Plasmodium Vivax Efficacy Trial in Cruzeiro do Sul, Acre, Brazil: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Plasmodium Vivax Efficacy Trial in Cruzeiro do Sul, Acre, Brazil (NCT02043652), a na na study. The primary outcome is Number of Patients With Adequate Clearance of Parasites and Symptoms.

2. Clinical Question

The study addressed the efficacy of chloroquine and primaquine for treating P. vivax malaria in Cruzeiro do Sul. The registry’s background states that malaria treatment policies should be evaluated periodically and that P. vivax is the most common malaria species in Brazil, with cases concentrated in the Amazon Region. Those statements explain the motivation for evaluating the regimen in this setting; they are not results from this study.

The study description also planned to monitor participants for 168 days (6 months) to evaluate possible recrudescence, relapse, or reinfection. A secondary outcome is identified as the number of patients reporting relapses. The registry does not report the observed number for that outcome or explain how those possible events were distinguished in the final analysis.

3. Trial Design

This was a completed, single-group study of treatment for malaria, sponsored by the Centers for Disease Control and Prevention. The registry lists enrollment of 119. The study description planned to enroll at least 117 participants aged 5 years or older with parasitologically confirmed P. vivax monoinfections. The listed start date is 2014-02, and primary completion is listed as 2014-12. The study status is COMPLETED.

There was no randomized allocation and no control arm: allocation is recorded as NA, the model is single group, and the intervention description says all patients would receive the same treatment. Masking is listed as NONE. The phase is listed as NA. These entries describe a treatment-efficacy study without a parallel treatment comparison, rather than a trial designed to estimate a randomized difference between regimens.

The planned regimen was chloroquine for three days at a daily dose of approximately 25 mg/Kg, consistent with Brazilian National Malaria Control guidelines. For patients with normal glucose 6 phosphate dehydrogenase activity, investigators planned to add primaquine at 0.5mg/Kg per day for seven days. The registry does not report how many participants had normal activity or how many received each component in practice.

Clinical and parasitologic parameters were to be monitored during a 28-day follow-up for the primary efficacy assessment, and for 168 days (6 months) to assess possible recrudescence, relapse, or reinfection. Blood samples were planned for chloroquine measurements on Day 7 and, if failure occurred during the initial 28 days, on the day of failure. Filter-paper samples were planned on the first day and on the day of suspected failure to support parasite genotype differentiation using polymerase chain reaction techniques. The registry record does not report whether all planned assessments were completed.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Adequate Clearance of Parasites and Symptoms, measured over 28 days.

The primary endpoint is the number of participants with adequate clearance of parasites and symptoms, assessed over 28 days. It combines parasitologic clearance with symptom clearance: the study description says investigators would evaluate both at regular intervals, following World Health Organization guidelines. The endpoint is recorded as a count of participants, not as a time-to-event measure or as a direct comparison between treatment groups.

Such an endpoint is used to describe whether participants meet a prespecified clinical and parasitologic response criterion during the stated follow-up. Considering symptoms alongside parasitemia can capture more than laboratory status alone, while a defined follow-up period establishes the window in which the response is assessed. These are general features of this kind of endpoint; the registry does not provide the detailed operational definition, visit schedule, or criteria for classifying an individual as having adequate clearance.

The registry identifies the outcome and its 28-day timeframe but does not report the observed count, the denominator used for the outcome analysis, or an uncertainty interval. It also does not state how participants with incomplete assessments or missing parasitology results were handled. As a result, the endpoint’s definition can be described, but the proportion meeting it and the precision of any estimate cannot be determined from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with identifying the outcome type and the study structure. The primary outcome is a count of participants who achieved adequate clearance of parasites and symptoms during a defined follow-up period. This is a binary response for each participant: the response criterion is either met or not met. Summing those participant-level classifications yields a count. In a one-group study, such a count is ordinarily interpreted together with the number of participants whose outcome status was assessed, but the registry does not report that analysis denominator or the observed count.

What does a count communicate?

A count states how many participants met an outcome criterion, but it does not by itself indicate how common the outcome was in the group. A proportion requires both the count meeting the criterion and an appropriate denominator. The denominator might be all enrolled participants or a defined analysis population; the choice affects interpretation and should be explained in the analysis plan or results. The registry record does not report the denominator used for the primary outcome, so an outcome proportion cannot be established from the record.

Precision is a separate issue from the size of an estimate. A confidence interval is a statistical range intended to express uncertainty around an estimate under a specified model and sampling framework. A narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. An interval does not guarantee that the true value lies within its bounds, and it does not resolve possible bias from incomplete follow-up, outcome misclassification, or selection of participants. No confidence interval for the primary result is reported in the registry record.

Why does the single-group design matter?

In a single-group design, outcome summaries describe the participants who receive the study regimen. Without a concurrent comparator, the analysis cannot directly estimate a treatment contrast. General statistical methods for comparing groups require outcomes from distinct groups and a defined comparison; those elements are absent. A favorable or unfavorable count, if one were reported, could not alone establish the counterfactual outcome under another treatment. Differences in patient characteristics, care, or circumstances across separate populations would also complicate indirect comparisons.

The study’s planned clinical and parasitologic follow-up supports an endpoint assessment, but the record does not specify the detailed statistical model or testing procedure. It does not report whether the primary endpoint was analyzed as a count, proportion, or another summary, nor whether any adjustment was used. No p-value or inferential result is listed. The planning significance level described for sample-size illustrations is not evidence that the same threshold was used for an outcome analysis.

What is over-dispersion, and does it apply?

In general, over-dispersion occurs when observed variability in count data exceeds what a chosen statistical model assumes. It can make standard errors too small if the model does not accommodate the extra variability. Whether over-dispersion matters depends on the outcome and analysis model. Here, the primary measure is described as a count of participants meeting a response criterion, rather than a repeated event count or rate. The registry does not report a model or data that would establish whether over-dispersion was assessed, so it should not be assumed to have been present or absent.

Timing is also important. The primary endpoint has a 28-day timeframe, whereas the longer planned follow-up was intended to assess recurrence-related events. A fixed-window response count differs from a time-to-event analysis, which uses the timing of events and may account for differing observation periods. The registry does not report a time-to-event analysis. Its primary endpoint should therefore be understood from the stated count and timeframe, not reinterpreted as a survival estimate.

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. Those are planning assumptions, not a description of this single-group study’s design or an outcome analysis. Such illustrations can show how hypothetical sample-size requirements change under specified assumptions. They are not observed power, do not show that the study had a particular probability of detecting an effect, and do not supply the missing primary result. Any stated sample-size values should be read as participants per arm for 80% power when that is the stated target, rather than as numbers of participants actually observed in a comparison.

Because the registry lists no analyses and no primary outcome result, no recalculation from posted summary statistics is possible. Recalculation would require relevant observed counts and denominators. General statistical principles can clarify what would be needed for interpretation, but they cannot substitute for outcomes that are not reported in the registry record.

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("Chlorquine and Primaquine")
n      <- c(110)
events <- c(110)
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  Chlorquine and Primaquine  110  110  100.0  96.7  100.0  96.6  100.0  96.7  100.0

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies the primary endpoint as the number of participants with adequate clearance of parasites and symptoms over 28 days, and lists the number of patients reporting relapses as a secondary outcome. It also reports two outcome measures overall. The registry does not report a multiplicity strategy, such as a hierarchy among outcomes or an adjustment for testing several outcomes. It also lists no analyses. Therefore, the record does not establish which outcomes were formally tested, whether any testing was planned, or how any resulting p-values would have been interpreted.

Multiplicity is a general concern when several outcomes or comparisons are examined: the chance of at least one apparently noteworthy finding can increase as more tests are conducted. The appropriate response depends on the objectives and prespecified analysis plan. Since the analysis plan and test results are not reported in the registry record, no claim about control of multiplicity or confirmatory status can be made for this study.

Missing-data handling is also not reported in the registry record. The enrollment figure does not establish how many participants had complete symptom and parasitology assessments through the primary follow-up, or how many contributed data to the longer recurrence assessment. The record does not say whether incomplete observations were excluded, treated as failures, imputed, or handled using another approach. Those choices can affect both the count and its denominator.

The primary outcome population is not specified in the registry entry. There is no reported analysis population definition, such as whether all enrolled participants or only those meeting particular assessment criteria were included. The available information therefore does not permit assessment of attrition, deviations from planned follow-up, missing outcomes, or consistency between the intended and analyzed populations.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The safety record lists 119 participants at risk in the serious adverse event category and 119 at risk in the other adverse event category. It records 0 affected participants for each category. These entries describe the registry’s reported counts; they do not provide event narratives, exposure time, or a breakdown by event type. No top serious adverse event terms are listed.

The death count is not reported in the registry record. A blank or unavailable death entry should not be read as a reported zero. Likewise, the listed zeros for serious and other adverse events should be interpreted as the registry’s recorded affected-participant counts, not as proof that every possible safety event was assessed or that none occurred outside the recorded categories.

The record does not describe the adverse-event collection methods, severity grading, attribution process, or completeness of safety follow-up. It also does not report how many participants completed the planned follow-up. These omissions limit interpretation of the safety entries. The numbers do not establish comparative safety because the study had no control arm, and they should not be used to make treatment recommendations.

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

The registry record allows readers to identify the clinical question and planned assessment: a single group was to receive chloroquine, with primaquine for patients with normal glucose 6 phosphate dehydrogenase activity, and investigators planned to assess symptom and parasite clearance over 28 days. The record also describes longer planned follow-up for possible recurrence-related events. These details make the study objective and measurement window understandable.

However, the registry does not report the primary outcome result or the secondary relapse result. It lists no analysis. Thus, the available record does not show how many participants met the primary endpoint, how many were assessed, or how precise any response estimate might be. The missing result cannot be interpreted as a positive finding, a negative finding, or a null effect.

The single-group design further limits what an observed outcome could mean. A reported response count would describe outcomes in the enrolled group, but without a comparator it could not quantify a difference versus another regimen or establish what would have occurred under an alternative. The registry’s design details alone cannot identify a causal treatment effect.

Enrollment is recorded as 119, while the study description planned at least 117 participants. Those figures describe study size and planning, not outcome completion or statistical precision. The registry record does not state the number with complete endpoint data, the analysis population, or the approach to missing observations. The serious and other adverse event entries list 0 affected participants among 119 at risk, while the death count is not reported. These safety entries do not resolve the absent efficacy results.

In short, the record supports a description of study design and intended measurement, but not a conclusion about the observed endpoint or its uncertainty. No medical decision should be inferred from the absence of a result in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why the design and the outcome report must be read together. The registry gives a specific clinical setting, regimen, follow-up schedule, and primary outcome, but the study is single group and has no comparison arm. That means any reported outcome count would answer a descriptive question about participants in that group, not a randomized comparison of treatment strategies.

The outcome definition combines symptom and parasite clearance over 28 days. Such a definition makes clear that the assessment is not solely a laboratory measure or solely a symptom measure. At the same time, interpretation depends on a precise rule for adequate clearance, a transparent denominator, and information about participant follow-up. Those details and the observed result are not reported in the registry record.

The planned 168-day (6 months) follow-up highlights another statistical distinction: short-term clearance and later recurrence are different outcome questions. Recurrence can involve recrudescence, relapse, or reinfection, and the study description proposed blood measurements and genotype procedures to help investigate suspected failure. The registry does not report the findings or final classification of these events, so the planned methods should not be mistaken for results.

The record also illustrates why enrollment alone is not a substitute for an uncertainty estimate. A study’s enrollment figure does not reveal the number with evaluable outcomes or the precision of an estimate. Without the primary count, denominator, and analysis, readers cannot assess the observed response or the extent of sampling uncertainty.

Finally, the reported safety counts need the same careful reading as efficacy outcomes. Registry entries of zero affected participants are specific recorded counts, while the death value is not reported. Neither establishes a comparative safety profile. Statistical interpretation depends on distinguishing what the record documents from what remains unknown.

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 central limitation of the registry record is that it does not report the primary outcome result. The number of participants with adequate clearance of parasites and symptoms, the denominator for that outcome, and any measure of precision are not reported in the registry record. The listed secondary outcome concerning relapse also has no reported result. With no analyses listed, the record cannot support a numerical assessment of efficacy or uncertainty.

The single-group design has no like-for-like control comparison. Even if outcome results were available, they would describe the group treated under the study conditions and would not directly estimate a contrast against an alternative regimen. Allocation is listed as NA and masking as NONE. The registry does not report a detailed protocol or statistical analysis plan, so further design assumptions should not be inferred.

Important information about completion and analysis is absent. The registry does not report how many participants completed each follow-up period, how many had missing symptom or parasitology assessments, which participants entered the endpoint analysis, or how missing outcomes were handled. It also does not provide detailed criteria for adequate clearance or for classifying later events as recrudescence, relapse, or reinfection.

The study description includes planned drug-level and genotype assessments, but their results are not reported in the registry record. Adverse-event entries list zero affected participants in the serious and other categories, while the death count is not reported; the record does not describe safety ascertainment or follow-up completeness. These limitations restrict both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Plasmodium Vivax Efficacy Trial in Cruzeiro do Sul, Acre, Brazil — NCT02043652.
• Registry record last updated 2018-02-07; status last verified 2014-01.
• Results first posted 2018-02-07.
• 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

NCT02043652 is a completed, single-group study sponsored by the Centers for Disease Control and Prevention. It examined chloroquine and primaquine for P. vivax malaria in Cruzeiro do Sul, Acre, Brazil. Enrollment is listed as 119; the description planned to enroll at least 117 participants aged 5 years or older. The listed study dates are 2014-02 for start and 2014-12 for primary completion.

The primary endpoint was the number of participants with adequate clearance of parasites and symptoms over 28 days. Planned follow-up for possible recurrence extended to 168 days (6 months). The registry record does not report the primary or secondary outcome results and lists no analyses. There was no comparison arm. Serious and other adverse event entries each record 0 affected participants among 119 at risk; the death count is not reported in the registry record.