The Effect of Thiamine vs. Placebo on VO2 in Critical Illness: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Thiamine vs. Placebo on VO2 in Critical Illness (NCT01985685), a randomized phase 2 study. The primary outcome is Change in VO2 Over Time.

2. Clinical Question

The study also lists metabolic profile as a secondary aim. The registry names percentage change in serum lactate and change in central venous oxygen saturation as secondary outcomes. Those outcomes may describe different aspects of patients’ physiology, but the posted record does not provide their result values in the registry record for this analysis.

The primary question is about a physiological outcome measured after treatment, not a direct comparison of survival or recovery. The posted arm results give median VO2 values of 4.2 for thiamine and 4.3 for placebo, with inter-quartile ranges of 3.7 to 5.7 and 3.5 to 5.3, respectively. These are descriptive summaries. The record does not provide a treatment-effect estimate, confidence interval, or statistical test for the primary outcome, so the medians alone do not establish whether the groups differed beyond the observed summaries.

3. Trial Design

The registry describes a phase 2, randomized, quadruple-masked, parallel-group trial sponsored by Beth Israel Deaconess Medical Center. It is marked completed. The recorded study start is 2013-10 and the primary completion date is 2016-05. Enrollment is recorded as 66.

Participants were assigned to thiamine or placebo. The thiamine arm received a single dose of 200mg intravenous thiamine in 50ml 5% dextrose. The placebo arm received a single dose of 50ml intravenous 5% dextrose. The registry’s masking designation is quadruple, but it does not specify in the available record which roles were masked or how masking was maintained.

The primary outcome is titled “Change in VO2 Over Time.” It is measured in ml/kg/min, uses a median with inter-quartile range, and has a timeframe of 6 hrs. Its description says that change in VO2 over the 6 hours after study medication administration is adjusted for baseline VO2. This indicates a planned focus on post-administration change while accounting for the baseline measure; the record does not provide further details about the adjustment method.

The posted primary outcome summaries list 29 participants for thiamine and 27 for placebo. They are arm-level outcome counts; the registry does not explain the difference between these counts and the recorded enrollment. No statistical analysis results are posted in the record, and the number of analyses is recorded as zero. The registry lists two secondary outcomes: percentage change in serum lactate and change in central venous oxygen saturation. It does not report a detailed statistical plan, allocation procedure, or sample-size justification in the available 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.

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 Change in VO2 Over Time, measured over 6 hrs.

VO2 is oxygen consumption. In this trial, the registry defines the primary endpoint as change in VO2 over the 6 hours after study medication administration, adjusted for baseline VO2. The measure is recorded in ml/kg/min, a scale that expresses oxygen consumption in relation to body weight and time. The registry describes the summary as a median and inter-quartile range.

VO2 is used as a physiological measure of oxygen use. Studying it in critically ill patients requiring mechanical ventilation allows the trial to examine a short-term physiological response to thiamine compared with placebo. A change over time can be informative because it focuses on how the measure behaves after treatment rather than only on a single post-treatment reading. Adjustment for baseline is intended to take the starting VO2 measure into account, although the exact adjustment procedure is not reported in the registry record.

The posted summaries give a median of 4.2 for thiamine, with an inter-quartile range from 3.7 to 5.7, and a median of 4.3 for placebo, with an inter-quartile range from 3.5 to 5.3. The registry does not provide enough detail to determine whether these summaries are adjusted estimates, raw measurements, or a particular calculated change score. It also does not report a between-group estimate or uncertainty interval. Therefore, the values can be described as the posted summaries for the primary outcome, but they should not be interpreted as a complete estimate of the treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial uses a randomized, parallel-group design. In general, random allocation is intended to make treatment groups comparable at the point of assignment, including with respect to both measured and unmeasured factors. It does not guarantee identical groups, especially in a trial of this size, and it does not remove the need to report the actual analysis and its uncertainty. The registry does not describe the randomization sequence or allocation-concealment procedure.

The registry labels the study quadruple-masked. In general, masking can reduce the influence of expectations on care, measurement, and assessment of outcomes. The record does not say which participants, clinicians, investigators, or outcome assessors were masked, or whether masking was tested. The recorded design is parallel, meaning the reported groups represent separate treatment assignments rather than a crossover sequence.

Why report the median and inter-quartile range?

The median is the midpoint of an ordered set of observations: half of the observations lie at or below it and half at or above it, subject to ties. The inter-quartile range describes the middle half of the observed distribution, from the lower quartile to the upper quartile. These summaries can be useful when data are skewed or when a small number of extreme values might pull the mean. They describe the distribution within each arm; they do not directly provide a treatment-effect estimate or its precision.

For the primary outcome, the posted median is 4.2 with an inter-quartile range of 3.7 to 5.7 for thiamine, and 4.3 with an inter-quartile range of 3.5 to 5.3 for placebo. These summaries should be kept distinct from a comparison of the arms. A reader cannot obtain a valid confidence interval or p-value for the treatment contrast simply by comparing medians or observing how much the inter-quartile ranges overlap.

What does baseline adjustment mean?

In general, adjustment for baseline means that the analysis takes the starting value of an outcome into account when estimating the post-treatment result or change. This can help distinguish treatment-group differences from differences that were already present before treatment. The registry says the primary outcome is adjusted for baseline VO2, but does not describe the exact model, how change was calculated, or whether the posted medians are adjusted values. Those details are needed to reproduce or fully interpret an adjusted treatment effect.

Why are uncertainty intervals important?

In general, a confidence interval gives a range of values compatible with the data and the statistical model at a stated confidence level. Its width conveys precision: narrower intervals indicate more precise estimates, while wider intervals indicate greater uncertainty. A confidence interval for the difference between arms would address the treatment contrast directly. The registry record does not report such an estimate or interval for the primary outcome, and does not report a p-value. The arm-level summaries therefore support description, not a complete inferential conclusion.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, standard errors may be too small and uncertainty intervals too narrow. Appropriate model choice and diagnostics matter for outcomes whose distributions do not match simple model assumptions. The registry describes a median and inter-quartile range for VO2 but does not report a model or diagnostics, so there is no basis to determine whether over-dispersion was assessed or relevant to the primary analysis.

What can the sample-size illustrations say?

Any sample-size planning illustration based on an observed effect is a hypothetical planning exercise, not a measure of the trial’s observed power. Such an illustration depends on assumptions about the effect to detect, the significance level, allocation, and statistical approximation. The registry record does not report the trial’s own sample-size justification or the underlying planning assumptions. No planning figures should be treated as evidence that the completed trial had adequate power or that a non-significant result occurred; a primary outcome test is not posted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and two secondary outcomes. The primary outcome is change in VO2 over time; the secondary outcomes are percentage change in serum lactate and change in central venous oxygen saturation. When several outcomes are examined, multiplicity can arise because repeated statistical tests increase the chance of at least one apparently unusual result. In general, a prespecified hierarchy or adjustment can help address this issue. The registry record does not report a multiplicity strategy, testing hierarchy, or statistical plan.

The record lists three outcome measures and zero analyses. It provides the VO2 arm summaries but does not provide results for the two secondary outcomes. It is therefore not possible to assess whether all planned outcomes were analyzed, whether analyses were changed, or how outcome selection affected interpretation. The absence of posted secondary results is not evidence that those outcomes were not measured; their results are simply not reported in the registry record.

Missing-data information is also limited. The primary outcome summaries are associated with 29 participants in the thiamine arm and 27 in the placebo arm, while enrollment is recorded as 66. The registry record does not explain the difference, state reasons for unavailable measurements, or describe any imputation or sensitivity analysis. It does not report the analysis population, such as whether the primary analysis included everyone randomized or only participants with measured outcomes.

In general, missing outcomes can affect interpretation if the likelihood of missingness is related to treatment, health status, or the outcome itself. Without reasons for missingness and a stated analysis approach, the impact cannot be assessed. The posted group summaries should therefore be understood as outcome summaries for the recorded arm counts, not as a documented analysis of every enrolled or randomized participant.

11. 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 registry reports serious adverse events for 29 participants at risk in the thiamine arm and 27 at risk in the placebo arm. The reported number affected is zero in each arm. It also reports zero other adverse events in each arm. These are the posted counts; they do not establish that no events occurred outside the registry’s defined reporting scope or observation period.

The death counts are 9 for thiamine and 5 for placebo. Deaths are reported separately from serious adverse events in the registry data used. The record does not provide the cause of death, timing, follow-up duration, event definitions, or a statistical comparison. The counts alone cannot establish whether treatment caused, prevented, or had no effect on deaths. A safety comparison would require appropriate context, including how events were defined and captured and the uncertainty around any between-group estimate.

In general, a zero count does not prove that an event is impossible or that risk is absent; it means no events were recorded in that category for the reported group and period. The available record does not provide enough detail to judge completeness of safety follow-up or to compare risks with precision. The figures should be read as descriptive registry reports, not as a standalone safety conclusion.

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

The posted results describe a randomized comparison of thiamine and placebo in critically ill patients requiring mechanical ventilation. The primary outcome concerns change in VO2 over the 6 hours after study medication, adjusted for baseline VO2. The recorded median values are 4.2 for thiamine and 4.3 for placebo, with inter-quartile ranges of 3.7 to 5.7 and 3.5 to 5.3. These figures summarize the reported arm-level distributions.

They do not show the estimated treatment effect or its precision. A direct between-group estimate and confidence interval are not reported, and no statistical test is posted. The registry also does not clarify the exact relationship between the baseline-adjusted outcome description and the arm summaries. For those reasons, the values should not be used to claim a statistically supported difference or to conclude that the treatments had equivalent effects.

The two secondary outcomes are named but their values are not reported in the registry record. The adverse-event report gives zero serious and zero other adverse events in each arm, as well as deaths of 9 in the thiamine group and 5 in the placebo group. Those counts lack the context and comparative analysis needed to establish a treatment effect on safety or mortality.

In general, a trial’s results address the population, intervention, comparator, outcomes, and follow-up actually studied. This record concerns a short-term physiological outcome in critically ill, mechanically ventilated patients, and does not provide evidence about longer-term outcomes. The registry record does not report enough detail about eligibility criteria, analysis populations, missing outcomes, or treatment-effect uncertainty to determine how broadly the findings might apply. The appropriate reading is therefore descriptive and limited to the information posted, rather than a clinical recommendation or a claim about efficacy.

13. Why This Trial Matters Statistically

This trial is statistically noteworthy because it pairs a randomized treatment comparison with a physiological endpoint measured over a short post-treatment interval. Randomization can support a fair comparison when implemented and analyzed appropriately, while the baseline-adjusted endpoint description recognizes that participants may start with different VO2 values. The registry does not give enough methodological detail to evaluate the actual adjustment or analysis.

The choice to summarize the primary outcome using medians and inter-quartile ranges communicates the distribution without relying on a mean and standard deviation. That can be useful for data that are asymmetric or contain influential extreme values. But descriptive summaries are not a substitute for a treatment-effect estimate. A clear inferential report would ordinarily identify the contrast, its uncertainty, the analysis population, and the method used to obtain it. Those results are not reported in the registry record.

The difference between recorded enrollment and the arm counts accompanying the primary outcome summaries also illustrates why participant flow and missing-data reporting matter. Without an explanation of the counts or the analysis population, readers cannot tell how the outcome summaries relate to all participants enrolled or assigned to treatment. Similarly, named secondary outcomes without posted results make it difficult to assess the full pattern of planned findings.

Finally, safety counts require context, definitions, follow-up, and uncertainty. The registry’s adverse-event counts are useful as a record of what was reported, but they do not establish comparative safety. These limitations make the trial a useful example of the distinction between a registered question, descriptive outcome summaries, and a complete statistical analysis.

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 main limitation of the posted results is the absence of an inferential comparison for the primary outcome. Although the registry reports medians and inter-quartile ranges by arm, it does not report a treatment-effect estimate, confidence interval, or p-value. The results therefore do not quantify the size or precision of the between-group contrast.

The endpoint description says that change in VO2 over the 6 hours after medication administration is adjusted for baseline VO2, but the registry does not explain the adjustment method or how the reported arm summaries correspond to that description. A statistical model, analysis details, and definitions of the calculated change would be needed to interpret the adjusted outcome fully.

The primary outcome counts are 29 for thiamine and 27 for placebo, while enrollment is recorded as 66. The registry does not explain the discrepancy, describe participant flow, give reasons for missing outcomes, or specify the analysis population. It also does not report methods for handling missing data or sensitivity analyses. These omissions limit assessment of whether the posted results could be affected by incomplete outcome data.

The registry names two secondary outcomes but does not report their values. It does not state whether the outcomes were analyzed according to a prespecified hierarchy or whether multiplicity was addressed. Detailed eligibility criteria, allocation procedures, masking roles, and a statistical analysis plan are not available in the record. The record also does not report the trial’s sample-size justification.

Safety information is limited to counts. Definitions, event timing, follow-up duration, causes of death, and comparative analyses are not reported. These limitations prevent a complete interpretation of the trial’s efficacy and safety results from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effect of Thiamine vs. Placebo on VO2 in Critical Illness — NCT01985685.
• Registry record last updated 2017-10-02; status last verified 2017-09.
• Results first posted 2017-10-02.
• 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.

18. Record Summary

NCT01985685 is a completed phase 2 randomized, quadruple-masked, parallel-group trial sponsored by Beth Israel Deaconess Medical Center. The registry records enrollment of 66 and compares a single intravenous dose of 200mg thiamine in 50ml 5% dextrose with a single intravenous dose of 50ml 5% dextrose as placebo.

The primary outcome is change in VO2 over time, described as baseline-adjusted over the 6 hours after study medication. The posted medians are 4.2 for thiamine and 4.3 for placebo, with inter-quartile ranges of 3.7 to 5.7 and 3.5 to 5.3. No primary-outcome statistical comparison is reported. Two secondary outcomes are listed, but their results are not reported in the registry record.

The safety record reports zero serious and zero other adverse events in each arm, with deaths of 9 and 5, respectively. The available registry information does not provide the context or analysis needed to interpret these counts as treatment effects.