome but does not report its result. It does not provide a multiplicity plan or enough detail to evaluate whether outcomes were analyzed as prespecified. The record lists zero analysis entries, so the statistical analysis details cannot be assessed from the registry.

Finally, the population and treatment context are described broadly as cardiac surgery patients receiving the stated regimens. Eligibility criteria, types of surgery, baseline characteristics, and subgroup details are not reported. These omissions limit assessment of how broadly the mortality finding can be applied. No sample-size justification or interim-analysis plan is reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of High Dose Vitamin C On Outcome in Cardiac Surgery Patients — NCT01167569.
• Registry record last updated 2020-10-19; status last verified 2020-09.
• Results first posted 2020-10-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01167569 is a completed Phase 4 randomized, quadruple-masked, parallel-group study sponsored by Rutgers, The State University of New Jersey. Its recorded start is 2007-10, and primary completion is recorded as 2013-04. Enrollment is listed as 57.

The study compared intravenous ascorbic acid with placebo in cardiac surgery patients. The primary outcome was mortality within 30 days after surgery. The posted arm entries show zero events in each group, with a risk difference of 0.0 and limits of 0.0 and 0.0. The registry record does not report the confidence level or method for those limits.

Renal insufficiency is listed as a secondary outcome, but its result is not reported in the registry record. Analysis populations, missing-data handling, and further statistical analysis details are also not reported.