This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Up-Down Determination of the ED90 of Phenylephrine for Hypotension Prophylaxis in Cesarean Delivery (NCT00796328), a na phase 4 study. The primary outcome is Effective Dose of Phenylephrine at Which 90% of Subjects Have no Spinal Induced Hypotension.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00796328 |
| Phase | Phase 4 |
| Condition | Spinal Induced Hypotension in Cesarean Delivery |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | Quadruple |
| Enrollment | 45 |
| Arms in the primary outcome | n/a |
| Lead sponsor | IWK Health Centre |
| Results posted | Yes |
2. Clinical Question
Population
Parturients undergoing elective cesarean delivery with spinal anesthesia are the population described in the study summary. The condition listed in the registry record is spinal-induced hypotension in cesarean delivery. Further eligibility details and a more specific description of the analyzed population are not reported in the registry record.
Intervention
The intervention is a phenylephrine infusion. The study was designed to identify the initial infusion rate associated with the target response. The registry describes the desired response as no spinal-induced hypotension, but does not report the dose sequence used for individual participants.
Comparator
There is no separate comparator group in the registered design. The study is listed as single-group, and allocation is recorded as not applicable. The planned dose-finding question is therefore not a randomized comparison of phenylephrine against another treatment or against no infusion.
Primary question
What initial rate of phenylephrine infusion is associated with no spinal-induced hypotension in 90% of participants undergoing cesarean delivery? This is an ED90 dose-finding question. The investigators hypothesized that the ED90 would be between 40 - 60 mcg/min. That stated hypothesis is a proposed range, not an observed estimate. The registry record does not report the ED90 result or a statistical estimate of its uncertainty.
3. Trial Design
The registry identifies this as a Phase 4, single-group study of phenylephrine infusion for prophylaxis of spinal-induced hypotension during cesarean delivery. The allocation field is recorded as not applicable, consistent with a dose-finding study without a listed randomized control arm. The study is marked quadruple masked, but the registry record does not specify which groups of people were masked or how masking was maintained.
The study planned to use an up-down methodology to estimate the initial infusion rate associated with the desired response. In general, an up-down dose-finding approach uses observed responses to guide which dose is considered next. The registry description says this method is used to identify a dose at which the desired response occurs in over 90% of subjects. However, details of the sequence, dose increments, response-based adjustment rules, and stopping criteria are not reported in the registry record.
The registry lists enrollment of 45 and a status of terminated. The recorded study start is 2008-11, and primary completion is recorded as 2009-02. The record does not explain why the study was terminated, whether enrollment was completed as planned, or how many participants contributed data to the primary endpoint. Those details should not be inferred from the enrollment field alone.
The primary outcome is an ED90 for phenylephrine, with a timeframe from spinal administration until delivery. No randomized treatment comparison is listed, and the registry record contains no analysis entry for the primary outcome. Thus the design and stated objective are available, but the record does not provide an analyzed dose estimate or enough operational detail to reconstruct the dose-finding procedure.
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: Six subjects were withdrawn from the study
Overall Study
| Stage | Phenylephrine Infusion |
|---|---|
| STARTED | 46 |
| COMPLETED | 40 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | Phenylephrine Infusion |
|---|---|
| experienced hypotension requiring tx | 6 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Phenylephrine Infusion |
|---|---|---|
| Participants analysed | 46 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 46 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 46 |
| Sex: Female, Male: Male | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Effective Dose of Phenylephrine at Which 90% of Subjects Have no Spinal Induced Hypotension, measured over Spinal administration until delivery.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | dose of phenylephrine |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the effective dose of phenylephrine at which 90% of subjects have no spinal-induced hypotension. The registry describes this as an ED90, expressed as a dose of phenylephrine, and gives the timeframe as spinal administration until delivery. It is a dose-finding endpoint: rather than asking whether one assigned treatment differs from a control, it aims to identify the infusion rate associated with a specified response probability.
That endpoint is useful for translating a dose-response question into a target dose. The response definition matters because the ED90 depends on what counts as a positive response. In this record, a positive response is described as no drop in blood pressure or no spinal-induced hypotension. The exact measurement rules, threshold for a drop in blood pressure, and handling of events during the timeframe are not reported in the registry record.
The investigators hypothesized an ED90 between 40 - 60 mcg/min. This is the stated hypothesis, not a reported endpoint value. The registry record does not include an ED90 estimate, confidence interval, or other primary endpoint analysis. Therefore, it does not show whether the target response probability was reached at a particular infusion rate or how precisely the ED90 was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes a dose-finding objective, but it does not report a numerical result for that objective. The primary endpoint is the ED90 of phenylephrine for preventing spinal-induced hypotension, defined in the study description as the dose at which 90% of subjects have no such hypotension. Although the investigators hypothesized an ED90 between 40 - 60 mcg/min, that range should not be read as the study's finding. No estimated ED90 is reported in the registry record.
Without a dose estimate and its uncertainty, the precision of the result cannot be assessed. A confidence interval, when reported, describes uncertainty around an estimate under the analysis assumptions; its width helps readers judge how much the estimate could vary. The registry record does not report a confidence interval or another measure of uncertainty for the ED90. It also does not provide response counts by dose, a dose-response curve, or an analysis method that would allow the estimate to be independently examined.
The study is single-group, and allocation is recorded as not applicable. The primary question is therefore not a contrast between phenylephrine and a control treatment. The record does not support a randomized comparative conclusion about relative effects. Nor does the lack of a reported ED90 establish that phenylephrine did or did not prevent hypotension; it means that the registry record does not provide the primary analysis needed to evaluate that dose-finding objective.
The enrollment field lists 45, while the adverse-event summary lists 40 at risk in the phenylephrine infusion group. These fields refer to different registry entries and should not be treated as interchangeable descriptions of the primary endpoint population. The number contributing to the ED90 analysis is not reported in the registry record, and no explanation for the difference in recorded counts is given.
The registry status is terminated, but no reason for termination is stated. Termination alone does not establish whether the study stopped early, whether planned enrollment was reached, or whether the primary analysis was completed. The recorded primary completion date and enrollment field do not fill in those missing details. The result should therefore be read as an incompletely reported dose-finding record: the objective and hypothesis are documented, but the primary estimate and its precision are not.
9. Statistical Methods Explained
The statistical aim is to estimate a dose associated with a target response probability. An ED90 is a dose at which the desired response is expected in 90% of the target population, according to the dose-response model or method used. Here, the desired response is described as no spinal-induced hypotension. The registry record gives the target and the general up-down approach, but does not report the estimation algorithm or a numerical estimate.
What does an up-down method do?
In general, an up-down design uses participant responses at assigned doses to inform dose selection as the study proceeds. Depending on the specific method, the next dose may move upward or downward in response to the preceding outcome. This can concentrate observations around a response transition and support dose estimation. The term covers different procedures, however, and the exact procedure matters for interpreting an estimate. The registry record does not state the dose adjustment rule, starting dose, dose steps, response window beyond spinal administration until delivery, or stopping rule. It is therefore not possible to determine from the record how the sequence was implemented.
Why does the response definition matter?
A dose-finding estimate depends on how the target response is classified. The record describes a positive response as no drop in blood pressure and also describes the endpoint as no spinal-induced hypotension. It does not report a blood-pressure threshold, measurement schedule, or adjudication procedure. Those details can influence whether a participant is classified as having the desired response. The record also does not say how observations with incomplete measurement or uncertain classification were handled.
What would uncertainty around the ED90 tell readers?
A point estimate alone describes a selected dose, while an uncertainty interval indicates how precisely the data locate the dose associated with the target response. In dose-finding, uncertainty can depend on the number and placement of observations across doses, the response pattern, and the estimation method. A confidence interval is one way to communicate that uncertainty. No interval, standard error, model output, or response-by-dose data is reported in the registry record, so precision cannot be evaluated. The hypothesized range of 40 - 60 mcg/min is not a confidence interval and is not a result.
How should the planning illustration be understood?
The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated share of the observed effect. These are assumptions for a comparison-style planning exercise, not a description of the registered single-group up-down design. The record does not give the calculated planning values in the registry record for this analysis. Such sample-size illustrations are planning scenarios; they are not observed power and do not show what the completed study achieved.
For this dose-finding objective, the key information would be the observed dose-response outcomes and the method used to turn those outcomes into an ED90 estimate. The registry record does not report those details or an analysis entry. No recalculated estimate can be produced from the record's endpoint description alone. General methods such as fitting a dose-response model or applying a particular up-down estimator would require data and assumptions not reported.
What role can over-dispersion play?
Generally, over-dispersion means that observed variability is greater than a model assumes. In a dose-response analysis, a model that understates variability can give overly narrow uncertainty estimates. Appropriate modeling and diagnostics depend on the data structure and analysis plan. The registry record does not report a model, dispersion assessment, diagnostics, or uncertainty estimate, so there is no basis for saying whether over-dispersion was present or how it was handled.
The design is recorded as quadruple masked, but the registry does not explain who was masked or how that status applied to dose assignment, outcome assessment, or analysis. Masking can help limit some sources of bias, but the label alone does not describe its practical implementation. Likewise, the registry does not report protocol deviations, analysis exclusions, or a prespecified statistical analysis plan. These omissions limit evaluation of how the stated ED90 objective was analyzed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a single primary outcome measure: the effective dose at which 90% of subjects have no spinal-induced hypotension. It does not report a multiplicity adjustment or a hierarchy for testing multiple primary hypotheses. With one listed primary measure, the record does not establish that no additional analyses were conducted; the full analysis plan and any secondary outcomes are not reported in the registry record.
The registry record does not describe how missing blood-pressure observations or incomplete outcome assessments were handled. It does not say whether participants with incomplete observations were excluded, retained under an imputation approach, or handled by another rule. The number of participants included in the primary endpoint analysis is also not reported. Since the primary outcome depends on classifying responses over a defined timeframe, missingness and classification rules could affect the ED90 estimate.
No analysis population is specified. The record does not identify whether the primary analysis used all enrolled participants, only participants who received the infusion, or another defined group. It also does not report protocol deviations or exclusions from analysis. The enrollment field lists 45, but that alone does not establish the number analyzed for the primary endpoint.
These are reporting gaps, not evidence that the study failed to address multiplicity or missing data. The statistical plan, analysis populations, missing-data procedures, and any sensitivity analyses are not reported in the registry record. As a result, readers cannot assess how those decisions were made or how robust the primary endpoint result would be to alternative assumptions.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Phenylephrine Infusion | 0 | 40 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Phenylephrine Infusion | 0 of 40 |
The registry adverse-event summary lists the Phenylephrine Infusion group with 40 at risk for serious adverse events and 0 affected. It also lists 40 at risk for other adverse events and 0 affected. These are the counts recorded in the safety summary; they should be read as registry-reported counts, not as a complete account of every possible safety outcome.
The death count is not reported in the registry record. The summary does not provide an adverse-event observation period, event definitions, severity criteria, or details about how events were collected. The primary outcome timeframe is spinal administration until delivery, but the registry does not state that this was also the safety-assessment timeframe.
The enrollment field lists 45, whereas the safety summary lists 40 at risk. The record does not explain the difference. These safety counts do not establish the number included in the primary endpoint analysis, and they do not provide a comparison against another group. The absence of affected participants in the recorded categories should be interpreted narrowly: the registry reports 0 in each listed category among the participants counted at risk, with further ascertainment details not reported.
12. What the Result Does, and Does Not, Mean
The record describes a study intended to estimate the phenylephrine infusion rate associated with no spinal-induced hypotension in 90% of participants undergoing cesarean delivery. It identifies the ED90 as the primary outcome and states the investigators' hypothesis that the dose would be between 40 - 60 mcg/min. These details clarify the question the study was designed to address.
They do not establish the answer. The registry record does not report an ED90 estimate, response data by dose, or uncertainty around an estimate. The stated hypothesized range must not be interpreted as a dose shown to meet the target. Without a reported analysis, the record cannot establish how closely the study's data supported the target response probability or how precise any dose estimate would be.
The single-group design also sets limits on what can be inferred. It is a dose-finding study, not a randomized comparison against a control group. The record therefore does not provide a comparative estimate of effect. The safety summary reports zero affected in the listed serious and other adverse-event categories, but its event definitions and assessment period are not reported; those entries do not constitute a complete safety evaluation.
The status is terminated, but the registry does not give the reason. That status should not be taken as proof of a particular outcome, early stopping decision, or analysis problem. The most defensible reading is that the registry documents the objective, design features, and some safety counts, while leaving the primary dose estimate and key analysis details unavailable. Conclusions about the ED90 itself cannot be drawn from the registry record.
13. Why This Trial Matters Statistically
This study illustrates a statistical question that differs from the usual treatment-versus-control comparison. A dose-finding study seeks a dose associated with a specified probability of response. The target is no spinal-induced hypotension in 90% of subjects, making the endpoint an ED90 rather than a contrast between treatment groups. That distinction affects what information readers need: dose assignments, response definitions, the estimation procedure, and uncertainty around the estimated dose.
The up-down method is relevant because it uses response information to guide dose selection. In general, this approach can be useful when the scientific goal is to locate a dose-response region efficiently. But an estimate cannot be judged from the method's name alone. Implementation details and the response pattern are essential to understanding how the result was obtained. Those details, along with the primary ED90 estimate, are not reported in the registry record.
The record also shows why planning calculations need to match the study design and target estimand. The described planning assumptions use equal allocation between two arms and a normal approximation, while the registered study is single-group and seeks a dose threshold. The planning illustration is not evidence of the study's achieved precision or observed power, and it does not replace a reported dose-finding analysis.
Finally, the record distinguishes between a clearly stated scientific objective and a reported statistical result. The objective and hypothesized range are documented; the primary estimate and its uncertainty are not. That gap matters because a target dose is most informative when readers can evaluate both its estimated value and the precision and assumptions behind it.
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 principal limitation of the available record is that it does not report the primary ED90 estimate or its uncertainty. The study's objective and hypothesized range are stated, but there are no reported dose-specific responses, confidence interval, or analysis output with which to evaluate the endpoint.
Implementation details needed to assess the up-down method are also absent. The starting dose, dose increments, dose adjustment rules, stopping criteria, and estimator are not reported in the registry record. The outcome definition is described as no spinal-induced hypotension, but operational details for blood-pressure measurement and response classification are not provided.
The record marks the study as terminated without giving a reason. It lists enrollment of 45, while the safety summary lists 40 at risk; the record does not explain the difference or state how many participants contributed to the primary analysis. The analysis population, missing-data procedures, exclusions, protocol deviations, and sensitivity analyses are not reported.
The quadruple-masking label is not accompanied by details identifying who was masked or how masking was implemented. The registry also does not report an analysis plan or the safety observation period and event definitions. These limitations restrict interpretation of both the dose-finding objective and the safety counts. They are gaps in the registry record and should not be filled by assumptions about how the study was conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Up-Down Determination of the ED90 of Phenylephrine for Hypotension Prophylaxis in Cesarean Delivery — NCT00796328.
- Registry record last updated 2018-04-23; status last verified 2018-03.
- Results first posted 2014-04-21.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00796328 is a Phase 4, single-group study of phenylephrine infusion for prophylaxis of spinal-induced hypotension in parturients undergoing cesarean delivery. The study used an up-down dose-finding objective to estimate the ED90, defined as the dose associated with no spinal-induced hypotension in 90% of subjects. The investigators hypothesized an ED90 between 40 - 60 mcg/min.
The registry lists enrollment of 45, quadruple masking, and terminated status. The recorded start is 2008-11, and primary completion is recorded as 2009-02. The primary endpoint timeframe is spinal administration until delivery. The registry record does not report an ED90 estimate, endpoint analysis, or reason for termination.
The safety summary lists 0 serious adverse events and 0 other adverse events among 40 at risk in the phenylephrine infusion group. A death count and further safety-assessment details are not reported in the registry record.