Reevaluation Of Systemic Early Neuromuscular Blockade: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reevaluation Of Systemic Early Neuromuscular Blockade (NCT02509078), a randomized phase 3 study. The primary outcome is Hospital Mortality to Day 90.

2. Clinical Question

In statistical terms, the trial compares two assigned care strategies, rather than isolating the effect of drug exposure among only those who received it. That distinction matters because the control strategy discouraged non-study neuromuscular blockers rather than stating that they could never be used. The registry record does not report how often the strategies were followed or whether participants switched treatment. Nor does it provide enough endpoint data to determine the direction, size, or precision of any treatment contrast.

3. Trial Design

This was a phase 3, randomized, parallel-group trial with no masking. The sponsor was Massachusetts General Hospital. The registry record lists enrollment of 1008, a start date of 2016-01-04, primary completion on 2018-07-03, and status as completed. Further detail about the randomization procedure, allocation concealment, or trial conduct is not reported in the registry record.

The intervention arm was called Early Neuromuscular Blockade (NMB). Its description says participants received cisatracurium besylate for the first 48 hours of the trial. The comparator, Control: No Routine Early NMB, discouraged use of non-study neuromuscular blockers. Because masking was listed as none, the trial was open label: participants and care teams were not masked to assigned strategy, according to the registry’s design classification. The record does not describe any steps used to limit the influence of knowing the assignment.

The primary endpoint was labeled Hospital Mortality to Day 90. The listed secondary outcomes include ventilator-free days, organ-failure-free days, intensive-care-unit-free days, hospital-free days, measures of daily living, health-related quality of life, post-traumatic stress-like symptoms, and cognitive assessment. The registry lists 16 outcome measures and 1 analysis, but does not provide a complete analysis plan or explain how the outcome measures relate to that analysis count. The registry record does not report the planned sample-size justification, detailed eligibility criteria, or whether interim analyses were planned.

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

Reasons for not completing this period:

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 Hospital Mortality to Day 90, measured over 90 days after randomization.

The primary endpoint is labeled Hospital Mortality to Day 90. Its description defines the measure as the percentage of participants alive at study day 90 and specifies that participants discharged home before day 90 count as alive at day 90. Thus, the stated endpoint is based on survival status at a fixed follow-up point, with an explicit rule for people who leave hospital earlier.

Survival at a specified time is used in clinical trials because it gives a clinically meaningful status that can be compared across assigned groups. In general, a fixed-time outcome can be expressed as the proportion alive by that point, while a mortality label describes the same status from the perspective of deaths. The registry’s wording contains both labels: the outcome title refers to hospital mortality, while the description gives the percentage alive. The record does not report how the endpoint was operationalized in the statistical analysis or how any missing day-90 status was handled.

No arm-specific percentage, event count for this endpoint, effect estimate, confidence interval, or significance test is reported in the registry record. The posted material therefore does not establish the size or precision of a difference between the strategies for this primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is a design method intended to make assigned groups comparable, on average, with respect to measured and unmeasured participant characteristics. It supports a causal comparison of assignment strategies when the trial is conducted and analyzed appropriately. It does not guarantee that the groups will be identical, and it does not replace reporting baseline characteristics, adherence, losses to follow-up, and the analysis used. The registry record identifies the trial as randomized, but details of the sequence generation and allocation procedures are not reported in the registry record.

A parallel-group design assigns participants to a strategy that is compared with another strategy. Here, the named strategies were early cisatracurium besylate and a control approach discouraging routine early neuromuscular blockade. In general, the effect of assignment can differ from the effect of actually receiving treatment if there is nonadherence or use of treatments outside the assigned strategy. The registry descriptions establish the intended approaches, but adherence and crossover information are not reported in the registry record.

The record classifies masking as none. In general, open-label treatment knowledge can influence behavior, co-interventions, outcome assessment, or reporting, especially for outcomes that involve judgment or self-report. A survival status endpoint may be less subjective than a rating scale, but the registry record does not describe outcome adjudication or safeguards against assessment bias. The secondary outcomes include measures such as quality of life, daily functioning, symptoms, and cognition; details of their assessment and masking are not reported in the registry record.

The endpoint description uses survival status at a fixed follow-up time. A group-level proportion alive can be compared with the corresponding proportion in another group, but the registry record does not give those proportions or the chosen effect scale. Different scales answer different questions: a difference in proportions expresses an absolute contrast, while a ratio expresses a relative contrast. These are general statistical distinctions, not reported analyses for this trial. No specific primary-outcome effect measure is reported in the registry record.

For binary outcomes, a confidence interval communicates uncertainty around an estimated group contrast. It reflects both the amount of information in the data and the statistical model used. A p-value, when reported, assesses compatibility between the data and a null hypothesis under specified assumptions; it does not state the probability that the null hypothesis is true or measure clinical importance. The primary estimate, confidence interval, and p-value are not reported in the registry record, so these methods cannot be used to characterize the trial’s primary result.

The registry lists a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Such an illustration asks, in general, how many participants per arm might be needed to detect an assumed effect under stated conditions. It is not observed power, does not show the trial’s actual power, and is not the trial’s original sample-size justification. The record does not report the trial’s own sample-size rationale. The primary outcome’s multiple categories or time points also mean that a single observed effect for a planning calculation is not described as a direct primary comparison in the registry record.

Over-dispersion is a general issue when event counts vary more than a simple statistical model expects. If present and ignored, uncertainty estimates can be too small. The primary endpoint is characterized as a participant count and the record does not give a dispersion estimate or identify an over-dispersed model; therefore no such modeling detail can be inferred. This is distinct from the listed planning illustration, which specifies a normal approximation.

Multiplicity arises when several outcomes or comparisons are examined. In general, more testing creates more opportunities for a chance finding, so researchers may define a hierarchy or adjust inference. The record lists 16 outcome measures and 1 analysis, but does not report a multiplicity procedure, hierarchy, or explanation of the analysis count. It is therefore not possible to determine how the various outcomes were handled inferentially. These are general considerations for interpreting the design and reported material, not claims about unreported procedures in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 16 outcome measures, including the primary survival endpoint and secondary measures covering days free of ventilation, organ failure, intensive care, or hospitalization, as well as functioning, quality of life, symptoms, and cognition. It also lists 1 analysis. The record does not explain whether that count refers to a particular analysis set, an outcome, or another registry convention. A multiplicity adjustment, outcome hierarchy, or prespecified testing sequence is not reported in the registry record.

Multiplicity matters because repeated testing across several outcomes can increase the chance of a nominally unusual result even when there is no underlying effect. General approaches include defining a primary hypothesis in advance, controlling an overall error rate, or treating secondary findings as exploratory. The registry information does not establish which approach, if any, was used. Since the primary result is not reported as a single comparison, the outcome-level evidence cannot be reconstructed from the record.

Missing-data procedures are not reported in the registry record. The endpoint description states that participants discharged home before day 90 were counted as alive, but does not explain how other unavailable day-90 statuses were treated. The analysis population is also not reported: the record does not specify whether analyses followed assignment regardless of treatment received, included only participants who followed the assigned strategy, or used another population definition. These details affect the interpretation of a randomized comparison. No assumptions about missingness, imputation, exclusions, or sensitivity analyses can be inferred from the available registry information.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac arrest (1.2%), pneumothorax (1.0%), stroke (0.6%), ventricular tachycardia (0.4%), pneumomediastinum (0.4%).

For Early Neuromuscular Blockade (NMB), the registry lists 28 participants with serious adverse events among 501 at risk, and 19 with other adverse events among 501 at risk. For Control: No Routine Early NMB, it lists 21 participants with serious adverse events among 505 at risk, and 15 with other adverse events among 505 at risk. These are recorded participant counts, not rates calculated for this analysis. The registry does not explain whether participants could contribute to both serious and other adverse-event categories, so the counts should not be added or treated as mutually exclusive.

The top serious-event terms listed are Cardiac Arrest at 1.2%, Pneumothorax at 1.0%, Stroke at 0.6%, Ventricular Tachycardia at 0.4%, Pneumomediastinum at 0.4%, and Methemoglobinemia at 0.2%. The denominator and calculation details for these percentages are not reported in the registry record. They should be read as entries in the registry’s serious-event listing, not as a direct comparison between randomized groups.

The record also lists 213 deaths in the early-blockade group and 216 in the control group, but the timing and definition attached to these safety-field counts are not reported there. They cannot be substituted for the day-90 primary endpoint. Differences in adverse-event counts alone do not establish causation, and the registry record does not provide the context needed to assess event timing, severity by group, or attribution.

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

The trial’s stated aim was to evaluate whether early neuromuscular blockade with cisatracurium besylate affected survival among people with acute respiratory distress syndrome. The comparator was a strategy in which routine early use of non-study neuromuscular blockers was discouraged. The trial was randomized, parallel-group, phase 3, and open label, with registry enrollment of 1008.

The primary endpoint description defines survival status at day 90 and counts participants discharged home before that time as alive. However, the registry record does not report a single result for this endpoint. There is no arm-specific percentage alive, no direct effect estimate, and no confidence interval or p-value to show the magnitude and precision of a comparison. The record therefore does not support a conclusion that either strategy improved survival, worsened survival, or had no effect.

Nor does the lack of a reported comparison establish that the strategies were equivalent. Equivalence or non-inferiority requires a specified margin and an analysis designed to assess that question; these are not reported in the registry record. A non-significant test, if one existed, would not by itself show equivalence, and no such test result is reported.

The serious adverse-event entries provide a descriptive safety record, but they do not resolve the primary efficacy question. Their group counts and listed event terms lack information on timing, attribution, and detailed analysis. Secondary outcomes are named, but their results are not reported in the registry record. The appropriate interpretation is therefore narrow: the record describes the question and design, while the comparative clinical findings and their uncertainty remain unavailable.

13. Why This Trial Matters Statistically

This trial raises a clear statistical comparison: assignment to early cisatracurium besylate versus a control strategy discouraging routine early neuromuscular blockade, with survival at day 90 as the stated primary endpoint. Randomization is relevant because it is designed to support a fair comparison of assigned strategies. The open-label design, however, makes transparent reporting of adherence, co-interventions, outcome ascertainment, and analysis especially useful for interpreting results.

The endpoint wording also illustrates why outcome definitions matter. The title refers to hospital mortality, while the description specifies the percentage alive at day 90 and treats participants discharged home earlier as alive. That description helps clarify the intended status measure, but the absence of an arm-level result prevents assessment of the comparative effect. A well-defined endpoint is necessary for interpretation, but it is not a substitute for reporting the estimate and its uncertainty.

The breadth of the listed secondary outcomes creates another statistical consideration. Measures of survival, days free of clinical states, functioning, quality of life, symptoms, and cognition may address different dimensions of outcome. Multiple endpoints can be valuable, but interpretation depends on knowing which questions were prioritized and how multiplicity was handled. Those details are not reported in the registry record.

Finally, planning assumptions should not be confused with observed evidence. A sample-size illustration based on an assumed fraction of an observed effect is a planning exercise, not a finding and not the trial’s actual design justification. The record’s limited analysis detail and absent primary comparison mean that the central statistical question remains unresolved in the posted results. This is an important distinction between knowing that a trial was conducted and being able to evaluate what its outcome data show.

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 primary limitation for interpreting this trial from the registry record is the absence of a single reported primary-outcome comparison. The record states that the primary outcome has several categories or time points and was not reduced to one comparison. It gives no arm-specific day-90 survival values, effect estimate, confidence interval, or test result. The comparative result and its precision are therefore not assessable.

The endpoint title and description use different framings: “Hospital Mortality to Day 90” is titled as mortality, while the description defines the measure as the percentage alive. The rule for counting people discharged home is stated, but the record does not report the handling of other missing day-90 status or the detailed analysis definition. These gaps limit reproducibility and interpretation.

Important design and analysis details are also absent. The registry record does not report detailed eligibility criteria, baseline characteristics, randomization procedures, allocation concealment, adherence, crossover, co-interventions, analysis populations, missing-data methods, multiplicity handling, or the trial’s sample-size justification. It classifies the trial as open label but does not describe protections against assessment bias. These items cannot be assumed from the design label.

The safety entries are limited by missing context about event timing, attribution, denominators for the listed serious-event percentages, and overlap among event categories. The recorded death counts are not tied in that field to the day-90 endpoint definition. The registry lists secondary outcomes, but their results are not reported in the registry record. These limitations are specific to what the record documents; they do not establish that the underlying trial lacked procedures or analyses that are not described there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Reevaluation Of Systemic Early Neuromuscular Blockade — NCT02509078.
• Registry record last updated 2019-08-13; status last verified 2019-07.
• Results first posted 2019-08-13.
• 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

The registry record describes NCT02509078, Reevaluation Of Systemic Early Neuromuscular Blockade, a completed phase 3 randomized parallel-group trial sponsored by Massachusetts General Hospital. It lists enrollment of 1008, no masking, a start date of 2016-01-04, and primary completion on 2018-07-03. The condition was acute respiratory distress syndrome.

The intervention was cisatracurium besylate for the first 48 hours; the control strategy discouraged routine early use of non-study neuromuscular blockers. The primary endpoint was labeled Hospital Mortality to Day 90 and described as the percentage alive at day 90, counting participants discharged home earlier as alive. The registry record does not report a single primary-outcome comparison or its uncertainty. It lists 16 outcome measures and 1 analysis, but does not report the analysis populations, missing-data methods, multiplicity approach, or the trial’s sample-size justification.