Telmisartan Pilot Study on Treatment Resistant Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Telmisartan Pilot Study on Treatment Resistant Schizophrenia (NCT03868839), a na phase 2 study. The primary outcome is Changes in Blood Levels of Tumor Necrosis Factor Alpha.

2. Clinical Question

The study’s stated hypothesis focused on whether four weeks of telmisartan at the target dose would alter blood biomarkers related to inflammation and oxidative stress. The listed primary endpoint concerns tumor necrosis factor alpha, an inflammatory biomarker. The record does not establish whether a change was observed or how large or precise any change was. With no comparator, the primary question is a within-group change over time, not a contrast between telmisartan and another treatment or no treatment. The registry record lists six participants enrolled. It does not report how many contributed data to the primary endpoint.

3. Trial Design

This was a phase 2, open-label feasibility trial with a single-group design. The registry record lists six participants enrolled and identifies telmisartan as the intervention. Allocation is recorded as not applicable, and masking as none. There was no randomized control group, so the study cannot directly estimate a difference between telmisartan and a concurrent comparator.

The planned treatment period was 4 weeks. Participants were to take telmisartan 40mg once a day during week 1, with an increase to 80mg, or to the dose tolerated, during the remaining three weeks. The registry’s summary describes the intended population as people with schizophrenia or schizoaffective disorder who had not experienced significant relief of symptoms from current antipsychotic medication. The trial title also refers to treatment-resistant schizophrenia.

The primary completion date is 2020-10-07, and the study status is terminated. The registry record does not report why the study was terminated, whether all planned activities were completed, or how many participants completed treatment and follow-up. It lists four outcome measures, but reports zero analysis entries. The primary endpoint is a continuous measure: blood tumor necrosis factor alpha levels, in pg/mL, at week 4 minus the baseline level.

Open-label means the treatment was not masked from participants or study personnel, as recorded for this trial. In a single-group design, changes over time may be described, but the design does not separate a treatment-related change from other explanations, such as natural fluctuation, concurrent care, or measurement variation. Those considerations are especially important when interpreting a small feasibility study. The registry record does not report a protocol, a sample-size justification, or additional details of the operational design.

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

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: Study is terminated due to lack of funding.

6. Primary Endpoint

The registry lists the primary outcome as Changes in Blood Levels of Tumor Necrosis Factor Alpha, measured over Baseline (week 0) to 4 weeks after initial dose.

The primary endpoint is the change in blood levels of tumor necrosis factor alpha from baseline (week 0) to 4 weeks after the initial dose. It is measured in pg/mL and defined as the week 4 level minus the baseline level. A continuous endpoint retains information about the amount and direction of change, rather than reducing observations to categories such as improved or not improved.

Tumor necrosis factor alpha is identified in the study’s biomarker hypothesis as an inflammation-related measure. Biomarkers can be used to examine biological changes over a study period; they are not, by themselves, a direct measure of symptoms or functioning. The registry record does not report how this biomarker was measured, the assay procedures, or the clinical interpretation intended for a particular amount of change.

The record identifies the endpoint and its timeframe but does not report a mean change, standard deviation, confidence interval, or analysis result. Therefore, the direction, magnitude, and precision of the observed change cannot be described from the registry record. Nor can the endpoint definition alone establish whether any change would be clinically meaningful. The endpoint is a within-group measurement, not a treatment-versus-control contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the endpoint as continuous and specifies the mean as the summary parameter, with standard deviation as the dispersion measure. It defines the outcome as week 4 levels minus baseline levels. The record does not include the numerical mean change or standard deviation, however, and it lists zero analysis entries. The general statistical concepts below explain how such quantities are usually interpreted; they do not describe an analysis result reported for this trial.

What does a mean change describe?

For a continuous endpoint, a mean change summarizes the average difference between each participant’s follow-up measurement and baseline measurement, according to the stated direction of subtraction. Here, the endpoint is explicitly week 4 minus baseline. A negative change would indicate a lower average week 4 level than baseline, while a positive change would indicate a higher average week 4 level. This is a general interpretation of the subtraction rule, not a statement about the trial’s observed direction: the registry record does not report the mean change.

A group mean can be useful for describing the overall pattern, but it does not show how all individual observations behaved. Some participants could have changes in a different direction from the group average. The standard deviation describes the spread of observations around the mean; it is not the same as the uncertainty in the estimated mean. Both the mean and its variability are important for understanding a continuous outcome. Neither numerical summary is reported in the registry record.

What would a confidence interval add?

In general, a confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. It helps readers assess how precisely the data locate the underlying quantity of interest. A narrow interval indicates more precision than a wide interval, although precision does not by itself establish clinical importance or remove design limitations. No confidence interval for this endpoint is reported in the registry record.

A confidence interval would need to be interpreted in relation to the estimand and study design. In this trial, the defined primary quantity is a within-group change over time. Even a precise estimate of that change would not be a randomized comparison of telmisartan with a control treatment. The open-label, single-group design means that statistical precision and causal interpretation are separate issues.

Why does the single-group design matter?

In general, a concurrent comparator can help distinguish changes associated with an intervention from changes that might occur over the same period for other reasons. This trial has no control group and no randomized comparison. As a result, a before-and-after pattern would be descriptive of the enrolled group, but would not isolate the effect attributable to telmisartan. Open-label conduct also means treatment masking was not used, according to the registry record. This can matter when outcomes involve judgment or behavior; the primary outcome is a blood measurement, but the record does not describe assay procedures or any masking of laboratory personnel.

Because the registry lists only six participants enrolled, estimates from the study would also be based on a small group. General statistical reasoning indicates that estimates from small groups can be imprecise and sensitive to individual observations. The actual precision cannot be determined without the observed endpoint values and variability. Enrollment does not confirm that all six participants posted a week 4 measurement.

How should planning calculations be read?

The stated sample-size assumptions describe planning illustrations based on the observed effect, not a sample-size calculation reported as part of the trial’s design. They use a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. These are assumptions for planning, not findings from the trial.

The hypothetical equal-allocation comparison does not match this registry’s single-group design. The record does not state that the trial was planned as a two-arm study, and it does not report a trial-specific sample-size justification. Because the observed effect is not reported in the registry record, the basis for any effect-scaled planning illustration cannot be evaluated from the record. Such calculations should not be read as observed power, evidence of success, or a substitute for an interval around the trial’s actual endpoint estimate.

What can be concluded from the available statistical record?

The endpoint definition and summary-statistic plan are identifiable: a mean change in pg/mL, with standard deviation as the dispersion measure, over the stated baseline-to-week-4 interval. The numerical outcome, uncertainty estimate, and analysis population are not reported in the registry record. The record also lists four outcome measures but zero analysis entries. Accordingly, a quantitative interpretation of the primary endpoint is not possible from this record. General statistical principles can explain what the planned summaries would mean, but they cannot supply the missing trial estimates.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Telmisartan Pill")
n   <- c(5)
m   <- c(1.1)
sp  <- c(0.2377)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Telmisartan Pill  5  1.100  0.238  0.805  1.395

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and identifies changes in blood tumor necrosis factor alpha as the primary endpoint. It does not report the other outcome-measure details in the registry record for this description, nor does it explain whether or how multiple outcomes were handled statistically. A multiplicity strategy, such as prioritizing an endpoint or adjusting interpretation across several tests, is not reported in the registry record. With zero analysis entries and no reported endpoint estimates, the statistical consequences of any multiple testing cannot be assessed.

The registry record also does not report how missing outcome data were handled. It gives an enrollment of six but does not specify how many participants had baseline and week 4 measurements, whether any participants discontinued, or whether any values were excluded. The reason for the terminated status is not reported in the registry record. These missing details matter because the available-data group may differ from the enrolled group, and because the amount and pattern of missingness can affect interpretation.

Analysis populations are not described in the registry record. It is therefore not possible to determine whether the endpoint was intended to be analyzed in all enrolled participants, only participants who completed treatment, or another defined group. The record does not report an intention-to-treat population, a per-protocol population, or rules for handling participants who did not follow the planned dose schedule. These are reporting gaps, not evidence that a particular method was or was not used outside the registry record.

12. 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 non-serious adverse event terms

The registry record reports zero serious adverse events among six participants at risk in the telmisartan group. It also reports zero deaths. For other adverse events, six participants were at risk and one was affected. No serious adverse event terms are listed. These are the recorded counts; the registry does not provide further event descriptions in the registry record for this summary.

Counts should be read with their denominators. The figures describe events recorded in this small study group, not a comparative estimate against another treatment or a control group. The registry record does not report the timing, duration, severity, or relationship to telmisartan of the other adverse event. It also does not provide enough detail to determine whether all participants were observed for the same duration or whether event collection was complete.

In general, the absence of a recorded serious event in a small study does not establish that serious events cannot occur. Likewise, a recorded event does not establish that the intervention caused it. Without a comparator and detailed event-level information, the figures are descriptive and cannot support a comparative safety assessment.

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

The registry record describes a small, single-group feasibility study of adjunctive telmisartan, with a four-week treatment plan and a primary biomarker endpoint. It identifies the planned comparison within participants over time: baseline blood tumor necrosis factor alpha levels versus levels four weeks after the initial dose. However, the registry record does not report the mean change, its standard deviation, a confidence interval, or an analysis result. The direction and size of the endpoint change therefore cannot be stated.

The record also cannot establish whether telmisartan caused any change. There was no randomized comparator, and the trial was open-label. A change over time, if observed, would be a within-group finding and could not be separated from other possible influences by this design alone. This general limitation applies regardless of whether an estimate is statistically precise.

The stated biomarker hypothesis concerns inflammation and oxidative stress, but the primary endpoint is a blood measure, not a direct report of symptoms or functioning. A biomarker result would need to be interpreted as such; the endpoint definition alone does not show whether a particular amount of change is clinically important. The registry record does not report the numerical result needed to discuss even the biomarker pattern.

The enrollment of six participants and terminated study status provide context, but do not reveal how many participants completed treatment or contributed endpoint data. The reason for termination is not reported in the registry record. Thus, the available information supports a description of the design, treatment schedule, endpoint definition, and recorded adverse-event counts, but not a conclusion about efficacy, the size of a biomarker change, or comparative safety.

Any sample-size planning illustrations are hypothetical calculations under stated assumptions, not evidence about the trial’s outcome or observed power. They do not resolve the absence of an endpoint estimate or create a comparison that the study did not include.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between an endpoint plan and an endpoint result. The registry record specifies a continuous primary measure, its unit, the direction of subtraction, and its follow-up timeframe. Those details define what was intended to be measured. Yet the numerical estimate and its variability are not reported, so readers cannot assess the observed pattern or its precision.

The single-group design also illustrates why the study question must be kept distinct from a comparative treatment question. A within-group change can describe what happened over time among participants with recorded measurements. Without a concurrent control group, it cannot directly answer how those changes compare with what would have occurred under another condition. The open-label design and small enrollment add context to the limits of interpretation.

Planning calculations based on an observed effect can help explore hypothetical future sample sizes, but they are not trial outcomes. In this case, the stated planning assumptions describe a hypothetical two-arm setup that differs from the actual single-group design. The observed effect used as a basis for such illustrations is not reported in the registry record, and a trial-specific sample-size justification is also not reported.

These features make complete outcome and analysis reporting especially important. Information about endpoint estimates, uncertainty, missing data, analysis populations, and the reason for termination would be needed to understand what the study observed and how much can be inferred. The record gives a useful outline of the question and design, while leaving those statistical results and details unreported.

15. 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 key limitation for interpreting this trial is that the registry record does not report the primary endpoint result. It gives no mean change in tumor necrosis factor alpha, standard deviation, confidence interval, or analysis output. The direction, magnitude, and precision of the primary outcome are therefore unknown from the record.

The single-group design has no randomized comparator, and the study was open-label. Any measured change over time would not, by design, isolate a treatment effect from other possible influences. The registry record also does not report further laboratory measurement details, such as assay procedures, or whether laboratory personnel were masked.

The record lists six participants enrolled, but does not report the number who completed treatment or contributed to the primary endpoint. Missing-data methods, analysis populations, adherence, and dose actually received are not described beyond the planned schedule and allowance for dosing as tolerated. The reason the study was terminated is not reported in the registry record. A sample-size justification and details of the statistical analysis plan are also not reported in the registry record.

Finally, four outcome measures are listed, but the record provides zero analysis entries. It does not report how multiplicity was considered or provide enough information to assess whether outcome reporting was complete. These limitations restrict conclusions to the design and recorded counts, rather than the efficacy or precision of the biomarker outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Telmisartan Pilot Study on Treatment Resistant Schizophrenia — NCT03868839.
• Registry record last updated 2022-03-02; status last verified 2022-02.
• Results first posted 2022-03-02.
• 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.

19. Record Summary

NCT03868839 is a phase 2, open-label, single-group feasibility trial of adjunctive telmisartan in people with schizophrenia or schizoaffective disorder whose symptoms had not experienced significant relief from current antipsychotic medication. The planned treatment period was 4 weeks, beginning at 40mg once a day during week 1 and increasing to 80mg, or the dose tolerated, during the remaining three weeks. Six participants were enrolled.

The primary endpoint was mean change in blood tumor necrosis factor alpha, in pg/mL, from baseline to 4 weeks after the initial dose. The study is recorded as terminated, with primary completion on 2020-10-07. The registry record reports zero serious adverse events among six participants at risk, zero deaths, and one other adverse event among six participants at risk. It does not report the primary endpoint result, the reason for termination, or details of missing data and analysis populations.