Prophylaxis of Visceral Leishmaniasis Relapses in HIV Co-infected Patients With Pentamidine: a Cohort Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prophylaxis of Visceral Leishmaniasis Relapses in HIV Co-infected Patients With Pentamidine: a Cohort Study (NCT01360762), a na phase 3 study. The primary outcome is Probability of Relapse-free Survival.

2. Clinical Question

The clinical question is about outcomes during secondary prevention after treatment for visceral leishmaniosis, rather than about initial treatment of an episode. The record describes participants with HIV co-infection, a group for whom relapse prevention is the stated purpose of the intervention. It identifies pentamidine as the prophylactic agent and relapse-free survival as the primary endpoint.

Because the study has one group and no randomized comparator, its primary question is descriptive: what outcomes were recorded among participants receiving the prophylaxis strategy? It cannot directly estimate how outcomes would have differed under another treatment or no prophylaxis. The registry does not report the observed month 6 or month 12 relapse-free survival probabilities or their confidence intervals. It also does not give a fuller operational definition of relapse for the endpoint. Those omissions limit how specifically the clinical question can be answered from the registry record.

3. Trial Design

The record describes a prospective cohort study of secondary prophylaxis for visceral leishmaniosis in people with HIV. It is registered as phase 3 and lists 74 participants as the enrollment. The recorded study status is completed. The start is listed as 2011-11 and primary completion as 2015-11. The sponsor is the Institute of Tropical Medicine, Belgium.

The study is a single-group design. Its sole intervention group is named Pentamidine Secondary Prophylaxis (PSP); allocation is listed as not applicable, and masking is listed as none. The arm description says that participants with HIV and visceral leishmaniosis, after treatment for visceral leishmaniosis, receive pentamidine to prevent relapses. The described treatment period is 12 months, plus an extended period of 0 to 6 months whose details are truncated in the registry record.

This design can document outcomes and adverse events among participants receiving the prophylaxis strategy. It does not provide a concurrent control group, and there is no randomized comparison. Consequently, the record cannot by itself separate outcomes associated with prophylaxis from outcomes that might have occurred because of the underlying condition, prior treatment, or other aspects of care. These are design limits on interpretation, not evidence that the intervention did or did not affect outcomes.

The registry lists three secondary outcome categories: participants with adverse events, treatment discontinuations and interruptions, and required additional interventions. It lists five outcome measures overall, but does not provide enough detail in the record to reconstruct all measurement definitions. A detailed protocol, eligibility criteria, recruitment procedures, and the rationale for the planned enrollment 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.

Main Study Period (12-month Treatment)

Reasons for not completing this period:

Whole Study Period

Reasons for not completing this period:

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 Probability of Relapse-free Survival, measured over up to 1 year after the start of the intervention (PSP).

The primary endpoint is titled probability of relapse-free survival. It is expressed as a percentage probability and is specified for up to one year after the start of the intervention, with assessment at month 6 and month 12. The registry says that the endpoint is accompanied by a 95% confidence interval. No observed probability or confidence interval is reported in the registry record.

In general, a relapse-free survival endpoint describes the probability of remaining without the event of interest over a period of follow-up. It is useful when timing matters, because it can describe outcomes at specified follow-up points rather than only counting whether an event occurred at any time. A confidence interval communicates the statistical uncertainty around an estimate; it does not ensure that the estimate is free from bias or that the study design supports a causal conclusion.

The registry does not report the operational definition of relapse, how deaths were handled in the endpoint, or how participants lost to follow-up were treated. It also does not provide the method used to estimate the month 6 and month 12 probabilities. These details matter for interpretation: different event definitions, censoring rules, and estimation methods can change what an endpoint estimate represents. The endpoint name and scheduled time points alone do not resolve those questions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group cohort estimate?

This study is recorded as a single-group prospective cohort, with pentamidine secondary prophylaxis as the intervention. In general, a cohort study follows participants who share a defined exposure or treatment strategy and describes outcomes during follow-up. A single-group design can document what happened in that group. Without a concurrent comparator, it does not directly estimate the contrast between the observed treatment strategy and an alternative strategy.

The registry lists allocation as not applicable and masking as none. These entries are consistent with the absence of a randomized, masked comparison, but the record does not describe additional procedures for outcome assessment. An observed outcome in a cohort can reflect several influences, including the underlying condition and other care. For that reason, a descriptive outcome should not automatically be read as an effect caused by the intervention.

How should relapse-free survival be understood?

In general, survival analysis is used when both whether an event occurs and when it occurs are relevant. A relapse-free survival probability at a specified time summarizes the estimated chance of remaining free of the defined event up to that time. The registry specifies month 6 and month 12 assessments and a 95% confidence interval, but does not report the estimates or the method used to obtain them.

The interpretation depends on the endpoint rules. The record does not define relapse in operational terms, specify whether death is part of the event definition, or describe censoring. Censoring is a statistical way to account for a participant whose event status is not observed through the full follow-up period. In general, the validity of a survival estimate depends on how incomplete follow-up is handled and on assumptions about why follow-up ends. The registry record does not give the details needed to assess those assumptions.

A confidence interval, in general, represents uncertainty around an estimated quantity under the statistical method used. It is not a guarantee that the true value lies within the particular interval, and it does not account automatically for design limitations, measurement problems, or bias. Since no interval is reported for the primary endpoint, its precision cannot be assessed from the registry record.

What can safety counts tell readers?

In general, an adverse-event count describes events or affected participants according to the registry’s reporting convention. The PSP group has 74 listed as at risk for serious adverse events and 33 listed as affected; for other adverse events, 74 are listed as at risk and 71 as affected. The registry also lists 7 deaths. These are descriptive counts. They do not establish that the intervention caused an event, and the single-group design offers no randomized safety comparison.

The record lists percentages beside several serious-event terms but does not specify their denominators or whether the percentages refer to participants, events, or another reporting unit. A percentage without its denominator and counting rules can be difficult to translate into a participant-level risk. The safest interpretation is to report each term with its listed percentage and not infer a different measure.

What statistical plan is documented?

The registry record lists zero analyses. It does not report a detailed statistical analysis plan, a sample-size justification, an interim analysis plan, or a method for handling missing data. The planned enrollment of 74 should therefore not be treated as evidence that the study was designed to achieve a particular precision or power for the primary endpoint. It is also not possible to reconstruct an analysis plan from the endpoint title and follow-up times alone.

In general, statistical methods should be chosen to match the endpoint, follow-up structure, and analysis population. For time-to-event outcomes, methods need to define the event, specify how censoring is handled, and state which participants contribute to each estimate. Reporting participant flow and uncertainty alongside the estimates helps readers understand how much data support the results. Those details are not reported in the registry record, and no new estimates can be derived from the posted summary information.

The record includes planning assumptions for illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions, not a description of this trial’s single-group design or its own statistical plan. Such illustrations are not observed power and do not establish that the cohort could answer a comparative question. Since no effect estimate for the primary endpoint is reported, the illustrations should not be mistaken for results from this cohort.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan or any analyses. It therefore does not say how the primary endpoint and secondary outcomes were prioritized in statistical testing, whether any adjustment for multiple testing was planned, or whether specific comparisons were prespecified. The primary endpoint is identified by title, but the record does not report a test result or an estimate that could be interpreted in light of multiplicity.

In general, examining several outcomes or time points can increase the chance of finding an apparently notable result by chance if each is tested separately. Multiplicity procedures can address that issue, but their use depends on the planned estimands and analysis strategy. Here, the specified primary outcome has assessments at month 6 and month 12, and three secondary outcome categories are listed. The registry record does not explain whether those outcomes were to be analyzed together, treated as separate descriptive summaries, or tested under a formal hierarchy.

Missing-data handling is also not reported. The record does not give the number of participants with complete follow-up at either primary endpoint time point, reasons for missing observations, or any imputation or censoring approach. The analysis population is not defined, and the record does not state whether all enrolled participants were included in each outcome summary. Enrollment of 74 should not be assumed to equal the analysis population for every outcome.

These omissions do not show that analyses were not conducted; they mean the registry record does not document them. Without the analysis population, missing-data rules, and multiplicity approach, readers cannot fully assess the robustness or precision of any primary or secondary result. In this case, the primary endpoint results themselves are not reported in the registry record.

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: visceral leishmaniasis (27.0%), pneumonia (21.6%), renal failure (2.7%), hypovolemic shock (2.7%), diarrhoea (1.4%).

For the Pentamidine Secondary Prophylaxis group, the registry lists 74 participants at risk for serious adverse events and 33 affected. For other adverse events, it lists 74 at risk and 71 affected. The record also lists 7 deaths. These are reported safety counts; the registry does not provide enough detail to determine event timing, severity grading beyond the serious-event classification, or causal attribution.

The serious-event terms are listed with these percentages: visceral leishmaniasis, 27.0%; pneumonia, 21.6%; renal failure, 2.7%; hypovolemic shock, 2.7%; diarrhoea, 1.4%; and upper gastro-intestinal haemorrhage, 1.4%. The denominator and counting convention for the percentages are not reported in the registry record. They should not be reinterpreted as risks among participants or as percentages of all events without that information.

These summaries do not establish that pentamidine caused the events. In general, safety findings in a single-group cohort are descriptive: they record events during observation but lack a randomized comparator for separating treatment-related events from events associated with the illness or other circumstances. The record does not report a comparative safety analysis.

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

The record documents a prospective cohort study of pentamidine secondary prophylaxis in people with HIV and visceral leishmaniosis following treatment for visceral leishmaniosis. Its primary outcome was probability of relapse-free survival through one year, with assessments at month 6 and month 12. It also records safety summaries for the intervention group, including counts of participants affected by serious and other adverse events and a death count.

What the record does not establish is the magnitude or precision of the primary outcome. The month 6 and month 12 estimates and their 95% confidence intervals are not reported in the registry record. Thus, readers cannot quantify the recorded relapse-free survival from this information. The record also does not report enough endpoint and analysis details to determine how relapse, death, or incomplete follow-up were handled.

The cohort design has no concurrent control group and no randomized comparison. Even if an outcome estimate were available, it would describe participants in the prophylaxis group and would not, by itself, show what would have happened under another strategy. The enrollment count and safety counts cannot establish a treatment effect, and they should not be treated as comparative evidence.

Similarly, the presence of adverse events or deaths during the study does not establish that pentamidine caused them. The posted safety information is descriptive, and the record does not report causal assessments or comparative rates. The serious-event percentages also lack a stated denominator and counting convention. The most defensible conclusion is therefore limited: the registry describes the intervention, cohort, planned primary endpoint, and some safety counts, but it does not report the primary outcome results needed to characterize relapse-free survival or its uncertainty.

13. Why This Trial Matters Statistically

This study addresses a statistical question that is inherently about follow-up over time: whether participants remain free of relapse after secondary prophylaxis begins. Specifying month 6 and month 12 gives the primary endpoint a time-based structure, rather than reducing follow-up to a simple count at an unspecified time. In general, this makes the event definition, follow-up completeness, and handling of censoring central to interpretation.

The record also illustrates why design and endpoint reporting need to be read together. A single-group cohort can provide useful descriptive information about outcomes and safety in the group receiving a strategy. It cannot provide a randomized estimate of how that group’s outcomes compare with an alternative. The distinction matters especially when a study’s clinical motivation is prevention: a prevention question may invite a comparative interpretation, but the recorded design is not comparative.

Safety summaries raise a related reporting issue. Counts, affected-participant totals, and event-term percentages are not interchangeable measures. The denominator and counting convention determine what a percentage means. Since those details are not reported for the listed serious-event percentages, restraint in interpretation is necessary.

Finally, this record shows the difference between having a clearly named primary endpoint and having a reportable estimate for that endpoint. The outcome is named, and the intended assessment times and confidence-interval type are given. Yet the actual probabilities and intervals are absent. Without them, neither the observed level of relapse-free survival nor its statistical precision can be evaluated from the registry record. Complete outcome reporting is essential for turning a registered question into interpretable evidence.

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 main trial-specific limitation is the single-group design. There is no concurrent control group, and allocation is listed as not applicable. Outcomes among participants receiving pentamidine can therefore be described, but the registry record does not support a direct comparison with another strategy.

The primary endpoint results are not reported. Although relapse-free survival is specified at month 6 and month 12 with a 95% confidence interval, the actual probabilities and intervals are absent. The record also does not give an operational relapse definition, death-handling rule, or censoring method. These gaps prevent a detailed assessment of what the endpoint captures and how it was estimated.

Enrollment is listed as 74, but the record does not report analysis populations or participant flow for the primary outcome. The number with complete follow-up, reasons for missing observations, and approach to missing data are not reported in the registry record. As a result, enrollment should not be taken to represent the number contributing to each outcome estimate.

The safety summaries have their own interpretive limits. The record gives counts for participants at risk and affected, plus 7 deaths, but does not report timing or causal attribution. The denominator and counting convention for the serious-event percentages are not stated. A concurrent comparison and fuller event reporting would be needed to interpret relative safety; neither is documented.

Finally, the statistical analysis plan, sample-size justification, and any interim-analysis plan are not reported in the registry record. The record’s completed status does not fill these gaps or substitute for primary outcome results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Prophylaxis of Visceral Leishmaniasis Relapses in HIV Co-infected Patients With Pentamidine: a Cohort Study — NCT01360762.
• Registry record last updated 2019-02-15; status last verified 2018-10.
• Results first posted 2019-02-15.
• 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

This completed, phase 3 prospective cohort study records enrollment of 74 participants with HIV and visceral leishmaniosis who had been treated for visceral leishmaniosis. The single intervention group received pentamidine secondary prophylaxis, described as a 12-month treatment period plus an extended period of 0 to 6 months. The study has no randomized comparator and is listed as unmasked.

The primary endpoint is probability of relapse-free survival up to one year after the intervention starts, assessed at month 6 and month 12 with a 95% confidence interval. The endpoint estimates and intervals are not reported in the registry record. The safety record lists 33 of 74 at risk as affected by serious adverse events, 71 of 74 at risk as affected by other adverse events, and 7 deaths; listed serious-event percentages do not have a stated denominator or counting convention. The record does not report the statistical analysis plan, analysis populations, or missing-data methods.