Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy (Phase 2): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy (Phase 2) (NCT05406479), a randomized phase 2 study. The primary outcome is Mean Difference in QTc Interval Between the Two Arms 24 Hours After Treatment Administration.

2. Clinical Question

The main statistical focus is a short-term safety comparison, rather than a reported estimate of prophylactic efficacy. QTc interval is the continuous endpoint specified for the primary comparison, and the analysis is framed as a difference in arm means. The registry record identifies the trial as phase 2 and describes the study as a safety study preceding a main study. It does not report a numerical QTc result, so the direction, magnitude, and precision of the between-arm difference cannot be assessed from the registry results.

3. Trial Design

The registry identifies BE-PEOPLE as a phase 2 randomized, open-label, parallel-group study. Its recorded enrollment is 313, and its status is completed. The recorded study start is 2022-07-14, and the primary completion date is 2023-01-26. The sponsor is the Institute of Tropical Medicine, Belgium.

The comparison is between BE-PEP, described as bedaquiline post-exposure prophylaxis with rifampicin, and SDR-PEP, described as single-dose rifampicin post-exposure prophylaxis. The record says eligible participants in the BE-PEP arm received one dose of bedaquiline plus rifampicin; participants in the SDR-PEP arm received one dose of rifampicin. The registry summary also discusses a planned regimen involving weight-dependent bedaquiline dosing and a repeat dose after four weeks for household contacts. The record does not fully explain how that broader description maps onto the phase 2 safety study's treatment administration.

Randomization supports a comparative design, but masking is listed as none. The registry record does not report details of sequence generation, allocation concealment, or the handling of deviations from assigned treatment. Those details should not be inferred from the design labels alone.

The primary endpoint is a mean difference in QTc interval 24 hours after treatment administration, with the contrast defined as BE-PEP minus SDR-PEP. The stated population is participants included per protocol. Although the record gives enrollment, it does not report the number analyzed for this endpoint or the numerical endpoint result. It also does not report detailed baseline characteristics, the distribution of participant types across arms, or the full protocol. The study is marked completed, but completion status alone does not establish that every planned analysis or outcome is available 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: participants included per protocol

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: All randomized participants

6. Primary Endpoint

The registry lists the primary outcome as Mean Difference in QTc Interval Between the Two Arms 24 Hours After Treatment Administration, measured over 24 hours after treatment administration.

The primary endpoint is the mean difference in QTc interval between BE-PEP and SDR-PEP 24 hours after treatment administration. QTc is an electrocardiographic interval adjusted for heart rate; the registry specifies the measure in milliseconds and defines the contrast as BE-PEP minus SDR-PEP. The endpoint is reported as a continuous measure, and the stated analysis population is participants included per protocol.

In general, a continuous endpoint can capture differences across the full range of measured values rather than reducing the information to a yes-or-no event. A between-arm mean difference describes the separation between the average values in the groups, while a confidence interval communicates uncertainty around that estimate. The clinical interpretation depends on the estimate's size, direction, precision, and relevant context.

QTc is relevant to a safety assessment because changes in this interval can be monitored after treatment administration. This general rationale does not establish that any treatment caused a change in this study. The registry record does not report the observed mean difference, the confidence interval limits, or the arm-specific QTc summaries. Therefore, the endpoint's direction and precision cannot be described from the posted results. The 24-hour timeframe also identifies a specific measurement window; it does not, by itself, describe later QTc measurements or longer-term safety.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry defines the target contrast as a mean difference. In general, a mean difference subtracts the average value in one arm from the average value in another. Here the direction is explicitly BE-PEP minus SDR-PEP. A positive estimate would indicate a higher mean QTc in BE-PEP relative to SDR-PEP, while a negative estimate would indicate a lower mean, if the estimate were reported. The registry record does not report that estimate, so neither direction applies as a description of the observed trial result.

The specified uncertainty measure is a 95% confidence interval. In general, a confidence interval gives a range of values compatible with the data and the statistical procedure used, under its assumptions. It is not a guarantee that the true value lies within the interval, nor does it by itself determine whether a difference is important. Interpretation would consider the point estimate, interval width, and the context of the measurement. The record does not give the interval limits for the primary QTc comparison.

The primary endpoint is measured 24 hours after treatment administration, and its population is participants included per protocol. A per-protocol analysis generally focuses on participants who meet specified criteria for adherence or eligibility for the analysis. The exact criteria are not reported in the registry record. Per-protocol results can be useful for describing outcomes among participants analyzed according to such criteria, but exclusions from that population can affect how well the comparison preserves the benefits of randomization. The registry does not report the number contributing to the endpoint analysis or the reasons participants may have been excluded.

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance and aims to balance prognostic factors across groups. It does not guarantee identical groups in every respect, especially in a particular trial. This study is labeled randomized and parallel, but the registry record does not describe the sequence-generation method, allocation concealment, or implementation details. The record lists no masking. Open-label status means that masking is not reported as part of the design; the record does not give further information about who knew assignments or how outcome measurement was conducted.

How should adverse-event counts be read?

The registry reports affected counts and at-risk counts by arm for serious and other adverse events. These are descriptive summaries, not a reported comparative model. In general, a count gives the number recorded under the specified outcome definition, while the at-risk count describes the group denominator listed for that outcome. The record does not explain whether events were counted once per participant, how recurrent events were handled, or whether follow-up exposure differed between groups. It also does not report a statistical test or confidence interval for the adverse-event comparisons. These details matter because raw counts alone do not convey uncertainty or account for possible differences in observation time.

What can be inferred from the planning assumptions?

The registry record includes a general description of a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are assumptions for an illustrative calculation, not evidence about the trial's observed power and not a description of the trial's original design rationale. Numerical planning outputs are not reported in the registry record, and the record does not give the original sample-size justification. No sample-size conclusion can therefore be drawn from those assumptions alone.

In general, power calculations estimate the chance that a specified statistical procedure will detect an effect under assumed conditions. They depend on the target effect and other design assumptions. A retrospective calculation based on an observed effect should not be interpreted as proof that a study was adequately powered, and it does not replace reporting the estimate and its uncertainty.

What analysis details remain unknown?

The registry record notes two outcome measures and three analyses, but does not give enough detail to determine how those analyses relate to one another, whether they include multiple time points, or which statistical procedures were used. The record does not report model covariates, assumptions checks, handling of missing data, or multiplicity adjustment. The primary outcome is not reduced to a single comparison in the posted analysis details. Without the numerical result and analysis specification, recalculation or evaluation of the sponsor's analysis is not possible from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record notes two outcome measures and three analyses. It does not report the full set of analysis questions, how the analyses relate to the outcome measures, or whether any adjustment for multiple comparisons was planned or used. Because multiple analyses can increase the chance of at least one apparently unusual result when considered together, multiplicity procedures may be relevant in general. The available record does not establish whether that issue was addressed, so no claim about adjustment or its absence in the study's actual analysis is warranted.

The primary endpoint population is described as participants included per protocol. The number analyzed for the primary endpoint, the reasons for any exclusions, and the criteria defining the per-protocol set are not reported in the registry record. An intention-to-treat analysis is not reported in the registry record. The record also does not state how missing QTc measurements were handled, whether missingness differed between arms, or whether any sensitivity analysis was performed.

In general, missing outcome data can affect an estimate when the chance of a measurement being absent is related to participant characteristics or outcomes. The direction and size of any effect depend on the pattern of missingness and the analysis assumptions. No pattern or handling method can be inferred.

The record does not provide the statistical analysis plan, any interim-analysis details, or a sample-size justification. Those elements are not reported in the registry record. The planning assumptions mentioned for an illustration do not establish the trial's original analysis strategy. These reporting gaps limit assessment of how the endpoint result would have been selected, analyzed, and interpreted, especially if several analyses were conducted.

11. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diabetic metabolic decompensation (0.6%), foetal death (0.6%).

The registry lists one serious adverse event in the BE-PEP group, with 157 at risk, and one in the SDR-PEP group, with 156 at risk. It lists 65 participants affected by other adverse events in BE-PEP, with 157 at risk, and 50 in SDR-PEP, with 156 at risk. No deaths are listed in either group. These figures are registry-reported counts and should be read separately by outcome category.

The record names diabetic metabolic decompensation and foetal death among the top serious-event terms, with each listed as 0.6%. It does not report which arm each term occurred in, so those terms should not be assigned to a group. The registry record does not provide event-level descriptions, timing, duration, or a statistical comparison of the adverse-event counts. It also does not explain whether the other adverse-event counts represent people with at least one event or how repeated events were counted.

In general, adverse-event counts describe what was recorded under the study's definitions; they do not alone establish causation. Differences in counts are descriptive and do not show whether any difference is statistically precise. The absence of listed deaths in these groups is a registry observation, not evidence about risks outside the recorded study population or follow-up.

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

The posted record describes a randomized, open-label, parallel phase 2 study comparing bedaquiline plus rifampicin with single-dose rifampicin as post-exposure prophylaxis for leprosy. Its stated primary question concerns the mean QTc interval difference 24 hours after treatment administration, among participants included per protocol. This identifies the safety measure and comparison but does not supply the numerical primary result.

The registry record does not report the mean difference or its 95% confidence interval. As a result, the result's direction, size, and precision cannot be assessed. The recorded status of completed does not fill this gap. The adverse-event counts offer descriptive safety information, but the record does not include the detail needed to make a formal comparative assessment of those events.

The study's phase 2 safety context is important. The record says the safety study precedes a main study, and its brief summary describes a broader program of bedaquiline-enhanced post-exposure prophylaxis. The phase 2 endpoint is not a reported measure of whether prophylaxis prevents leprosy. The registry record therefore does not establish an effect on leprosy incidence, nor does the primary QTc endpoint establish overall safety across longer follow-up.

In general, a randomized comparison can provide evidence about differences between assigned groups when the trial conduct, outcome measurement, and analysis are sufficiently documented. Here, important details—including the endpoint estimate, analysis population size, missing-data handling, and analysis plan—are not reported in the registry record. These limits mean that the posted information supports a description of the design and recorded adverse-event counts, but not a conclusion about the comparative effect of the regimens.

13. Why This Trial Matters Statistically

This trial is statistically notable for framing a phase 2 safety question as a randomized comparison of two prophylaxis regimens. The primary endpoint is a continuous measure, QTc interval, and the estimand is explicitly expressed as a mean difference between arms. This makes the intended contrast clear: BE-PEP minus SDR-PEP at 24 hours after treatment administration.

Precision is central to interpreting a safety comparison. A point estimate alone would describe the observed difference, while its confidence interval would show the uncertainty around that estimate. The registry specifies a 95% confidence interval but does not report its limits or the mean difference. As a result, the available record cannot show whether the comparison was precise or compatible with a range of materially different values.

There is also a useful distinction between the trial's stated purpose and what the primary outcome can answer. The record describes a safety study preceding a main study, while the primary endpoint concerns a short-term QTc measure. It is not a reported clinical efficacy endpoint for leprosy prevention. Keeping the endpoint aligned with the study question avoids interpreting a safety measurement as evidence about prevention outcomes.

The registry also lists adverse-event counts by treatment arm. These can orient readers to the posted safety record, but without event definitions, analysis details, and uncertainty estimates, counts alone do not establish a comparative difference. The per-protocol primary population and the lack of reported missing-data and multiplicity details further limit assessment. Statistically, the most important feature of the registry record is therefore the contrast it defines alongside the substantial absence of the numerical primary result.

14. 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 numerical primary endpoint result is not reported in the registry record. Neither the mean difference in QTc interval nor its 95% confidence interval is available, so the principal safety comparison cannot be interpreted for direction, magnitude, or precision. The record identifies participants included per protocol but does not report how many contributed to the endpoint or the criteria for inclusion in that population.

The record does not describe the method of random-sequence generation, allocation concealment, outcome measurement procedures, or the handling of missing measurements. Masking is listed as none. The registry record also does not report the statistical analysis plan, details of covariate adjustment, sensitivity analyses, interim analyses, or multiplicity procedures. These omissions prevent a detailed appraisal of whether the analysis followed a prespecified strategy.

The treatment descriptions differ in scope: the arm description specifies one dose of bedaquiline plus rifampicin, while the brief summary discusses weight-dependent bedaquiline dosing and a repeat dose after four weeks for household contacts as part of the intended broader regimen. The record does not fully reconcile these descriptions for the phase 2 safety study. The exact timing and extent of follow-up beyond the primary 24-hour assessment are not reported in the registry record.

Adverse-event reporting is limited to counts, at-risk counts, and selected serious-event terms. The record does not give event-level detail, arm attribution for the named terms, exposure time, or statistical comparisons. It does not explain how repeated events were handled. These limitations mean that the posted adverse-event summaries should not be treated as a complete comparative safety analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy (Phase 2) — NCT05406479.
• Registry record last updated 2024-08-28; status last verified 2024-08.
• Results first posted 2024-08-28.
• 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.

18. Record Summary

The registry identifies NCT05406479 as a completed phase 2 randomized, open-label, parallel study sponsored by the Institute of Tropical Medicine, Belgium. Recorded enrollment is 313; the start date is 2022-07-14 and the primary completion date is 2023-01-26. The study concerns bedaquiline-enhanced post-exposure prophylaxis for leprosy in Comoros.

The two arms are BE-PEP, bedaquiline plus rifampicin, and SDR-PEP, single-dose rifampicin. The primary endpoint is the mean difference in QTc interval 24 hours after treatment administration, defined as BE-PEP minus SDR-PEP, among participants included per protocol. Its estimate and 95% confidence interval are not reported in the registry record.

The record reports serious and other adverse-event counts by arm and no deaths in either group. It does not report the analysis plan, endpoint analysis population size, missing-data handling, or multiplicity procedures. The posted information describes the study design and selected safety counts but does not provide the numerical primary comparison.