Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke Before and After Thrombectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke Before and After Thrombectomy (NCT04061577), a randomized na study. The primary outcome is Primary Safety Outcome- Number of Participants With Symptomatic Intracranial Hemorrhage (SICH).

2. Clinical Question

The study was designed to examine the safety, tolerability and feasibility of transcranial direct current stimulation (tDCS) in acute ischemic stroke, with potential efficacy also identified as an area of interest. The registry describes patients with a large vessel occlusion and substantial salvageable penumbra who were treated before and after endovascular therapy.

The question is principally one of early safety in a clinical setting where endovascular treatment is also part of care. The registry identifies a randomized design and a planned active-to-sham allocation ratio of 3:1, but the record’s actual arm counts show enrollment only in the active arm. Therefore, the planned contrast cannot be evaluated from the posted results. The record does not establish whether stimulation changed hemorrhage risk, nor does it provide an estimate of potential efficacy.

3. Trial Design

The registry describes a prospective, randomized, single-center, sequential, dose-escalation study. It was sponsored by the University of California, Los Angeles, and listed as terminated. The recorded start date is 2019-07-28, and the primary completion date is 2022-04-01. The primary outcome description states that the study stopped early after the enrollment of the first patient.

The intervention was transcranial direct current stimulation, classified in the registry as a device. The study description frames stimulation as a possible neuroprotective approach around endovascular therapy in acute stroke. Active treatment was to be compared with sham in a 3:1 ratio, and the design included six dose tiers. The available arm description gives examples for Tier 1 at 1 mA and Tier 2 at 2 mA: each is described as a single stimulation cycle lasting 20min after the endovascular procedure for patients meeting specified clinical conditions. The description of those conditions is incomplete in the registry record, so it does not support a fuller account of eligibility at each tier.

For sham stimulation, the cap and electrodes were to be placed and the sham switch moved, without electrical stimulation. Masking is recorded as single, but the registry does not identify who was masked. The record does not report the randomization sequence method, allocation concealment procedures, or how dose escalation decisions were to be made.

The registry lists enrollment as 1. The posted arm data list one participant in the active stimulation arm and no participants in the sham arm. This does not match the planned allocation ratio in a way that permits an active-versus-sham assessment. The registry does not explain why enrollment stopped, whether the termination was related to an event, or whether the dose-escalation sequence advanced. Those details 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

Analysis population for the primary outcome, as defined in the registry: The study was stopped early after the enrollment of the first patient.

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 was stopped early.

6. Primary Endpoint

The registry lists the primary outcome as Primary Safety Outcome- Number of Participants With Symptomatic Intracranial Hemorrhage (SICH), measured over At 24-hour post-stimulation.

The primary safety outcome is the number of participants with symptomatic intracranial hemorrhage (SICH), assessed at 24-hour post-stimulation. The registry defines SICH as an increase of 4 or more points on the National Institute of Health Stroke Scale (NIHSS) total score within 24 hours of stimulation, associated with a listed hemorrhage type: parenchymal hematoma type 1 (PH1), parenchymal hematoma type 2 (PH2), remote intraparenchymal hemorrhage (RIH), subarachnoid hemorrhage (SAH), or intraventricular hemorrhage (IVH).

The NIHSS is a structured neurologic examination used to evaluate stroke-related impairment, including consciousness, language, visual-field loss, movement, strength, coordination, speech and sensation. The registry describes a possible total score from 0 to 42, with higher scores indicating greater impairment. The endpoint therefore combines a worsening in neurologic examination with evidence of intracranial bleeding; it is not simply a count of any hemorrhage.

This endpoint is used as a safety measure because it captures clinically consequential bleeding accompanied by neurologic deterioration in a defined time window after stimulation. The posted result lists zero participants with SICH in the active arm and zero in the sham arm. However, no participant is listed in the sham arm, so its zero count does not provide evidence about the outcome risk under sham. The endpoint definition and counts do not establish whether any event was caused by stimulation or by other aspects of acute stroke care.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as randomized and sequential, with a single-center dose-escalation structure. Randomization is intended to reduce systematic differences between groups by assigning participants using a chance-based process. In a completed trial with participants in each arm, it can support a fair comparison of outcomes, subject to adequate conduct and analysis. Here, the posted arm data list one participant in the active arm and no participants in the sham arm. Randomization cannot create a comparison when one arm has no enrolled participants, so the design intention should not be confused with an estimable treatment effect.

What does the primary count represent?

The primary endpoint is a binary event outcome expressed as a count of participants meeting the SICH definition. A participant either meets the recorded definition during the stated observation window or does not. The outcome is not a continuous measurement of bleeding severity, and the registry does not report individual NIHSS scores or event-level details. A count alone is most interpretable alongside the number of participants observed in each arm and the completeness of follow-up. The sham arm has no participants listed, so its zero count cannot be treated as an observed rate among sham-treated participants.

Why is a comparative estimate unavailable?

Comparative statistics require information from the groups being compared. A difference between group risks, a relative risk, or an odds ratio would rely on a meaningful numerator and denominator for each arm. With no sham participants listed, the sham outcome risk is not estimated from observed participants. A confidence interval would express uncertainty around an estimated quantity, but the registry does not report one, and the posted arm data do not permit a useful two-arm estimate. The registry explicitly indicates that values are missing or not estimable for a two-arm comparison of this binary endpoint. No recalculated comparison is presented.

In general, a p-value assesses how compatible observed data are with a specified statistical model under a null hypothesis; it does not measure the size or clinical importance of an effect. The record lists no analyses and reports no p-value for the primary endpoint. In general, a confidence interval conveys the range of effect values reasonably compatible with data and assumptions. No such interval is reported for this outcome. Neither statistic can repair the lack of an enrolled comparison group.

What does dose escalation add?

A dose-escalation design evaluates successive dose levels, usually with attention to safety and tolerability as exposure increases. The registry describes six dose tiers, a sequential model, and active stimulation compared with sham. The arm descriptions identify 1 mA and 2 mA tiers, including a single 20min post-procedure stimulation cycle in specified circumstances. The record does not report the operational rules for moving between tiers, the outcomes by tier, or whether escalation proceeded. It therefore cannot show how safety varied by dose or establish a dose-response pattern.

The registry’s masking designation is single. Masking can reduce the influence of expectations on participant experience, outcome assessment, or both, depending on who is masked and how procedures are implemented. The record does not identify the masked party or describe masking checks. It does describe the sham procedure as placing the cap and electrodes and moving the sham switch without delivering electrical stimulation. No claim about the success of masking can be made from the record.

How should planning calculations be read?

In general, sample-size calculations describe how many participants might be needed to detect a chosen effect under specified assumptions. They are planning illustrations, not observed power and not a retrospective measure of whether a completed trial was adequately powered. The registry’s planning assumptions refer to a two-sided significance level of 0.05, equal allocation, a normal approximation, and fractions of an observed effect. Those assumptions do not turn the posted counts into an estimable comparison. The record indicates that values are missing or not estimable for a two-arm binary comparison, and no planning sample-size figures are available in the posted outcome information. The study’s planned 3:1 allocation is distinct from the equal-allocation assumption used for the planning illustration.

For binary outcomes, sparse data and zero counts can make standard approximations unreliable or impossible to apply. In general, methods for rare events may require exact procedures, suitable modeling assumptions, or more information than a single-arm observation provides. No such method or analysis is reported in the registry record. No statistical analysis plan, prespecified model, interim analysis approach, or multiplicity procedure is reported. Accordingly, the most defensible reading is descriptive: the posted active-arm SICH count is zero, the sham arm has no enrolled participant, and comparative uncertainty cannot be quantified from the registry results.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Active Stimulation Arm")
n      <- c(1)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Active Stimulation Arm  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, including the primary SICH safety outcome and secondary safety outcomes for asymptomatic intracranial hemorrhage, early neurologic deterioration, mortality, and all serious adverse events, anticipated and unanticipated. It lists no analyses. A list of outcomes does not establish which outcomes were formally tested, how they were prioritized beyond the primary designation, or whether any statistical adjustment for multiple comparisons was planned. Such a multiplicity strategy is not reported in the registry record.

When multiple outcomes are tested, the chance of at least one apparently notable result can increase if each is interpreted without accounting for the collection of tests. In general, a prespecified hierarchy or adjustment can address this issue, but the record does not report one. Given the very early stop and the absence of an enrolled sham participant, the registry results do not support a set of comparative tests across primary and secondary outcomes.

Details about missing outcome data, withdrawals, follow-up completion, and the handling of unavailable measurements are not reported in the registry record. The primary outcome description states that the study stopped early after enrollment of the first patient, but it does not provide a participant flow account or specify analysis populations. The record does not state whether an intention-to-treat, per-protocol, or safety population was defined or used. The available arm listing records one active participant and none in sham; this makes the comparison unavailable regardless of the analysis population label. No missing-data method or sensitivity analysis is reported.

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 serious adverse event terms

Serious events with the highest arm-level rate: anticipated serious adverse events (100.0%), unanticipated serious adverse event (0.0%).

The serious adverse-event listing reports one participant at risk and one affected participant in the active stimulation arm. It lists no participants at risk or affected in the sham arm. It also reports one death in the active arm and none in the sham arm. The sham-arm entries should not be interpreted as observed event-free follow-up because the arm has no participants listed. The active-arm entries are descriptive counts and do not, by themselves, establish cause.

The registry’s serious-event terms list anticipated serious adverse events at 100.0% and an unanticipated serious adverse event at 0.0%. These categories should be read as the posted registry classifications; the record does not provide enough detail to infer the event’s clinical course, timing, or relation to stimulation. In particular, the death entry does not establish that stimulation caused the death, and the serious adverse event entry should not be assumed to be the primary SICH outcome.

Safety counts may refer to different definitions and observation rules. They should not be added together or treated as interchangeable measures. The record gives no comparative safety estimate, and a zero count in an arm with no participants does not demonstrate absence of risk. The available information supports only a limited description of the recorded counts and categories.

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

The posted results document an early-terminated study with enrollment of the first patient only. The primary outcome listing records zero participants with symptomatic intracranial hemorrhage in the active arm and zero in the sham arm, while the arm data list one participant in active stimulation and no participants in sham. The result therefore describes an observation in the active arm but does not provide a populated comparator. It cannot show whether SICH was more or less frequent with active stimulation than with sham.

These data do not establish that tDCS prevents hemorrhage, reduces neurologic deterioration, or improves stroke outcomes. The registry identifies safety, tolerability, feasibility, and potential efficacy as study aims, but the posted information does not provide comparative efficacy analyses. Nor does the zero active-arm SICH count establish that stimulation is free of risk. Rare or variable safety outcomes cannot be characterized confidently from this record’s limited enrollment.

The safety listings also should not be used to attribute the recorded serious adverse event or death to stimulation. The registry does not report a causal assessment, detailed event narratives, timing, or relevant clinical context. A temporal association, even if known, would not alone establish causation; in this record, the necessary detail is not reported.

More broadly, the trial’s planned randomized and dose-escalation design is not equivalent to evidence that those comparisons were completed. The record does not report progression through dose tiers or outcomes by tier. It also does not report an analysis plan, confidence intervals, or inferential tests. The conclusions must remain descriptive and specific to the posted record: enrollment ended very early, the active arm has a zero SICH count, and a sham comparison cannot be made.

This is not a basis for individual treatment decisions. It is a record of a study’s status and its limited posted outcome information. Readers should distinguish the study’s intended questions from the questions the available data can answer. The intended comparison and safety assessment are not resolved by these results.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a planned randomized comparison and an analysis supported by observed data. The registry describes randomization, sham control, and a 3:1 intended allocation, but the posted arm data contain no sham participant. A control group is essential to estimating what might have happened under the alternative intervention; without observed participants in that group, the trial cannot estimate the planned contrast.

It also highlights the limits of a zero event count. A zero count in an arm with an observed participant is a fact about the recorded follow-up, not a guarantee that the underlying event risk is zero. A zero count in an arm with no listed participants is not an observed event rate at all. Treating both as equivalent would obscure the distinction between no event observed and no opportunity for observation.

The sequential dose-escalation format adds another interpretive challenge. Safety findings can depend on dose and treatment context, but the registry does not report whether escalation proceeded or provide outcomes by tier. Thus, the design’s potential to describe tolerability across dose levels is not realized in the posted results.

Finally, the case underscores why precision and uncertainty matter in safety reporting. Counts without a usable comparison, uncertainty interval, or analysis cannot quantify comparative risk. The statistical lesson is not that the intervention is safe or unsafe; it is that the registry record does not contain enough comparative information to answer that question. Transparent reporting of enrollment, denominators, outcome definitions, analysis methods, and reasons for early termination is important for readers assessing what a small or stopped trial can establish.

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 main limitation is the very limited enrollment: the primary outcome description says the study stopped early after enrollment of the first patient, and the posted arm data list one participant in active stimulation and none in sham. This prevents estimation of the planned active-versus-sham contrast. The available SICH counts cannot support comparative risk estimates or reliable conclusions about safety.

The registry does not report why the trial was terminated, whether the termination was planned or prompted by a safety, operational, or other consideration, or whether the study advanced beyond an initial dose tier. Those reasons must not be inferred from the status alone. The record also does not provide outcome data by dose tier, detailed participant characteristics, or an account of follow-up completeness.

Several design and analysis details are not reported in the registry record: the randomization method, allocation concealment, identity of the party masked, dose-escalation rules, statistical analysis plan, handling of missing data, analysis populations, and procedures for multiple outcomes. No p-values, confidence intervals, or comparative estimates are reported. These omissions limit evaluation of both the intended methods and any potential bias.

The serious adverse-event and death listings lack event narratives and causal assessments. The record does not establish whether those entries relate to stimulation, the stroke, endovascular therapy, or another circumstance. The SICH definition is specific, but the registry does not provide case-level information to independently assess its application. Overall, these limitations mean the registry supports only a narrow descriptive reading, not a treatment-effect conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke Before and After Thrombectomy — NCT04061577.
• Registry record last updated 2023-07-20; status last verified 2023-06.
• Results first posted 2023-07-20.
• 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

NCT04061577 is a randomized, single-center, sequential dose-escalation study of transcranial direct current stimulation around endovascular therapy for acute ischemic stroke. The registry describes active stimulation and sham, with six dose tiers and a planned 3:1 allocation. The study is listed as terminated, and the primary outcome description says it stopped early after enrollment of the first patient.

The primary safety outcome is the count of participants with SICH at 24-hour post-stimulation. The posted results list zero in the active arm and zero in the sham arm, but the arm data show no participant in sham. The registry also lists one serious adverse event and one death in the active arm; it does not establish causality. No analyses are listed, and a comparative effect cannot be estimated from the posted arm data. Reasons for termination and several analysis details are not reported in the registry record.