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 Treatment Study of Bipolar Depression (NCT00947791), a randomized phase 4 study. The primary outcome is Montgomery-Asberg Depression Rating Scale (MADRS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00947791 |
| Phase | Phase 4 |
| Condition | Bipolar Disorder |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Icahn School of Medicine at Mount Sinai |
| Results posted | Yes |
2. Clinical Question
Population
People with bipolar depression described as treatment-resistant. The registry lists Bipolar Disorder as the condition. It reports an enrollment of 1, but the primary outcome states that 0 participants were analyzed because of confidentiality concerns.
Intervention
A single intravenous ketamine infusion on a treatment day. The record describes the study purpose as evaluating a single intravenous administration of an N-methyl-D-aspartate antagonist for acute treatment.
Comparator
A single intravenous midazolam infusion on a treatment day. Participants were assigned to ketamine followed by midazolam, or midazolam followed by ketamine, with the treatment conditions 2 weeks apart.
Primary question
How does the Montgomery-Asberg Depression Rating Scale (MADRS) score 24 hrs post-infusion compare with baseline in this crossover study? The record gives no analyzed MADRS result, so it does not report the size or precision of a treatment comparison.
The study’s stated purpose was to determine whether a single intravenous administration of an N-methyl-D-aspartate antagonist is safe and effective for acute treatment of bipolar depression. The registry identifies ketamine and midazolam as the two drug conditions and describes both treatment sequences. The primary outcome is named as MADRS, with the assessment time framed as 24 hrs post-infusion compared to baseline.
The clinical question is therefore clear at the level of intended comparison, but the posted results do not answer it. The primary outcome says that 0 participants were analyzed for confidentiality concerns, and the record lists 0 analyses. There is no reported effect estimate, uncertainty interval, or test of the treatment contrast. The enrollment figure alone cannot substitute for analyzed outcome data.
3. Trial Design
The registry describes a Phase 4 randomized, double-masked crossover study. It lists an enrollment of 1 and identifies two possible treatment sequences: ketamine followed by midazolam, and midazolam followed by ketamine. Participants in either sequence were to receive both conditions, each as a single intravenous infusion on a treatment day. The two treatment conditions were scheduled 2 weeks apart.
In a crossover design, each participant may contribute observations under both conditions. This makes within-participant comparisons possible when outcomes are collected and analyzed. Randomizing treatment order can help prevent sequence assignment from being determined by participant or investigator preference. Double masking is intended to limit knowledge of the assigned condition; the registry does not describe who was masked or how masking was maintained.
The study started in 2009-07, had a primary completion date of 2009-10, and is listed as terminated. The reason for termination is not reported in the registry record. The record does not describe a washout rationale, the handling of period or carryover effects, or the detailed visit schedule beyond the infusion timing and the primary outcome timeframe.
There is an important distinction between the registry’s enrollment figure and the primary outcome population. The record reports enrollment of 1, while also stating that 0 participants were analyzed for the primary outcome because of confidentiality concerns. It does not establish what data were collected or whether any participant completed both treatment conditions. No analyzed treatment comparison can be inferred from the design description.
The sponsor is Icahn School of Medicine at Mount Sinai. The registry lists five secondary outcomes: QIDS-SR, YMRS, BPRS, CADSS, and SAFTEE. It reports 6 outcome measures overall, but the additional measure is not identified in the record as presented. The outcomes’ analysis methods and results 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.
Overall Study
| Stage | Ketamine/Midazolam | Midazolam/Ketamine |
|---|---|---|
| STARTED | 0 | 1 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Based on confidentiality concerns, 0 participants analyzed.
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: Based on confidentiality concerns, 0 participants analyzed.
| Characteristic | Unit | Ketamine/Midazolam | Midazolam/Ketamine | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | |
| Sex: Female, Male: Female | — | — | 0 | |
| Sex: Female, Male: Male | — | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Montgomery-Asberg Depression Rating Scale (MADRS), measured over 24 hrs post-infusion compared to baseline.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the Montgomery-Asberg Depression Rating Scale (MADRS), with the timeframe described as 24 hrs post-infusion compared to baseline. This frames the outcome as a change-related assessment around an infusion, relevant to the study’s stated focus on acute treatment of bipolar depression. A defined clinical measure can give investigators a consistent way to assess a clinical construct, rather than relying only on a general impression. The registry does not provide the MADRS unit, parameter, or dispersion, however, so the precise form of the endpoint cannot be determined from the record.
The registry does not report a numerical baseline value, a post-infusion value, a change estimate, or a contrast between ketamine and midazolam. It states that 0 participants were analyzed for this outcome because of confidentiality concerns. Consequently, the endpoint’s intended timing is reported, but no outcome magnitude or precision is available. No direction of change or comparative result can be established from the posted record.
The distinction between the endpoint definition and an endpoint result matters. Naming MADRS and specifying a timeframe describes what the study intended to assess. It does not provide the data needed to judge the observed response or how uncertain an estimate would be. The clinical interpretation therefore remains unresolved in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and design, but it does not provide analyzable primary outcome results. The primary outcome entry states that 0 participants were analyzed, citing confidentiality concerns. The record also lists 0 analyses. There is no reported MADRS estimate, treatment contrast, confidence interval, or hypothesis test from which to characterize the direction, size, or precision of a difference.
The enrollment figure is 1, but enrollment and analysis are different stages. The enrollment count does not show that usable outcome data were available, that both crossover periods were completed, or that a treatment comparison could be calculated. The reason given for having no primary outcome participants analyzed is confidentiality; the record does not give further details about data collection or participant completion.
The safety entries also require careful interpretation. For each sequence, the registry reports 0 participants at risk and 0 serious and other adverse events, along with 0 deaths. Because the at-risk counts are 0, these entries do not establish that participants experienced no adverse events. They indicate that the record contains no safety population from which event occurrence or frequency can be assessed. The listed zeros should not be treated as evidence of safety.
The study is marked terminated, but the reason for termination is not reported in the registry record. The dates recorded are 2009-07 for study start and 2009-10 for primary completion. Those dates do not explain why the study ended, nor do they indicate whether the planned outcome assessments were completed. The registry’s status and dates should therefore be kept separate from conclusions about the study’s execution or findings.
The crossover format could support a within-participant comparison if observations under both treatments were available and analyzed. Here, no such comparison is reported. There are also no reported estimates for the secondary measures, which include QIDS-SR, YMRS, BPRS, CADSS, and SAFTEE. Although 6 outcome measures are listed overall, the record does not provide results for them.
A planning illustration based on an observed effect is not a substitute for trial evidence or an observed-power calculation. The planning assumptions state a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Those calculations are planning illustrations, not observed power. With no analyzed primary outcome result reported, they cannot resolve the clinical comparison. The posted data support no conclusion about whether one treatment condition produced a larger or smaller MADRS change.
9. Statistical Methods Explained
The record identifies randomization, double masking, and a crossover model. These labels describe aspects of the intended design, not the results of a statistical analysis. The registry does not report an analysis method, and it lists 0 analyses. The methods below explain the general statistical ideas relevant to this design; they do not describe analyses shown to have been carried out in this study.
What does randomization contribute?
Randomization assigns treatment order by a chance-based process rather than by participant or investigator choice. In general, this can reduce systematic differences between assignment groups. In a crossover study, the randomized assignment concerns sequence: the record lists ketamine followed by midazolam and midazolam followed by ketamine. Randomization does not ensure that every possible source of bias is removed, and it cannot replace outcome data. The record does not describe the randomization procedure, allocation concealment, or whether the planned sequence assignments were completed.
How does a crossover comparison work?
In general, a crossover design exposes a participant to each treatment condition at different times. When outcome measurements are available for both conditions, the analysis can compare each participant with themself. This can account for stable differences between participants and may make a within-participant contrast informative. The registry describes a single infusion for each condition, with the conditions 2 weeks apart, but does not report whether both periods were completed or provide any paired outcomes.
Repeated treatment periods also make timing relevant. Outcomes may be affected by period effects, changes over time, or residual effects from an earlier treatment. A washout interval or other design feature may be used to address such concerns in some studies, but the registry record does not report a washout rationale or how period and carryover effects would be assessed. It also does not specify whether the planned analysis would account for treatment order or period.
What does double masking mean statistically?
Masking is intended to limit the influence of knowledge about treatment assignment on treatment delivery, participant reports, or outcome assessment. In general, reducing such knowledge can help guard against some forms of bias. The registry labels this study double-masked but does not identify which roles were masked, how the two infusions were made indistinguishable, or whether masking was evaluated. The label alone cannot establish that masking was successful.
What information would an effect estimate convey?
An effect estimate would summarize the observed contrast between conditions for a defined endpoint. A confidence interval, in general, describes the uncertainty associated with an estimate under the assumptions of the analysis. It helps distinguish a precise estimate from one compatible with a broad range of values. Neither an estimate nor a confidence interval for MADRS is reported, so the magnitude and precision of the intended treatment comparison are unavailable. The registry also does not report a p-value or a statistical test for this outcome.
Why do outcome definitions matter?
The primary outcome is MADRS at 24 hrs post-infusion compared to baseline. That wording supplies a measure and assessment timeframe, but the unit, parameter, and dispersion are not stated. The record does not clarify whether the intended statistic was a within-condition change, a comparison of changes between conditions, or another summary. A statistical contrast must be defined before its estimate can be interpreted; without that detail and analyzed data, no treatment effect can be reconstructed.
What can the planning assumptions tell readers?
The registry describes sample-size calculations as planning illustrations based on an observed effect, not as the study’s own design justification. The stated assumptions include a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. In general, planning calculations estimate how much information a future study might need under specified assumptions. They are not evidence that an effect was observed, and they are not observed power. The specific design justification is not reported in the registry record. With no analyzed primary outcome estimate available, the planning illustration should not be read as an empirical treatment result.
More broadly, statistical interpretation depends on the outcome data, the contrast being estimated, and the assumptions used in the analysis. The record gives design labels and outcome names, but it does not report an analysis plan, estimation method, uncertainty measure, or result. Accordingly, the general concepts above explain what the methods could mean, not what an unreported analysis found.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 6 outcome measures overall and names five secondary outcomes: QIDS-SR, YMRS, BPRS, CADSS, and SAFTEE. MADRS is identified as the primary outcome. The record does not report whether there were additional outcome measures beyond those named, or how the outcomes were organized for analysis.
When several outcomes are tested, multiplicity can increase the chance of finding at least one apparently notable result by chance. Statistical approaches can account for multiple comparisons, or a study can define a limited set of primary hypotheses in advance. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or the number of planned tests. No result is available to assess under any such strategy.
The primary outcome entry says that 0 participants were analyzed because of confidentiality concerns. This is an analysis-population statement, not a description of how missing values were handled. The record does not report whether outcome data were collected, why they were unavailable for analysis beyond the stated confidentiality concern, or whether any imputation or other missing-data method was used. The enrollment figure of 1 does not establish the availability of analyzable observations.
The planned crossover design would ordinarily require attention to whether measurements from both conditions are available for a participant. The record does not report completion by treatment period or define an analysis population such as all randomized participants or participants who completed both periods. With 0 analyses listed and no outcome estimates reported, neither multiplicity nor missing-data handling can be evaluated empirically.
11. What the Result Does, and Does Not, Mean
The record documents a randomized, double-masked crossover study of ketamine and midazolam for treatment-resistant bipolar depression. It identifies MADRS at 24 hrs post-infusion compared to baseline as the primary outcome and describes two treatment sequences with the conditions 2 weeks apart. These details show what the study set out to assess, not what the comparison found.
The posted results do not show an analyzed primary outcome. The registry states that 0 participants were analyzed because of confidentiality concerns and lists 0 analyses. No numerical change, treatment contrast, uncertainty interval, or significance test is reported. As a result, the record cannot establish the direction or size of a difference between ketamine and midazolam, or how precisely such a difference might have been estimated.
The adverse-event entries likewise do not establish that there were no harms. Each sequence has 0 participants at risk and zero counts for the listed event categories and deaths. With no participants represented in the at-risk counts, the record does not provide a basis for estimating adverse-event occurrence. The entries should not be interpreted as evidence that either condition caused no adverse events.
The record does not report why the study was terminated, whether both periods were completed, or why the outcome data were not analyzed beyond the stated confidentiality concern. It also does not report results for the listed secondary outcomes. The registry information is therefore descriptive of the intended design and the absence of analyzable posted results; it does not resolve the clinical question of comparative effect or safety.
12. Why This Trial Matters Statistically
This study is statistically notable because its design and outcome are identifiable, while its posted analysis is not. The randomized crossover structure indicates an intended comparison of two treatment conditions within treatment sequences. The primary endpoint and assessment timeframe are also named. Yet the registry reports 0 participants analyzed for the primary outcome and 0 analyses, leaving no estimate to interpret.
This distinction matters when reading a trial record. Design features describe how a study was planned or organized; outcome results describe what the collected data show. Randomization and masking do not themselves establish a treatment effect, and enrollment does not guarantee an analyzable outcome. Here, the enrollment figure is 1, while the primary outcome explicitly reports 0 participants analyzed because of confidentiality concerns.
The safety entries illustrate another interpretive issue. Event counts of zero can appear reassuring when read in isolation, but the accompanying at-risk counts are also zero. Without a reported safety population, these entries cannot support conclusions about adverse-event rates. This is a useful reminder that counts need their denominators and analysis context to be meaningful.
The record also names multiple outcome measures without reporting results or a multiplicity approach. Those omissions limit assessment of how outcomes were prioritized and how uncertainty across comparisons would have been handled. The statistical importance of the record is thus less about an estimated treatment difference and more about the boundary between a documented study design and unavailable outcome evidence.
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 limitation is the absence of analyzable outcome results. The registry reports 0 participants analyzed for MADRS because of confidentiality concerns and lists 0 analyses. It gives no numerical endpoint values, treatment contrast, confidence interval, p-value, or secondary outcome estimates. The clinical comparison cannot be assessed from the posted record.
The enrollment entry is 1, but it does not clarify whether the participant received both infusions, completed both periods, or contributed data to any outcome. The reason stated for the lack of primary outcome analysis is confidentiality; further details about data availability are not reported in the registry record. The analysis population and handling of missing data are also not reported.
The status is terminated, but the reason for termination is not reported in the registry record. The record does not explain whether termination affected enrollment, follow-up, or analysis. The start and primary completion dates are 2009-07 and 2009-10, but those dates do not resolve those questions.
Although the registry labels the study randomized and double-masked, it does not describe the randomization method, masking procedures, or any assessment of masking. It also does not report the analysis plan, treatment-period handling, consideration of carryover, multiplicity strategy, or sample-size justification. The listed planning illustration is not a substitute for those details or for observed outcome estimates.
Finally, safety entries report 0 participants at risk for both treatment sequences. Their zero event counts therefore cannot be used to characterize the frequency of harm. These limitations are specific to the information available in this registry record and should not be mistaken for evidence about unreported results.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Treatment Study of Bipolar Depression — NCT00947791.
- Registry record last updated 2017-05-17; status last verified 2017-04.
- Results first posted 2017-05-17.
- 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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17. Record Summary
The registry describes NCT00947791, titled Treatment Study of Bipolar Depression, as a Phase 4 randomized, double-masked crossover study of intravenous ketamine and midazolam in bipolar depression. Its stated purpose was to assess a single intravenous administration of an N-methyl-D-aspartate antagonist for acute treatment. Participants were assigned to one of two treatment sequences, with each condition given as a single infusion and the conditions 2 weeks apart.
MADRS at 24 hrs post-infusion compared to baseline is the primary outcome. The record reports enrollment of 1, but states that 0 participants were analyzed for the primary outcome because of confidentiality concerns. It lists 0 analyses and provides no analyzed treatment comparison. The study is marked terminated; the reason is not reported in the registry record.
The record names QIDS-SR, YMRS, BPRS, CADSS, and SAFTEE as secondary outcomes. Safety entries list 0 participants at risk in each sequence, so the event counts do not establish safety outcomes. The sponsor is Icahn School of Medicine at Mount Sinai.