Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis (NCT01694069), a randomized phase 4 study. The primary outcome is Change in Forced Expiratory Volume at One Second (FEV1).

2. Clinical Question

3. Trial Design

The registry describes a Phase 4, randomized, quadruple-masked, parallel-group study of piperacillin-tazobactam in people with cystic fibrosis and pulmonary exacerbations. The listed sponsor is West Virginia University. The study start is recorded as 2012-09, and primary completion is recorded as 2013-09. Its status is terminated. The registry record does not report the reason for termination or a termination date.

The parallel design means the planned comparison assigned participants to one of two regimens: continuous infusion or intermittent infusion. The continuous regimen was 400 mg/kg/day, up to 16 grams, administered continuously over 24 hours, once daily. The intermittent regimen was the same stated daily dose and maximum, divided into four equal doses administered over 30 minutes, four times a day. These are the regimens described in the arm records; details about adherence or any treatment changes are not reported.

Randomization is the registry's design classification. In general, random assignment is used to reduce systematic differences between groups at the start of a study. The record does not describe how the random sequence was generated, how assignments were concealed, or how randomization was implemented. Quadruple masking is also the registry's classification, but the record does not identify which people or roles were masked or explain how masking was maintained.

The registry lists an enrollment of 6. This entry does not establish how many participants were randomized, received each regimen, completed follow-up, or were included in analyses. Those counts are not reported in the registry record. Although the record lists the study as randomized and parallel, no protocol-level statistical plan, allocation details, or analysis population definitions are reported. The status is terminated, and the registry states that the original principal investigator left the institution. The reason for termination is not reported.

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

Analysis population for the primary outcome, as defined in the registry: The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

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.

Population: The study was terminated and the original PI has left the institution. Minimal results information is available; all efforts were made to retrieve more results information, but were unsuccessful. The available data does not indicate in which arm the participants were enrolled, therefore all available study data with be entered under All Study Participants.

6. Primary Endpoint

The registry lists the primary outcome as Change in Forced Expiratory Volume at One Second (FEV1), measured over Baseline, Day 0, and Day 14.

The primary endpoint was change in forced expiratory volume at one second (FEV1). FEV1 is the amount of air a person can forcefully exhale during the first second of an effort; in general, it is used as a measure of lung function. It provides a numeric outcome that can be assessed at different visits, making it possible to describe change over the treatment period.

The registry specified measurements at enrollment (Day 0) and at the end of therapy (Day 14). If a stable FEV1 measurement from before enrollment was available, that value was to serve as baseline. Change was to be calculated from baseline, when available, to Day 14, and also from Day 0 to Day 14. Those are two potential reference points for describing change; the record does not report which baseline definition was used in an analysis or how results from the two calculations were to be handled together.

Comparing change between the infusion groups would address whether the groups' measured lung-function trajectories differed during the specified treatment period. In general, a change endpoint can account for the starting measurement, but its interpretation depends on the baseline definition, availability of follow-up measurements, and analysis method. Those details and the FEV1 results are not reported in the registry record. The endpoint is therefore a planned measure, not evidence of an observed difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on both the design and the outcome data. The registry describes randomization, masking, two parallel treatment arms, and a planned change in FEV1. It does not report an analysis plan or results. The general concepts below explain what such methods can address; they should not be read as a description of analyses actually performed in this study.

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance. Its purpose is to reduce the likelihood that systematic differences in participant characteristics determine which regimen is received. It does not guarantee that groups will be identical, particularly in a small study, and it does not remedy missing outcome data or incomplete reporting. Here, the record identifies the study as randomized, but the sequence-generation and allocation procedures are not reported. It is therefore not possible to assess implementation from the registry record.

How would a change comparison be interpreted?

In general, a change score describes the difference between a measurement at follow-up and a reference measurement at baseline. A between-group comparison of change asks whether the measured changes differed between the assigned regimens. The registry describes two possible calculations: baseline, if a stable pre-enrollment value was available, to Day 14; and Day 0 to Day 14. The exact analysis used, the handling of participants without a stable pre-enrollment measurement, and whether the two change definitions were separate analyses or alternatives are not reported.

A change estimate is most informative alongside an uncertainty interval. In general, a confidence interval gives a range of values compatible with the data and the model's assumptions, and communicates the precision of an estimate. A narrow interval indicates greater precision than a wide interval; an interval that includes no difference does not by itself prove that groups are equivalent. Since this record reports no estimate or interval, neither the direction nor the precision of the primary comparison can be described.

What can a significance test tell readers?

In general, a statistical test evaluates how compatible the observed data are with a specified null hypothesis under assumptions. A p-value is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. Interpretation normally considers the estimated effect, its uncertainty, the endpoint definition, and the analysis plan together. No p-value or test result is reported for the primary endpoint. The registry record also does not state a planned significance threshold or whether testing would be one-sided or two-sided.

What is the role of planning calculations?

The registry's stated assumptions for planning illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such calculations, in general, illustrate the number of participants per arm needed under specified assumptions. They are not observed power and do not demonstrate that a study had a particular chance of detecting an effect after results are known. The outcome effect needed to anchor these illustrations is not reported in this record, and no analysis results are available to support an interpretation of an observed-effect-based calculation.

For time-to-event outcomes, the record describes planning illustrations in terms of the total number of events, using the Schoenfeld method; other illustrations are described in participants per arm. This distinction matters generally because time-to-event precision depends on event information, while other designs may be expressed in participant counts. The registry lists time-to-next pulmonary exacerbation as a secondary outcome, but does not report event counts, estimates, or a time-to-event analysis. No planning values are reported in the registry record from which a study-specific calculation can be discussed.

Why do masking and the analysis plan matter?

In general, masking can reduce the influence of expectations on care, outcome assessment, or reporting, depending on who is masked and how. The registry classifies the study as quadruple-masked but does not specify the masked parties or procedures. The statistical plan is also not reported: there is no stated primary contrast, model, covariate adjustment, missing-data method, or analysis population. These omissions prevent a detailed assessment of whether the planned comparison, if conducted, followed a prespecified approach.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures: change in FEV1 as the primary outcome and several secondary outcomes, including serum concentrations, time to the next pulmonary exacerbation, change in questionnaire score, sputum density and weight, time to defervescence, time to white blood cell count normalization, and clinical failure of treatment. When multiple outcomes or multiple analyses are considered, general statistical practice distinguishes a prespecified primary question from secondary or exploratory questions. Testing many outcomes can increase the chance of at least one apparently notable result by chance. The record does not report a multiplicity strategy, hierarchy among secondary outcomes, or which outcomes were formally tested.

The primary endpoint description includes two possible change calculations: stable pre-enrollment baseline to Day 14 when available, and Day 0 to Day 14. How these were handled in the analysis is not reported. The record also does not describe the analysis population, exclusions, or whether analysis followed the assigned treatment groups. These matters are important for understanding what a treatment estimate would represent.

The registry states that the study was terminated and that the original principal investigator left the institution. It also states that efforts to retrieve results information were unsuccessful. FEV1 results and results for the other outcomes are not reported in the registry record. The reasons for missing measurements, the amount of missing data, and any approach to handling missing values are not reported. Without these details, it is not possible to determine whether missingness could have affected an estimate or whether an analysis addressed it.

The record does not report interim analyses, stopping rules, or a statistical plan, and none should be inferred from the terminated status. Termination alone does not indicate why the study stopped or what results may have been available to investigators.

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

The registry record is evidence that a randomized, parallel-group comparison of two piperacillin-tazobactam infusion schedules was registered, and that change in FEV1 was identified as the primary outcome. It also documents the intended measurement times, the regimens, and a terminated status. Those details describe the research question and design; they are not a report of the clinical outcomes observed.

No FEV1 results, treatment-effect estimate, confidence interval, or p-value are reported. Therefore, the registry cannot show whether the measured changes differed between the continuous and intermittent infusion groups, how large any difference was, or whether an estimate was precise. The absence of a reported result is not evidence that the groups had the same outcome, and it is not evidence that one regimen was better. It also cannot establish equivalence or rule out a meaningful difference.

The same distinction applies to the secondary outcomes. Their presence in the registry is not evidence that results were collected, analyzed, or favorable in either direction. The adverse-event entries, with zero participants listed at risk and affected and null death fields, do not establish that there were no harms. The record does not report usable treatment-group safety denominators or outcome results.

The enrollment entry of 6 does not reveal the number randomized, treated, followed, or analyzed. Nor does the terminated status identify the reason for stopping. These limits mean that readers cannot judge the size, completeness, or precision of the study's outcome evidence from the registry record. The most defensible conclusion is about reporting: the planned comparison is documented, but its results are not reported in the registry record. No treatment conclusion follows from that information alone.

12. Why This Trial Matters Statistically

This study illustrates an important distinction between a registered research question and an interpretable statistical result. A clear description of a comparison and endpoint does not itself provide evidence about the size or uncertainty of a treatment difference. For this trial, the record identifies the two infusion strategies and specifies FEV1 change as the primary endpoint, but reports no outcome analyses. Consequently, the central statistical quantities needed to interpret the comparison are unavailable.

The enrollment entry is 6, while the record does not give group-specific numbers or an analysis population. In general, limited enrollment can make estimates less precise and group balance less predictable, but the registry does not provide enough information to quantify precision or assess balance in this study. The issue is not possible to resolve by relying on the design label alone: randomization is a method, not a substitute for complete results.

The record also demonstrates why outcome definitions and measurement availability matter. FEV1 change could use a stable pre-enrollment baseline when available or use Day 0 as the reference. Without an account of which measurements were obtained and how the baseline alternatives were handled, even a reported change would need careful interpretation. Here, neither the measurements nor the analysis are reported.

Finally, the listing of outcomes and adverse-event fields cannot stand in for results. Statistical conclusions require observed data, an analysis that matches the question, and enough information to assess uncertainty and missingness. The registry record does not supply those elements. Its value is in documenting what was intended, while its limitations make clear that no efficacy or safety inference can be drawn from the posted results.

13. 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 trial-specific limitation is the absence of outcome results. The registry states that the study was terminated and that the original principal investigator left the institution; it also says efforts to retrieve results information were unsuccessful. The reason for termination is not reported, and the record does not give a termination date. These details do not establish why results are unavailable or whether results were analyzed elsewhere.

The enrollment entry is 6, but group-specific counts are not reported. The number randomized, treatment received, follow-up completed, and participants included in any analysis are also not reported. It is therefore not possible to assess losses after enrollment, adherence to either infusion regimen, or whether available outcome data came from all enrolled participants.

The registry identifies FEV1 change as the primary endpoint and gives two reference points for calculating change, but the analysis used is not reported. The record does not provide FEV1 values, a treatment contrast, uncertainty estimates, or a statistical test. It also does not describe a statistical analysis plan, missing-data procedures, analysis populations, or any adjustment for multiple outcomes. The masked roles and procedures are not described beyond the quadruple-masked classification.

The adverse-event entries list zero at risk and affected in the two groups, while death counts are null. Because usable denominators and outcome results are absent, these entries cannot support a safety comparison or a conclusion that no adverse events occurred. The record also does not report results for its secondary outcomes. These limitations prevent assessment of both efficacy and safety from the registry record.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis — NCT01694069.
• Registry record last updated 2022-02-01; status last verified 2022-01.
• Results first posted 2022-02-01.
• 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.

17. Record Summary

NCT01694069 is a Phase 4 randomized, quadruple-masked, parallel-group study sponsored by West Virginia University. It compared continuous and intermittent piperacillin-tazobactam for pulmonary exacerbations in people with cystic fibrosis. The registry lists an enrollment of 6 and a terminated status. The study start is recorded as 2012-09, with primary completion recorded as 2013-09.

The primary outcome was change in FEV1, measured at enrollment (Day 0) and Day 14, with a stable pre-enrollment value used as baseline if available. The registry lists nine outcome measures, but reports no outcome results and no analyses. It states that the original principal investigator left the institution and that efforts to retrieve results information were unsuccessful. The reason for termination is not reported. The posted record documents the planned comparison but does not permit an efficacy or safety conclusion.