GR270773 In The Treatment Of Suspected Or Confirmed Gram-Negative Severe Sepsis In Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for GR270773 In The Treatment Of Suspected Or Confirmed Gram-Negative Severe Sepsis In Adults (NCT00089986), a randomized phase 2 study. The primary outcome is Percentage of Participants With 28-Day All Cause Mortality.

2. Clinical Question

The question is specific to short-term all-cause mortality in this study population and to the treatment regimens tested. It is not a general comparison of all treatments for sepsis, nor does it address outcomes beyond the registry’s stated follow-up. The primary endpoint counted deaths between days 1 and 28. Participants who withdrew from the study and whose survival at day 28 could not be confirmed were treated as deaths for that endpoint.

The trial also collected information on new organ failure and safety. Those outcomes may help describe the broader pattern of events during follow-up, but they are secondary to the mortality question. The registry record does not report the actual dose levels, detailed eligibility criteria, or a more specific description of the intended Gram-negative infection confirmation process.

3. Trial Design

This was a randomized, parallel-group, double-blind, placebo-controlled, dose-ranging phase 2 study. It was described as prospective and multicenter. Participants were assigned to placebo, low-dose GR270773, or high-dose GR270773. GR270773 was administered as a three-day continuous intravenous infusion. The record identifies adults with suspected or confirmed Gram-negative severe sepsis as the intended population.

The registry reports enrollment of 1415. The primary outcome results list 599 participants for placebo, 598 for low-dose GR270773, and 182 for high-dose GR270773. The record does not explain the relationship between the overall enrollment figure and the group sizes shown with the primary outcome, or why group sizes differ. The randomized sequence-generation and allocation-concealment procedures are not reported in the registry record.

The primary outcome was percentage of participants with 28-day all-cause mortality, assessed from day 1 after infusion through day 28 follow-up. The registry describes the primary objective as estimating the effect of two doses versus placebo. Its stated primary analysis population includes randomized participants from all three stages who received any study drug; how participants who were randomized but received no study drug were handled is not reported in the registry record.

Secondary outcomes included new onset organ failure in an organ not in failure at enrollment, specified types of new organ failure, and adverse events, serious adverse events, and fatal serious adverse events. The registry record also reports counts for serious and other adverse events. Details of treatment adherence, co-interventions, site-level variation, and the trial’s original sample-size justification 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: A total of 1415 participant numbers were assigned during randomization process, five were duplicate randomization numbers and for other two, the participants did not provide informed consent, precluding them from enrollment. Out of 1408 participants, 29 did not receive study medication, remaining 1379 included in Intent-to-Treat (ITT) Population.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population was defined as all randomized participants from all three stages who receive any study drug.

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 Percentage of Participants With 28-Day All Cause Mortality, measured over Day 1 (post-infusion) up to Day 28 Follow-up.

The primary endpoint was the percentage of participants with all-cause mortality between day 1 and day 28. It counts death regardless of the attributed cause, so it gives a direct measure of short-term survival without requiring a judgment that death was caused by sepsis or by study treatment. The registry also describes recording details such as cause of death, source of information, and whether a death record verified the cause.

For this endpoint, participants who withdrew from the study and for whom survival at day 28 could not be confirmed were treated as deaths. This rule makes the endpoint definition explicit for that circumstance, although the number of participants handled this way is not reported in the registry record. The registry defines the analysis population as randomized participants from all three stages who received any study drug.

All-cause mortality is clinically consequential and relatively straightforward to interpret as an outcome, but a single endpoint does not describe the full course of severe sepsis. It does not by itself show the timing or cause of death, the severity of nonfatal illness, or the burden of organ failure. Those topics are partly addressed by secondary outcomes, but their results should not be treated as interchangeable with the primary mortality endpoint. The registry record does not report additional endpoint-adjudication procedures beyond the description of death details.

7. Results Posted in the Registry

• Low GR270773: 25.8% (154/598) versus 26.9% (161/599) on control; risk difference -1.1 percentage points (95% CI -6.1 to 3.9), risk ratio 0.96 (0.79–1.16); unadjusted two-proportion z-test p = 0.658.
• High GR270773: 31.3% (57/182) versus 26.9% (161/599) on control; risk difference 4.4 percentage points (95% CI -3.2 to 12.1), risk ratio 1.17 (0.91–1.50); unadjusted two-proportion z-test p = 0.242.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With New Onset Organ Failure, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrolment

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Low GR270773: 26.3% (157/598) versus 20.4% (122/599) on control; risk difference 5.9 percentage points (95% CI 1.1 to 10.7), risk ratio 1.29 (1.05–1.59); unadjusted two-proportion z-test p = 0.016.
  • High GR270773: 31.3% (57/182) versus 20.4% (122/599) on control; risk difference 11.0 percentage points (95% CI 3.5 to 18.4), risk ratio 1.54 (1.18–2.01); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Low GR270773 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for High GR270773 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry identifies secondary questions about new organ failure, specified forms of organ failure, and adverse events. The quantitative secondary results include new onset organ failure in an organ that was not in failure at enrollment. The posted pattern for that outcome differs from the primary mortality pattern: the event counts are higher in both GR270773 groups than in the placebo group, and the recalculated risk differences are positive. The record also contains serious and other adverse-event counts. These outcomes add context about events observed during follow-up, but they do not replace the primary mortality comparison.

Secondary endpoints can help describe possible pathways or broader consequences that a mortality measure alone cannot capture. However, they may be defined and analyzed differently, and they do not necessarily measure the same aspect of illness. New organ failure is not equivalent to death; a participant can experience organ failure without dying, and mortality can occur without the particular secondary event being recorded. The registry’s listed endpoint definitions should be considered separately rather than combined into a single overall judgment.

Unadjusted secondary comparisons carry less weight when many outcomes or group comparisons are examined. General statistical explanation: looking at multiple outcomes creates more opportunities for an apparently unusual result to occur by chance, even if no underlying effect exists. A prespecified multiplicity strategy can address that issue, but such a strategy is not reported in the registry record. The secondary results should therefore be treated as descriptive or hypothesis-generating, not as confirmatory evidence that overrides the primary endpoint.

The posted secondary pattern does not establish a mechanism for the mortality findings. Nor does the registry record report enough information to determine whether all planned secondary endpoints were analyzed or how missing observations were handled for each one. These limitations make it important to distinguish what the trial measured from what can be concluded about treatment effects.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With New Onset Organ Failure, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrolment
• Number of Participants With New Onset Organ Failure of Respiratory Failure, Cardiovascular Failure, Renal Failure and Coagulopathy, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrollment
• Assessment of Safety/Tolerability by Determining the Number of Participants With Any Adverse Events (AE), Serious Adverse Events (SAE) and Fatal SAE

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a binary primary outcome: whether a participant died during the specified follow-up. For a binary outcome, a group’s event proportion describes how often the event occurred among participants in that group. The posted mortality percentages are such group summaries. They are useful for seeing the observed event frequency, but a comparison of percentages needs an uncertainty estimate because results from a trial can vary across samples.

What does a risk difference describe?

General statistical explanation: a risk difference subtracts one group’s event proportion from another group’s event proportion. The recalculated comparisons use treatment minus placebo, so a negative estimate corresponds to a lower observed event proportion in the treatment group, while a positive estimate corresponds to a higher observed event proportion. These are unadjusted comparisons of the posted summary counts, not model-adjusted treatment effects. For low dose the estimate is -0.011; for high dose it is 0.044.

The registry’s own analysis reports rate differences using placebo minus treatment, as specified in the primary endpoint description. Reversing the order of subtraction reverses the sign, but does not change the underlying group data. The registry reports the low-dose difference as 1.1 and the high-dose difference as -4.4. Because its reported analyses and the recalculations use different subtraction conventions and confidence-interval levels, the two sets of figures should not be compared without accounting for those differences.

What does a confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimate under a statistical procedure. A wider interval means the estimate is less precise; a narrower interval means it is more precise. An interval that includes no difference does not prove that the groups are the same. It means the data and method do not rule out no difference at the interval’s stated confidence level. The recalculated 95% intervals for both mortality comparisons include no difference and values in either direction.

The registry reports 90% confidence intervals for its own comparisons, but only the lower bound is reported for each; the upper bound is not reported. That makes the registry’s interval information incomplete in the posted analysis. The recalculated intervals are not a substitute for the sponsor’s analysis, and their 95% level differs from the registry’s stated 90% level.

How should p-values be understood?

General statistical explanation: a p-value describes how unusual data at least as discrepant as those observed would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The recalculated unadjusted p-values are 0.658 for low dose and 0.242 for high dose. The sponsor reports 0.329 and 0.879, respectively, using its own analysis. These values should be interpreted alongside the estimated differences and intervals, not on their own.

The registry labels the sponsor’s method as Chi-squared and its parameter as rate difference. A chi-squared procedure is a method for comparing categorical outcome data. The exact details of the sponsor’s calculation, including any additional adjustments or implementation choices, are not reported in the registry record. The recalculations use posted group counts and are unadjusted; they should therefore be understood as a separate descriptive check rather than a reconstruction of every part of the sponsor’s analysis.

Why does group size matter?

General statistical explanation: estimates from groups with fewer participants are often less precise when other features are similar, because there is less information about the event frequency. The high-dose group has fewer listed participants than either the placebo or low-dose group. Its mortality estimate consequently has a wider recalculated interval than the low-dose comparison. The pattern is also affected by how often the event occurs and by the design and analysis methods; group size alone does not determine precision.

Randomization is intended to support a fair comparison by assigning participants to groups, while blinding can reduce some forms of bias in care or outcome assessment. The registry identifies the study as randomized and double blind, but the methods used for sequence generation, allocation concealment, and maintenance of blinding are not reported in the registry record. The record also does not report a detailed statistical analysis plan, adjustment for baseline variables, handling of multiple comparisons, or interim-analysis procedures. Those details should not be inferred from the trial design label.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data locate the treatment effect, not whether a result is important. The recalculated low-dose risk difference is -0.011, with a 95% confidence interval from -0.061 to 0.039. The interval includes no difference and permits effects in either direction. The point estimate is close to zero, but the interval does not pin the effect down to a narrow range around that estimate.

The high-dose risk difference is 0.044, with a 95% confidence interval from -0.032 to 0.121. This interval also includes no difference and values on both sides of it. Its range is wider than the low-dose interval, consistent with less precise estimation for the high-dose comparison, which has a smaller listed group size. Neither interval establishes equivalence or excludes all potentially meaningful differences.

The sponsor’s analyses report 90% confidence intervals but only the lower bounds: -2.1 for low dose and -9.4 for high dose. The upper bounds are not reported in the registry record. These partial intervals cannot show the full uncertainty range. The sponsor’s rate differences are reported as placebo minus treatment, unlike the recalculations, which use treatment minus placebo.

General statistical explanation: intervals are affected by the number of observations, event frequency, allocation, and the analysis method. The reported figures cannot be interpreted as a guarantee that the true effect lies within a particular range for this trial. They are uncertainty summaries under their respective statistical procedures. The registry record does not report a clinical threshold that would distinguish a meaningful effect from a trivial one, so precision alone cannot resolve clinical importance.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size display is a planning illustration based on the observed effect, not the trial’s original design calculation. Its assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculation considers detecting the stated fraction of the observed effect. The registry’s original sample-size assumptions and justification are not reported in the registry record.

For these binary outcomes, the figures are participants per arm, not total participants. The 80% power column gives the planned number of participants per arm under which the calculation has an 80% chance of detecting the selected effect, if the assumptions and effect are correct. The 90% power column expresses the corresponding planning target for a higher chance of detection. These are design concepts; neither column describes what happened in the completed trial.

The rows describe planning for 100%, 75%, or 50% of the observed effect. A smaller effect is harder to distinguish from random variation, so it requires more participants per arm under the same assumptions. That relationship is why the planning figures increase as the assumed effect becomes a smaller fraction of the observed one.

These figures are not observed power. They are hypothetical planning estimates based on the observed effect, and the observed effect itself is uncertain. If the true effect differed from the observed estimate, or if the actual design assumptions differed from the illustration, the required sample size could also differ. The display should therefore be read as a sensitivity illustration, not as evidence that the completed trial was adequately or inadequately powered under its original plan.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.269; treatment proportion p₁ = 0.258; average p̄ = 0.263.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6227 = 1.2206.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6227 = 0.5241.
4. n = (1.2206 + 0.5241)² / (-0.0113)² = 24,022.4, rounded up to 24,023 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.268781302170284                          # control proportion
p1 <- 0.25752508361204                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(89986)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 24,023 (80% power), 32,159 (90% power)
 75% of observed effect: n per arm = 42,854 (80% power), 57,369 (90% power)
 50% of observed effect: n per arm = 96,750 (80% power), 129,521 (90% power)
power.prop.test: 24022.4 
Simulated power at n = 24,023 per arm: 0.798 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s own primary analyses compare placebo with each dose using Chi-squared methods and report rate differences. The endpoint description defines those differences as placebo minus treatment. The reported low-dose difference is 1.1, with a reported p-value of 0.329; the reported high-dose difference is -4.4, with a reported p-value of 0.879. Each reported 90% confidence interval has a lower bound, but its upper bound is not reported.

The unadjusted recalculations use treatment minus placebo and report risk differences of -0.011 for low dose and 0.044 for high dose, with 95% confidence intervals and unadjusted p-values. The opposite subtraction direction explains the difference in sign convention. The interval levels also differ, and the registry’s reported interval limits are incomplete. The recalculations are based on the posted summary statistics and should not be treated as identical to the sponsor’s analysis.

The sponsor’s own analysis takes precedence as the trial’s reported analysis. The record does not report enough detail to establish every analytic choice behind that analysis, including whether anything beyond the named method was applied. Neither the sponsor-reported p-values nor the recalculated ones show a clear mortality difference. Interpretation should prioritize the effect estimates and their uncertainty rather than selecting one p-value as a definitive verdict.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint description gives a specific rule for participants who withdrew and whose survival at day 28 could not be confirmed: they were treated as deaths. The registry does not report how many participants were subject to this rule, whether other missing primary-outcome information occurred, or how missing values were handled in other outcomes. It also does not report sensitivity analyses that might show how alternative assumptions about missing outcomes affect the results.

The stated primary analysis population is the ITT Population, defined as all randomized participants from all three stages who received any study drug. That definition does not include randomized participants who received no study drug. The number of such participants, if any, and their handling in the analyses are not reported in the registry record. The acronym should therefore be interpreted using the registry’s stated definition rather than assuming a different population convention.

The trial includes two dose comparisons against placebo and multiple secondary outcomes. When several comparisons are assessed, the chance of at least one apparently notable result can increase. General statistical explanation: multiplicity procedures can control that risk, for example by adjusting inference across a defined family of tests. Whether the trial used a prespecified adjustment, a hierarchical testing plan, or another strategy is not reported in the registry record. The posted recalculated p-values are explicitly unadjusted.

Interim analyses, stopping rules, and any changes to the analysis plan are not reported in the registry record. The detailed statistical analysis plan is also not reported, so it is not possible to establish from this record which comparisons were designated confirmatory or how the analysis addressed all endpoints. These omissions do not prove that such procedures were absent; they mean the registry record does not document them. As a result, secondary findings and multiple dose comparisons warrant cautious interpretation, especially when considered individually.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: metabolic acidosis (12.6%), cardiac arrest (9.3%), hepatic failure (8.2%), mental impairment (6.6%), hypoglycaemia (1.7%).

The registry reports serious adverse events in 213 participants in the placebo group, 235 in the low-dose group, and 77 in the high-dose group. It reports other adverse events in 160, 183, and 60 participants, respectively, and deaths in 85, 70, and 33 participants, respectively. The corresponding groups at risk are listed as 599, 598, and 182. These are counts, not adjusted comparisons, and group sizes differ.

Metabolic acidosis, cardiac arrest, hepatic failure, mental impairment, hypoglycaemia, and increased lipase are among the listed serious adverse-event terms, with their reported percentages. The registry record does not provide enough detail in these figures to establish event timing, severity beyond the serious classification, causal attribution, or comparative risk adjusted for follow-up or baseline characteristics. A serious adverse event is not necessarily caused by study treatment.

These counts describe safety events recorded during the study, but they do not by themselves establish whether one regimen is safer. The registry’s specified safety outcome includes adverse events, serious adverse events, and fatal serious adverse events; the methods for coding, adjudication, and assessing relatedness are not reported in the registry record. The numerical pattern should be interpreted in light of the differing group sizes and the clinical severity of the underlying illness.

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

The trial provides randomized comparisons of placebo with low-dose and high-dose GR270773 in adults with suspected or confirmed Gram-negative severe sepsis. Its primary endpoint was all-cause mortality through day 28. The posted group percentages describe the observed mortality in each arm, while the recalculated differences and confidence intervals indicate substantial uncertainty about the size and direction of the comparisons.

The low-dose mortality percentage was close to the placebo percentage. The high-dose mortality percentage was higher than the placebo percentage. Neither recalculated confidence interval excludes no difference, and the sponsor’s own reported analyses do not provide evidence of a clear difference in mortality. This does not establish that the treatments are equivalent, that any possible effect is clinically unimportant, or that a difference in either direction is impossible.

The findings apply to the trial population, regimens, and follow-up described in the registry record. The actual dose amounts are not reported in the registry record, and the record does not provide the detailed eligibility criteria needed to characterize the participants more fully. Results should not be extended automatically to other populations, doses, settings, or durations of treatment.

The secondary organ-failure and adverse-event information can add context, but it does not resolve the uncertainty in the mortality comparison. Multiple secondary outcomes also make isolated unadjusted findings less conclusive. The registry record does not report a multiplicity strategy, detailed missing-data analyses, or the full statistical plan. Taken together, the posted data are best read as a description of observed outcomes with uncertain treatment-effect estimates, rather than as a definitive demonstration of benefit or harm.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment-effect estimate should be read together with its uncertainty. The observed mortality percentages are easy to compare, but the confidence intervals show that the data do not locate the effect precisely enough to rule out no difference for either dose. A point estimate alone can create a stronger impression than the full range of plausible values supported by the analysis.

It also illustrates the importance of knowing the contrast direction. The registry defines its rate difference as placebo minus treatment, while the recalculated risk differences use treatment minus placebo. The signs therefore point in opposite directions for the same underlying comparison. Clear labeling of the groups, outcome, and subtraction convention is essential for avoiding an erroneous interpretation.

The unequal listed group sizes, particularly the smaller high-dose group, help explain why precision differs across comparisons. Dose-ranging studies can provide information about more than one regimen, but the resulting multiple comparisons need careful interpretation. The registry record does not report the multiplicity plan or the original sample-size assumptions, so the posted planning illustrations should not be confused with the trial’s design rationale.

Finally, a nonsignificant result is not proof of no effect, and an observed difference is not proof of a causal effect by itself. The estimates, confidence intervals, design, endpoint definitions, analysis population, and reporting completeness all matter. This example makes those distinctions especially important when the endpoint is serious, the group sizes are uneven, and secondary outcomes are also available.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the actual GR270773 dose levels, detailed eligibility criteria, randomization sequence-generation method, allocation-concealment procedure, or operational details of blinding. It also does not explain why the group sizes reported for the primary outcome differ, or how those outcome groups relate to the reported enrollment of 1415. These gaps limit assessment of the trial’s conduct and population.

The sponsor’s primary analyses report only lower confidence-interval bounds; the upper bounds are not reported in the registry record. The recalculations provide unadjusted 95% intervals from posted summary statistics, but they do not reproduce all details of the sponsor’s analysis. The registry does not provide a full statistical analysis plan, original sample-size assumptions, interim-analysis information, or a stated multiplicity strategy.

Missing-data handling is described for participants whose day-28 survival could not be confirmed after withdrawal, but the number affected and the handling of missing data elsewhere are not reported. The registry’s analysis-population definition includes randomized participants who received study drug; details about randomized participants who did not receive study drug are not reported.

Follow-up for the primary outcome ends at day 28, so these results do not describe longer-term mortality or other later outcomes. The record also does not provide enough information to assess baseline comparability, treatment adherence, co-interventions, site-level differences, or the adjudication and causal attribution of safety events. These are limitations of what can be evaluated from the registry record and do not establish that the trial lacked those procedures or data.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: GR270773 In The Treatment Of Suspected Or Confirmed Gram-Negative Severe Sepsis In Adults — NCT00089986.
• Registry record last updated 2017-08-21; status last verified 2017-07.
• Results first posted 2017-05-04.
• 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.

23. Record Summary

NCT00089986 is a completed randomized, parallel-group, double-blind, placebo-controlled phase 2 dose-ranging trial sponsored by GlaxoSmithKline. It studied a three-day continuous intravenous infusion of GR270773 in adults with suspected or confirmed Gram-negative severe sepsis. The registry reports enrollment of 1415.

The primary outcome was percentage of participants with all-cause mortality from day 1 through day 28. The posted mortality percentages were 26.9% for placebo, 25.8% for low-dose GR270773, and 31.3% for high-dose GR270773. Recalculated unadjusted risk differences have confidence intervals that include no difference. The registry’s own reported analyses use a different subtraction direction and include incomplete confidence-interval reporting.

Secondary outcomes addressed new organ failure and safety. The registry record does not report the full statistical plan, multiplicity approach, original sample-size rationale, or several trial-conduct details. The posted results describe observed outcomes, but they do not establish a clear mortality effect for either dose.