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 Vitamin C, Thiamine, and Steroids in Sepsis (NCT03509350), a randomized phase 3 study. The primary outcome is Vasopressor and Ventilator-free Days (VVFD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03509350 |
| Phase | Phase 3 |
| Condition | Sepsis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 501 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
Population
Patients with sepsis enrolled in a multicenter randomized clinical trial. The registry describes the intended population as critically ill patients with sepsis. The primary analysis set was intent-to-treat and included all participants who enrolled.
Intervention
Intravenous vitamin C, thiamine, and hydrocortisone, administered for four days or until ICU discharge, whichever came first.
Comparator
Placebos intended to match the three intervention components, administered for four days or until ICU discharge. The registry notes that treating physicians could initiate open-label corticosteroid therapy during the treatment period when they considered steroids indicated, based on local practice and international guidance.
Primary question
How did the combination protocol compare with the placebo protocol on vasopressor- and ventilator-free days during the first 30 days after treatment began? The endpoint counted days free of both forms of support, assigned zero days to participants who died, and reset the count for participants who returned to ventilation or vasopressors.
3. Trial Design
The VICTAS study is described in the registry as a multicenter, randomized, placebo-controlled, double-blind, adaptive clinical trial. It was a parallel-group Phase 3 trial of combination treatment versus matched placebos in patients with sepsis. The record lists an enrollment of 501 participants and an intent-to-treat primary analysis set that included all participants enrolled. The treatment and control groups included 252.0 and 249.0 participants, respectively.
Participants assigned to the treatment protocol received intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge. The control protocol used matching placebos over the same stated period. The registry also notes that treating physicians could initiate open-label corticosteroids for participants in the control group if an indication existed, according to local practice and international guidance. This allowance is relevant when interpreting the contrast: the randomized assignment was to the protocol, while the record permitted this specified additional treatment in the control group.
The trial is listed as completed. The registry records a start date of 2018-08-22 and a primary completion date of 2019-08-22. Although the study is described as adaptive, the specific adaptation rules, timing, and consequences for the analysis are not reported in the registry record. Details of the randomization procedure beyond randomized allocation, and details of how allocation was concealed, are also not reported in the registry record.
The primary outcome was vasopressor- and ventilator-free days through Day 30. Secondary outcomes included mortality at specified follow-up points, ICU and hospital length of stay, and measures of cognition and delirium. The registry lists 19 outcome measures, with 18 secondary outcomes posted. The individual secondary comparisons should be read as supporting descriptive evidence rather than as a replacement for the primary endpoint.
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 | Treatment Protocol | Control Protocol |
|---|---|---|
| STARTED | 252 | 249 |
| COMPLETED | 252 | 247 |
| NOT COMPLETED | 0 | 2 |
Reasons for not completing this period:
| Reason | Treatment Protocol | Control Protocol |
|---|---|---|
| Withdrawal by Subject | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: This analysis uses an intent-to-treat (ITT) analysis set, which includes all participants who enrolled in the study.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Treatment Protocol | Control Protocol | Total |
|---|---|---|---|---|
| Participants analysed | 252 | 249 | 501 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 148 | 143 | 291 |
| Age, Categorical: >=65 years | Participants | 104 | 106 | 210 |
| Age, Continuous | years | 62 (51 to 69) | 61 (50 to 72) | 62 (50 to 70) |
| Sex: Female, Male: Female | Participants | 113 | 115 | 228 |
| Sex: Female, Male: Male | Participants | 139 | 134 | 273 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 32 | 24 | 56 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 211 | 215 | 426 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 9 | 10 | 19 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 70 | 80 | 150 |
| Race (NIH/OMB): White | Participants | 149 | 135 | 284 |
| Race (NIH/OMB): More than one race | Participants | 33 | 34 | 67 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 252 | 249 | 501 |
6. Primary Endpoint
The registry lists the primary outcome as Vasopressor and Ventilator-free Days (VVFD), measured over Up to Day 30.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint, vasopressor- and ventilator-free days (VVFD), measures the number of days during the first 30 days after treatment began that a participant was alive and free of both vasopressors and mechanical ventilation. The registry says the endpoint was recorded to the nearest day. A participant who died received a score of zero, even if they had previously been alive and free of both supports. If a participant returned to ventilation or vasopressors, the relevant counter was reset to zero days.
This endpoint brings survival and the duration of organ support into one measure. That can make it useful for describing recovery during an acute illness: a larger value represents more days meeting the endpoint definition, while death is handled by the specified zero score. General statistical context: combining outcomes can simplify comparisons, but it also means the endpoint does not distinguish every possible pattern of death and support duration. Different clinical courses may lead to the same VVFD value.
The registry reports medians and interquartile ranges. The treatment group had a median of 25.0 days, with an interquartile range of 0.0 to 29.0; the control group had a median of 26.0 days, with an interquartile range of 0.0 to 28.0. A median describes the midpoint of the observed distribution, while the interquartile range describes its middle half. The record does not provide a reported two-group estimate or confidence interval for this primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results are descriptive: the median VVFD was 25.0 days in the treatment group and 26.0 days in the control group. Their interquartile ranges were 0.0 to 29.0 and 0.0 to 28.0, respectively. These summaries describe the observed distributions, but they do not by themselves quantify the uncertainty in a treatment-versus-control contrast. The registry record does not report an estimable two-arm comparison for this median-time endpoint; it notes that values were missing or not estimable for such a comparison.
Accordingly, the primary results do not include a reported between-group confidence interval or p-value. The medians alone cannot establish whether the groups differ beyond what could arise from sampling variation. The interquartile ranges show that the distributions include substantial variation, but they are not confidence intervals for the group medians or for a treatment effect. No formal claim about a primary treatment effect can be drawn from the posted summaries alone.
The mortality results provide additional, but secondary, context. For mortality at Day 30, the posted treatment-minus-control risk difference is -0.019, with a 95% confidence interval from -0.093 to 0.055. For ICU mortality, the risk difference is 0.010, with a 95% confidence interval from -0.061 to 0.080. For mortality at Day 180, it is 0.027, with a 95% confidence interval from -0.058 to 0.113. Each interval includes zero, the value corresponding to no risk difference. The directions of the point estimates are not consistent across these mortality outcomes. The posted unadjusted p-values are 0.619, 0.79, and 0.532, respectively.
General statistical context: a confidence interval describes a range of values compatible with the data under the method’s assumptions. An interval that includes no difference does not prove that the groups are identical; it indicates that the estimate is not sufficiently precise to exclude no difference at the stated confidence level. The mortality estimates are also secondary and unadjusted, so they should not be treated as definitive evidence on their own.
The registry’s primary endpoint and the mortality outcomes answer related but distinct questions. VVFD incorporates survival and time free of organ support, while mortality outcomes focus on whether death occurred by a specified follow-up point. Differences in the endpoint definitions mean that one cannot substitute the mortality results for a missing primary comparison. Overall, the posted information supports a careful descriptive reading, with uncertainty about the primary between-group contrast left unresolved in the registry record.
9. Statistical Methods Explained
Primary outcome summaries. The primary endpoint is a count of days, but the registry reports it using medians and interquartile ranges. General statistical context: a median is the central observation after values are ordered, and an interquartile range gives the span from the lower to the upper quartile. These summaries are often useful when distributions are skewed or include many observations at a boundary. They describe the data without requiring a mean-and-standard-deviation summary. Here, both groups have an interquartile range beginning at 0.0 days, consistent with the endpoint’s rule that participants who died receive zero and with the possibility of few or no days free of support for some participants.
Median summaries do not automatically yield an appropriate comparison estimate. A comparison may require participant-level data and a method suited to the outcome’s distribution and endpoint rules. The registry says a two-arm comparison was not estimable for this median-time endpoint and does not post a primary confidence interval or p-value. General statistical context: a confidence interval around each group median, even if available, would not be the same as a confidence interval for the difference between groups. The latter is needed to quantify uncertainty in the contrast.
Endpoint construction. VVFD is defined through Day 30 and combines survival with freedom from vasopressors and mechanical ventilation. Death is scored as zero days, and the registry says counters reset for participants who return to either form of support. These rules are part of the endpoint definition, not statistical adjustments made after observing the results. General statistical context: composite or combined outcomes can capture more than one aspect of a clinical course, but interpretation depends on the exact rules. The same total can arise through different sequences of survival and organ support, so the summary does not describe every participant’s course.
Binary mortality comparisons. The posted secondary mortality comparisons express the contrast as a risk difference, with confidence intervals and unadjusted p-values. A risk difference is the difference between the proportions experiencing an event in the two groups; zero represents no difference. The confidence intervals for the three posted mortality comparisons include zero. General statistical context: these intervals convey uncertainty around the risk-difference estimates, while the p-values assess compatibility with a no-difference hypothesis under the calculation’s assumptions. Neither quantity by itself measures clinical importance, and a non-small p-value is not proof of equivalence.
The registry also displays relative risks and odds ratios for the mortality comparisons. These are alternative ways to express a contrast in binary outcomes. A relative risk compares the event probabilities between groups; an odds ratio compares event odds. Their interpretation differs from that of a risk difference, and the numerical values should not be treated as interchangeable. The displayed estimates are based on posted group counts, and the registry lists no reported analyses for these outcomes. They should therefore be read as unadjusted comparisons rather than as documented sponsor-reported inferential analyses.
Analysis population and allocation. The primary outcome description specifies an intent-to-treat analysis set that includes all participants who enrolled. General statistical context: an intent-to-treat approach retains participants in the groups to which they were randomized, regardless of later treatment received, and can preserve the benefits of random allocation when implemented as specified. The registry does not explain how missing primary or secondary outcome observations were handled, whether all randomized participants contributed data to each secondary endpoint, or whether any sensitivity analyses were conducted. Those details are not reported in the registry record.
Planning illustrations. The posted sample-size illustrations use the observed effect as a starting point and consider detecting stated fractions of that effect. Their assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are planning illustrations, not the trial’s original design justification and not observed power. The registry explicitly states that they were computed from the observed effect rather than the trial’s own design. General statistical context: planning calculations ask how many participants might be needed under specified assumptions; they do not show the probability that a completed trial’s result is correct or that a treatment effect exists.
Multiplicity and adaptive design. The trial is described as adaptive, but the adaptation procedures are not reported in the registry record. The record also does not report a multiplicity adjustment or a prespecified hierarchy for the many outcomes. General statistical context: when many outcomes or comparisons are examined, the chance of obtaining at least one apparently notable result by chance can increase. Adjustments or prespecified testing strategies can address that issue, but no such strategy can be inferred from the word adaptive alone. The posted secondary p-values are unadjusted, and their evidential weight should be interpreted accordingly.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies the primary analysis population as intent-to-treat, including all participants who enrolled. It does not report the handling of missing outcome data, the number of participants with missing observations for each endpoint, or any imputation or sensitivity-analysis procedures. The effect of missing data on the posted estimates is therefore not reported in the registry record.
The record lists 19 outcome measures and 18 posted secondary outcomes. It does not report a multiplicity adjustment, a testing hierarchy, or a specific plan for controlling the chance of false-positive findings across secondary comparisons. The mortality p-values are unadjusted. General statistical context: when several outcomes are tested, interpreting each result as though it were the only test can overstate the strength of evidence. A prespecified strategy can help distinguish confirmatory from exploratory analyses, but such a strategy is not reported in the registry record.
The study is described as adaptive, but the adaptation rules, decision points, and effects on the analysis are not reported in the registry record. The label alone does not reveal whether or how enrollment, treatment allocation, or analysis could change during the study. No assumptions about interim analyses or stopping rules can be made from the record.
The primary endpoint is described as using an intent-to-treat set, but corresponding analysis-population details for the secondary outcomes are not reported. The registry also does not state how the posted comparisons account for other prognostic factors, whether any adjusted analyses were conducted, or how deviations from assigned treatment were handled. These omissions limit assessment of the analysis beyond the reported endpoint definition and summary results.
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 |
|---|---|---|---|
| Treatment Protocol | 0 | 252 | 0.0% |
| Control Protocol | 0 | 249 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Protocol | 102 of 252 |
| Control Protocol | 94 of 249 |
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 |
|---|---|
| Treatment Protocol | 2 of 252 |
| Control Protocol | 0 of 249 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Protocol | Control Protocol |
|---|---|---|---|
| Hemorrhagic shock due to hemolysis | Blood and lymphatic system disorders | 1 of 252 | 0 of 249 |
| Worsening of renal function | Renal and urinary disorders | 1 of 252 | 0 of 249 |
The registry’s adverse-event summary lists zero participants with serious adverse events in each group: 0 of 252 in the treatment group and 0 of 249 in the control group. It lists other adverse events for 2 participants in the treatment group and 0 in the control group. These are counts as recorded in the registry; the registry entries do not provide event descriptions for the other adverse events, and no serious adverse-event terms are listed.
The adverse-event summary also lists deaths of 102 participants in the treatment group and 94 in the control group. The registry entries do not specify a timeframe for these death counts within the adverse-event summary, so they should not be assigned a follow-up period on that basis. Mortality at specified follow-up points is reported separately as secondary outcomes.
General statistical context: event counts describe what was recorded, but they do not by themselves establish a causal safety difference between randomized groups. Zero recorded serious events does not show that no serious event could occur, and sparse counts can provide limited precision. Interpretation also depends on the event definitions, observation period, completeness of reporting, and how events were assessed; those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The primary summaries show medians of 25.0 VVFD in the treatment group and 26.0 in the control group, with overlapping interquartile ranges. These summaries describe the observed data but do not provide a formal estimate of the between-group difference. The registry record states that the two-arm comparison was not estimable for this median-time endpoint. Without a reported comparison and its uncertainty, the primary results cannot establish whether the observed medians reflect a meaningful group difference or variation in the study data.
The secondary mortality comparisons also require restraint. Their confidence intervals include no risk difference, and their point estimates do not all point in the same direction. These unadjusted secondary comparisons do not replace the missing primary comparison, and the registry does not report a multiplicity plan. The posted results therefore do not support treating any one secondary estimate as definitive evidence about the full trial question.
General statistical context: an inconclusive estimate is not the same as proof that two interventions are equivalent. Establishing equivalence or non-inferiority requires a prespecified margin and an analysis designed for that purpose; such a margin or analysis is not reported in the registry record. Likewise, a point estimate should not be interpreted as a precise measure of effect when its interval is broad.
The study’s randomized, double-blind, placebo-controlled design can support a structured comparison of assigned protocols, but design features do not remove uncertainty from incomplete or non-estimable results. Open-label corticosteroid use was permitted in the control group under the stated conditions, which is part of the protocol contrast described in the record. Details needed to evaluate adherence, missing outcomes, and the adaptive procedures are not reported in the registry record.
The meaning of the posted findings is therefore bounded: they describe the observed primary distributions, selected mortality counts and comparisons, and recorded adverse-event counts. They do not provide a reported inferential comparison for the primary endpoint, establish equivalence, or resolve the effects of unreported analysis and missing-data procedures.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint’s definition matters as much as its label. VVFD is not simply a count of days without organ support: death receives a zero score, and return to ventilation or vasopressors resets the counter. Those rules create a combined summary of survival and support-free time. Readers need the scoring definition to understand what a group median represents and what kinds of clinical courses it may combine.
It also illustrates the limits of comparing medians without an inferential contrast. The registry posts group medians and interquartile ranges but states that a two-arm comparison was not estimable. A difference between two displayed medians is not, by itself, a treatment-effect estimate with quantified uncertainty. Reporting the reason a comparison is unavailable makes clear that descriptive summaries cannot answer every inferential question.
The trial’s adaptive designation is another statistical detail that requires more than a label. Adaptation rules can affect how a study is conducted and analyzed, but the registry record does not describe them. Without those details, readers cannot assess how adaptation was incorporated into the statistical interpretation. The same principle applies to the trial’s multiple secondary outcomes: without a reported multiplicity strategy, unadjusted comparisons are appropriately treated as supplementary.
Finally, the posted mortality comparisons demonstrate why estimates need to be read alongside their intervals and their endpoint context. A point estimate alone can give an incomplete impression, especially when intervals include no difference and directions vary across outcomes. Together, these features make the trial a useful example of separating descriptive results from inferential conclusions and of identifying where the registry record leaves important statistical details unresolved.
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 most immediate limitation in interpreting the registry results is that the primary endpoint has no reported two-arm comparison. The group medians and interquartile ranges are available, but the record states that values were missing or not estimable for a median-time comparison. No primary confidence interval or p-value is reported, limiting assessment of the precision of the treatment-versus-control contrast.
The record does not report how missing data were handled, the extent of missingness by outcome, or whether sensitivity analyses were performed. It also does not provide numerical results for all secondary measures listed. Consequently, the completeness and robustness of the outcome picture cannot be assessed from the registry record alone.
The study is described as adaptive, but its adaptation procedures are not reported. The registry also does not report a multiplicity plan for the many outcomes, so the posted unadjusted secondary comparisons should be interpreted cautiously. Further statistical details, including any adjusted analyses and the specific procedures used to estimate secondary comparisons, are not reported in the registry record.
The control protocol allowed treating physicians to initiate open-label corticosteroids when indicated under local practice and international guidance. That allowance is part of the stated protocol and may be relevant to how the assigned strategies differed in practice, but the record does not give the frequency of such use. The registry also does not provide detailed adherence information or further participant-level treatment data.
Finally, adverse-event reporting is limited in the registry entries: serious-event counts are zero in both groups, while event terms and additional assessment details are not reported. These registry limitations do not establish that the trial lacked the relevant procedures; they mean only that those details are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Vitamin C, Thiamine, and Steroids in Sepsis — NCT03509350.
- Registry record last updated 2021-04-13; status last verified 2021-03.
- Results first posted 2020-09-18.
- 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
NCT03509350 is the completed VICTAS study, a multicenter, randomized, double-blind, placebo-controlled, adaptive Phase 3 parallel-group trial sponsored by Emory University. It enrolled 501 participants with sepsis. The intervention was intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge; the comparator was matched placebos, with open-label corticosteroids permitted in the control group under the stated conditions.
The primary outcome was VVFD through Day 30, analyzed in an intent-to-treat set including all enrolled participants. The registry posts group medians and interquartile ranges but states that a two-arm comparison was not estimable. Selected mortality outcomes are posted as secondary results, with unadjusted comparisons. Details of missing-data handling, multiplicity, and the adaptive procedures are not reported in the registry record.