Safety and Efficacy Study of IV Artesunate to Treat Malaria: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of IV Artesunate to Treat Malaria (NCT00298610), a na phase 2 study. The primary outcome is Change in Percentage of Parasites Detected at 48 Hours.

2. Clinical Question

The study description identifies two related aims: to characterize how intravenous artesunate is metabolized and cleared in people with uncomplicated malaria, and to determine how quickly it eliminates malaria infection from the body. The listed primary endpoint addresses parasite change at a specified time after dosing. Secondary outcomes include percentage of parasite clearance, fever clearance, and adverse-event measures.

Because everyone in the listed group received artesunate and then Malarone, the registry record cannot establish how the observed course compares with an untreated group or with a group receiving a different initial treatment. The treatment sequence also means that later observations may reflect more than the artesunate course alone. The record does not report detailed outcome timing beyond the stated primary timeframe and the named secondary outcomes.

3. Trial Design

This is a Phase II, open-label study with a single-group design. The registry lists an enrollment of 30 and describes adults with uncomplicated malaria. Allocation is recorded as not applicable, and masking as none. There is no separate randomized control arm in the study description.

Participants received intravenous artesunate once a day for 3 days. After completing artesunate, all subjects received Malarone follow-on therapy, which the registry description says was intended to ensure parasitologic cure. Thus, the intervention is a treatment sequence rather than an isolated comparison of artesunate against another assigned regimen.

The primary endpoint is change in percentage of parasites detected at 48 hours. Secondary outcomes cover parasite clearance, fever clearance, and safety, including adverse-event severity and the recorded relationship of adverse events to study drug. The registry lists 7 outcome measures but reports 0 analyses. Numerical results for the primary endpoint and the listed secondary outcomes are not reported in the registry record.

The study is marked completed. Its start is recorded as 2006-03, and primary completion as 2007-10. The sponsor is the U.S. Army Medical Research and Development Command. Further design details—including the eligibility criteria, recruitment setting, follow-up schedule, and procedures for measuring parasite burden—are not reported in the registry record.

A single-group design can describe what was observed among participants receiving the treatment sequence, but it does not isolate the effect of artesunate from other influences. Without a concurrent comparator, changes may also reflect the course of the illness, participant characteristics, measurement procedures, or other care. The registry record does not report a protocol or statistical analysis plan that would clarify how the investigators intended to address such factors.

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: Percentage of parasite change at 48 hours post dose

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 Change in Percentage of Parasites Detected at 48 Hours, measured over 48 hours.

The primary endpoint is titled “Change in Percentage of Parasites Detected at 48 Hours.” It is a continuous measure summarized as a mean with a standard deviation. The registry description defines positive values as increases and negative values as decreases in the percentage of parasites detected. The stated timeframe is 48 hours, and the endpoint population is described as percentage of parasite change at 48 hours post dose.

Parasite change is relevant to the study’s stated aim of assessing how quickly artesunate eliminates malaria infection from the body. A measure at a defined time after dosing can describe the direction and size of change over that interval. It is distinct from a direct comparison of treatment groups: this study lists only one group, and therefore the endpoint does not estimate a between-group difference.

The record does not report the numerical mean, standard deviation, number of participants contributing endpoint data, or a confidence interval. It also does not specify the precise reference value used to define the change, the measurement method, or how missing endpoint measurements were handled. Without those details and the numerical result, the magnitude and precision of the observed change cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a continuous primary measure and says it is summarized as a mean and standard deviation. It does not report the primary outcome values or the analysis procedures used to produce them. The explanations below describe general statistical concepts; they do not imply that any particular method was used in this study.

What does a mean describe?

General: A mean is an average across the observations included in an analysis. For a continuous endpoint such as parasite percentage change, it gives a compact description of the center of the measured values. Its interpretation depends on what was measured, how change was defined, and which participants had usable measurements. The registry record names the endpoint but does not report the endpoint mean or an outcome-specific participant count.

A mean can conceal differing patterns among participants. Similar averages can arise when most participants have similar values or when individual values vary substantially in opposite directions. The standard deviation helps describe spread around the mean, but it is not a measure of the uncertainty in the mean itself. The registry names standard deviation as the dispersion measure, but the numerical standard deviation is not reported in the registry record.

What would a confidence interval add?

General: A confidence interval expresses uncertainty around an estimated quantity under a statistical model and its assumptions. For a mean, it can help readers judge whether the estimate is precise or compatible with a broad range of values. It does not make a single-group design comparative, and it does not remove possible measurement or selection biases. No confidence interval is reported for the primary endpoint in the registry record.

Precision is affected by the amount of information in the data and by how variable the measurements are. A small standard error or narrow interval, when properly calculated, indicates greater precision for the estimated quantity; it does not establish that the estimate is unbiased or that the treatment caused the observed outcome. The registry record does not provide the numerical data needed to describe precision for this endpoint.

Why does the single-group design matter?

General: A comparison group can help distinguish changes associated with an intervention from changes that might occur without it, provided the design and analysis support a fair comparison. This study is listed as single-group, with allocation not applicable and no masking. Its recorded treatment sequence includes artesunate followed by Malarone. Therefore, the primary endpoint can describe change in the study group, but a treatment contrast against a concurrent control is not available from the described design.

Open-label means that masking is recorded as none. In general, knowledge of treatment can affect some measurements, assessments, or reporting, depending on the outcome and procedures. The registry record does not provide enough detail to assess whether or how this could have influenced the parasite measurement or the secondary outcomes.

What can planning calculations say?

General: Sample-size calculations estimate how much information a future design might need under specified assumptions. They are planning illustrations, not observed results and not a measure of the evidence collected in a completed study. The registry’s planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm.

Those assumptions do not describe the recorded study design, which is single-group and has no randomized two-arm comparison. The registry record does not report a sample-size justification for the trial itself. Nor does it report the observed primary effect needed to interpret any planning illustration in terms of this endpoint. Such calculations should therefore be kept separate from the trial’s actual enrollment and from evidence about the treatment sequence.

Why can over-dispersion matter?

General: Over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, standard errors and confidence intervals may be too small, and tests may appear more conclusive than warranted. This concept matters when a chosen model relies on a particular variance structure. The registry identifies a continuous mean endpoint and standard deviation, but it does not report a model, a variance assumption, or an assessment of over-dispersion. It would not be appropriate to claim that over-dispersion was present or addressed in this trial.

Overall, the posted record permits a description of the outcome definition, study structure, and stated summary measure. It does not provide the numerical endpoint result, inferential estimates, or enough analysis detail to evaluate the statistical method used. These gaps limit any assessment of effect size, precision, and robustness.

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("Artesunate and Malarone")
n   <- c(30)
m   <- c(99.998)
sp  <- c(0.0006)
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  Artesunate and Malarone  30  99.998  0.001  99.998  99.998

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including the primary parasite-change endpoint and secondary measures of parasite clearance, fever clearance, and safety. When a study assesses several outcomes or makes several statistical comparisons, the chance of at least one apparently unusual result can increase. General approaches to multiplicity include prespecifying a primary outcome, adjusting inference across selected tests, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy or identify any completed statistical analyses; it lists 0 analyses.

The registry record does identify a primary endpoint, but it does not report a numerical result, confidence interval, p-value, or detailed analysis plan for that endpoint. Results for the secondary outcomes are also not reported in the registry record. It is therefore not possible to determine whether outcome testing was adjusted, prioritized, or interpreted as exploratory.

Missing-data handling is not reported in the registry record. The enrollment figure does not establish how many participants contributed measurements to each endpoint. The record does not state whether participants withdrew, whether endpoint measurements were unavailable, how missing observations were handled, or whether a particular analysis population was used. These details matter because an analysis based only on participants with observed outcomes can differ from one that uses another prespecified approach, especially if missingness is related to outcomes or treatment experience.

The registry also does not report whether analyses followed an intention-to-treat, per-protocol, or other population definition. Without these details, the relationship between the enrolled group and the participants included in each result cannot be assessed. No conclusion about the presence, amount, or effect of missing data can be drawn from the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stevens-johnson syndrome (3.3%).

The registry lists 30 participants at risk for serious adverse events and records 1 in the serious adverse-event count. It also lists 30 participants at risk and 30 in the other adverse-event count. These are safety entries for the Artesunate and Malarone group; they are not comparisons with a separate control group. The record identifies Stevens-Johnson Syndrome as the top serious term, with 3.3% listed.

These figures should be read as recorded safety counts, not as proof of cause. The study included both artesunate and follow-on Malarone, and the registry also lists outcomes concerning the relationship of adverse events to study drug. Results for those relationship assessments are not reported in the registry record. The figure for a serious event therefore does not, by itself, establish whether the event was attributed to either drug.

The deaths value is not reported in the registry record. Further details such as event timing, clinical course, and the number of distinct events versus affected participants are not reported in the registry record. With no comparator group, the listed counts cannot show whether event frequency differs from another treatment or from an untreated course.

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

The registry record establishes that a Phase II, open-label, single-group study enrolled 30 adults with uncomplicated malaria and used intravenous artesunate once a day for 3 days, followed by Malarone. It defines the primary endpoint as change in percentage of parasites detected at 48 hours, with positive values indicating an increase and negative values indicating a decrease. These details describe the study question and treatment sequence.

The registry does not report the numerical primary endpoint result. As a result, the posted record does not establish the average parasite change, the variability among participants, or the precision of an estimate. It also does not report inferential analyses for the endpoint. The outcome definition alone cannot say how large a change was observed or how uncertain it was.

Even a numerical result from a single group would describe outcomes during the recorded treatment sequence, not a causal contrast against another regimen. There is no concurrent randomized comparator listed, and Malarone followed artesunate. Any later outcome could reflect the sequence as a whole or other influences; the registry information does not isolate the effect of artesunate.

The safety entries provide counts for adverse-event categories and identify a serious-event term. They do not establish causation or comparative safety. Relationship-specific results are not reported in the registry record. The record also does not report the details needed to judge outcome completeness, analysis populations, or the handling of missing measurements.

Accordingly, the registry supports a concise description of the trial’s design, intended outcomes, and some safety counts. It does not support a quantitative conclusion about the primary endpoint, a between-treatment comparison, or an assessment of statistical precision. These distinctions are important when interpreting a completed study whose outcome analyses are not posted in the registry record.

14. Why This Trial Matters Statistically

This study illustrates a central distinction in clinical trial interpretation: an outcome definition is not an outcome result. The registry specifies a continuous measure of parasite change at 48 hours and the direction assigned to positive and negative values. Without the numerical mean, standard deviation, or an uncertainty interval, readers cannot judge the observed magnitude or precision.

Its single-group design also makes the estimand important. The study describes outcomes among participants receiving artesunate followed by Malarone, rather than a randomized contrast between treatment options. An observed within-group change, if reported, would not by itself reveal what would have happened to comparable participants under a different regimen or without the same sequence.

The record provides an opportunity to distinguish trial planning from trial evidence. The stated sample-size assumptions describe an illustration for a two-arm design using equal allocation and a normal approximation. That is conceptually different from the listed single-group design and cannot be treated as observed power or as a justification for the actual enrollment. The record does not report the trial’s own sample-size justification.

Finally, the gap between listed outcomes and reported analyses matters. The registry names primary and secondary safety and efficacy measures but lists 0 analyses. This makes it especially important not to infer results from titles, design descriptions, or a small number of safety entries. In statistical reading, knowing what was intended to be measured is useful, but it is not a substitute for estimates, uncertainty, and transparent analysis details.

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 chief limitation for interpreting this specific record is that it does not report numerical results for the primary endpoint. The mean and standard deviation are named as the summary approach, but their values are absent. No confidence interval, p-value, or other inferential result is reported in the registry record, which lists 0 analyses.

The trial is recorded as a single-group, open-label study with no randomized comparator. The described intervention includes artesunate followed by Malarone, so the design does not separate the contribution of the initial treatment from the full sequence or from changes over time. The registry does not report enough detail to assess the measurement process or possible influence of open-label assessment.

Enrollment is listed as 30, but outcome-specific denominators and analysis populations are not reported in the registry record. Missing-data procedures, eligibility details, baseline characteristics, follow-up procedures, and the statistical analysis plan are also not reported in the registry record. These omissions prevent a detailed assessment of completeness, comparability, and analytic choices.

Safety information is limited to the listed counts and top serious term. The record does not report the deaths value, detailed event descriptions, or results of the listed drug-relationship assessments. Because there is no separate comparator group, the safety entries cannot support a comparative estimate. Finally, the registry’s planning assumptions concern a two-arm illustration, whereas the recorded trial is single-group; the record does not report the trial’s own sample-size justification.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of IV Artesunate to Treat Malaria — NCT00298610.
• Registry record last updated 2019-10-01; status last verified 2016-11.
• Results first posted 2017-03-22.
• 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

NCT00298610 is a completed Phase II, open-label, single-group study titled “Safety and Efficacy Study of IV Artesunate to Treat Malaria.” It lists 30 enrolled adults with uncomplicated malaria. Participants received intravenous artesunate once a day for 3 days, followed by Malarone.

The primary outcome is change in percentage of parasites detected at 48 hours, summarized as a mean with standard deviation; positive values indicate increases and negative values indicate decreases. The registry lists 7 outcome measures and 0 analyses. The numerical primary result and results for the named secondary outcomes are not reported in the registry record.

The safety record lists 1 serious adverse-event count among 30 at risk, 30 in the other adverse-event count among 30 at risk, and Stevens-Johnson Syndrome as the top serious term at 3.3%. The deaths value is not reported in the registry record. No separate randomized comparator is listed, so the record does not provide a like-for-like treatment comparison.