A Clinical Trial of the Safety, Pharmacokinetics and Hematologic Effects of Imatinib on Myelopoiesis in Adults When Given With and Without Isoniazid and Rifabutin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Trial of the Safety, Pharmacokinetics and Hematologic Effects of Imatinib on Myelopoiesis in Adults When Given With and Without Isoniazid and Rifabutin (NCT03891901), a non-randomized phase 2 study. The primary outcome is Number of Myelomonocytic Cells in the Blood.

2. Clinical Question

3. Trial Design

NCT03891901, titled IMPACT-TB, is a completed Phase 2 clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The registry records a start date of 2020-10-27 and a primary completion date of 2022-08-30. Enrollment was 24. The study concerned adults with tuberculosis and assessed imatinib’s safety, pharmacokinetics, and effects on myelopoiesis when given with and without isoniazid and rifabutin.

The design was non-randomized, unmasked, and sequential. The listed Cohort 1 groups used imatinib doses of 50 mg, 100 mg, 200 mg, or 400 mg. Participants in those groups received imatinib for 14 days, followed by 14 days of imatinib together with rifabutin and isoniazid. Cohorts 2a and 2b began with 14 days of isoniazid and rifabutin, followed by 14 days of all three drugs; the imatinib dose was to be determined after analysis of Cohort 1 data. Other listed groups received imatinib at 100 mg, 200 mg, or 400 mg daily for 28 days. The registry’s adverse-event groups include some, but not all, of these listed regimens.

Sequential dose evaluation is not equivalent to a randomized dose comparison. The record does not describe a randomized allocation process, masking, or a concurrent control group. Cohort and regimen differences therefore matter when interpreting changes across treatment periods or groups. The registry does not report the protocol’s stopping rules, dose-escalation criteria, or the method used to select the Cohort 2 dose. The stated aim was to establish a dose for study in a subsequent Phase IIB trial of imatinib as an adjunct to an antimicrobial regimen.

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.

Before assignment: A total of 42 individuals were screened and 18 did not meet eligibility criteria or withdrew prior to the baseline assessment, resulting in 24 study participants initiating study activities.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population includes participants who completed the 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 Myelomonocytic Cells in the Blood, measured over Days 1, 7, 14, 21, 28, 42.

The primary endpoint was the number of myelomonocytic cells in blood, expressed in cells per microliter (µL). Counts were scheduled for Days 1, 7, 14, 21, 28, and 42. The registry describes the analysis as a mean with standard deviation and says the analysis population includes participants who completed the study.

These cell counts were used to assess immunologic effects of study treatment. The stated rationale was that an increase in myelomonocytic cells would help determine an appropriate therapeutic dose of imatinib. This makes the endpoint a biological measure relevant to dose selection, rather than a direct measure of tuberculosis treatment success. The registry does not report numerical cell counts, mean changes, standard deviations, or estimates comparing dose groups. It also does not report how the repeated measurements were combined into a primary summary or how missing measurements were handled. Without those details and the outcome values, the direction and precision of the observed changes cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a continuous primary outcome: a mean number of myelomonocytic cells, with standard deviation as the measure of dispersion. General statistical explanation: a mean summarizes the central level of a quantitative measure, while a standard deviation describes how much individual observations vary around that mean. Neither quantity alone shows how precisely a group mean has been estimated. Precision depends on the amount of available data and its variability, among other factors. The registry does not post the primary outcome means or standard deviations, so readers cannot assess these features from the record.

What does a confidence interval communicate?

General statistical explanation: a confidence interval gives a range of values compatible with a statistical estimate under the model and procedures used to construct it. A narrower interval indicates greater statistical precision than a wider interval, but it does not remove bias from a non-randomized design or establish that a comparison is causal. The registry record does not report confidence intervals for the primary endpoint or the listed pharmacokinetic outcomes. As a result, the precision of those estimates is not available for interpretation.

Why does the design affect comparisons?

General statistical explanation: random allocation can help balance known and unknown participant characteristics across treatment groups, on average. In a non-randomized study, treatment groups may differ for reasons other than the assigned regimen. A sequential design can also make dose, cohort, and timing closely linked. If cell counts differ between groups or periods, the difference cannot automatically be attributed to imatinib dose or co-treatment. The record identifies non-randomized allocation, no masking, and a sequential model, but it does not report an adjusted comparative analysis or a statistical method for separating these influences.

The sequence described for Cohort 1 includes an imatinib-only period followed by a period adding rifabutin and isoniazid. The Cohort 2 descriptions reverse the initial regimen: participants begin with isoniazid and rifabutin and then add imatinib. These sequences may allow observation of measurements over time under changing regimens, but the registry does not describe a formal model for repeated measurements, period effects, or carryover. It is therefore not possible to infer how such issues were handled analytically.

How should the planning illustrations be read?

General statistical explanation: planning calculations translate a chosen effect size and statistical assumptions into a target sample size. The record describes illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the target effect is a stated fraction of the observed effect. These are planning assumptions, not a record of the trial’s actual design justification. The illustrations do not represent observed power. For continuous outcomes, the planning output is expressed as participants per arm; the registry’s general description distinguishes this from time-to-event calculations, which use a total number of events.

Because the registry does not report the observed primary endpoint effect, it is not possible to assess the numerical basis of those planning illustrations from the record. They should not be interpreted as showing that a particular number of participants was enrolled for a prospectively justified target, or that the trial had a particular probability of detecting an effect. Sample-size planning and estimation precision are related, but a post hoc illustration does not establish the quality of the original design.

The record lists 16 outcome measures and zero analyses. The listed secondary measures include white blood cell count and pharmacokinetic measures for imatinib and isoniazid. No statistical model, transformation, covariate adjustment, missing-data procedure, or method for analyzing these secondary outcomes is reported in the registry record. General statistical explanation: analysis choices can affect estimates and uncertainty, particularly when measurements are repeated or distributions are skewed. Pharmacokinetic measures such as area under the curve or maximum concentration may require methods suited to their distributions, but the registry does not specify what methods were used.

Standard deviation and standard error are not interchangeable. General statistical explanation: standard deviation describes variation among observations, while standard error describes uncertainty in an estimated mean. A mean and standard deviation can help characterize the data, but do not by themselves give an interval for a treatment contrast. Since the registry reports neither outcome summaries nor comparative estimates, no recalculated comparison can be made from the posted record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures, including the primary blood-cell endpoint and several secondary measures. It does not report a multiplicity-adjustment method, a hierarchy for testing outcomes, or a plan for choosing among multiple time points. Without that information, the degree to which the analysis controlled the chance of false-positive findings across multiple tests is not reported in the registry record. The absence of posted analyses also means there are no outcome-specific results or inferential procedures to evaluate.

The primary analysis population is described as participants who completed the study. However, the number of completers is not reported in the registry record, nor are the numbers with available observations at each scheduled day. The record does not describe exclusions, withdrawals, imputation, or other missing-data procedures. It also does not say whether all enrolled participants were included in safety summaries or how participants were assigned to the displayed adverse-event groups.

General statistical explanation: restricting an analysis to participants who completed a study can produce a different estimate from an analysis that includes all participants, especially if completion is related to health status, treatment exposure, or outcome values. Repeated measurements can also be incomplete: some participants may contribute data at some visits but not others. How those patterns are handled can affect both the estimated mean trajectory and its uncertainty. No specific approach can be attributed to this trial from the registry record.

The registry does not report a prespecified statistical analysis plan, details of interim analyses, or rules governing stopping or dose selection. These items are not reported in the registry record. Their absence from the record should not be taken as proof that no procedures existed outside the registry; it means they cannot be assessed from the registered information.

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 non-serious adverse event terms

The registry reports serious adverse events for five displayed groups. In each group, the number at risk and the number affected by serious adverse events are recorded; the affected count is 0 for every listed group. The listed numbers at risk are 16, 14, 6, 3, and 2, respectively, corresponding to the displayed groups. No deaths are recorded for these groups. The registry lists no top serious-event terms.

Other adverse events are recorded separately. The numbers affected are 16 of 16 in the Cohort 1a imatinib 50 mg group; 12 of 14 in the Cohort 1a combination group; 5 of 6 in the Cohort 1b imatinib 100 mg group; 3 of 3 in the Cohort 1b combination group; and 2 of 2 in the imatinib 100 mg group. These are participant counts in the categories reported, not a count of all individual event episodes.

These descriptive safety figures apply to the groups shown in the registry. Group sizes differ, and the trial was non-randomized, so the counts do not support a like-for-like comparison of risk between regimens. Zero recorded serious events in these groups does not establish that serious events are impossible or that the regimens have equivalent safety. The registry does not report event details or exposure-adjusted rates.

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

The registry record establishes that IMPACT-TB was a completed Phase 2 study designed to evaluate imatinib’s safety, pharmacokinetics, and effects on myelopoiesis in adults with tuberculosis, with and without isoniazid and rifabutin. It specifies a blood-cell endpoint, six scheduled measurement days, several treatment sequences, and the intention of using the findings to select an imatinib dose for a subsequent Phase IIB study.

It does not establish what changes in myelomonocytic cell counts occurred. The numerical primary endpoint results, their variability, and estimates of precision are not reported in the registry record. Nor are numerical results reported for the listed pharmacokinetic outcomes. Without these findings, the record cannot show the magnitude or consistency of any biological response or how it varied by dose and regimen.

The record also does not establish a causal effect of imatinib, because allocation was non-randomized and the design was sequential. Any unreported or future comparisons across cohorts would need to account for differences in regimen, sequence, and participant composition; the registry does not report an adjusted analysis that addresses these issues. The study’s dose-selection purpose should not be confused with a demonstration of clinical benefit in tuberculosis.

The posted safety counts describe the listed groups and categories only. Zero serious adverse events are recorded among those groups, alongside other adverse events affecting participants. These figures are not a randomized comparison, and the registry does not provide detailed event terms or rates adjusted for exposure. The record therefore supports a descriptive account of what was registered, but not a broad conclusion about relative safety or treatment efficacy.

13. Why This Trial Matters Statistically

This trial is statistically notable for linking dose selection to a biological endpoint while using a sequential, non-randomized design. That design can be useful for gathering early safety, pharmacokinetic, and biologic information, but it does not have the same interpretation as a randomized comparison. Separating dose effects from regimen and time effects is important when considering results from sequential treatment periods.

The primary measure was collected at multiple scheduled days, making the analysis of change over time central to interpretation. A reader would ordinarily want to know how repeated observations were summarized, how incomplete measurements were handled, and how uncertainty around changes was quantified. Those details and the numerical outcome estimates are not reported in the registry record. The record therefore describes an intended measurement strategy without enabling assessment of the observed trajectory.

The study’s stated role was to inform a subsequent Phase IIB dose choice, rather than to provide a definitive clinical outcome comparison. That distinction matters: a dose-selection study can address biological and pharmacological questions without establishing whether an adjunctive regimen improves tuberculosis outcomes. The registry’s safety counts are also descriptive, with varying group sizes and no randomized comparison.

Finally, the registry lists many outcome measures but no posted analyses. This limits the ability to evaluate multiplicity, precision, and consistency across outcomes. The sample-size illustrations are planning aids based on an observed effect and stated assumptions; they are not evidence of observed power or of the original design rationale. Taken together, the registered design and endpoints explain the trial’s statistical aims, while the lack of posted results limits what can be concluded about its findings.

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.

Several limitations specific to this record constrain statistical interpretation. The primary outcome is described, but its mean values, standard deviations, and comparative estimates are not reported in the registry record. The record also lists zero analyses, so there are no posted estimates or inferential results for the primary or secondary outcomes. The enrollment of 24 does not indicate how many participants completed the study or contributed measurements at each scheduled time.

The non-randomized, sequential design does not provide a like-for-like control comparison. Regimens and treatment order differ across the listed cohorts, and Cohort 2 imatinib doses were to be determined after analyzing Cohort 1 data. The registry does not describe the dose-selection rules, stopping criteria, or a method for accounting for sequence and time effects. These details are not reported in the registry record.

The statistical analysis plan, including any repeated-measures approach, covariate adjustment, multiplicity procedure, or missing-data method, is not reported in the registry record. The record also does not give participant flow by cohort or explain the relationship between all listed intervention groups and the five adverse-event groups. Safety counts are therefore limited to the displayed groups and categories.

The planning illustrations use the observed effect under stated assumptions, but the observed primary endpoint effect is not reported in the registry record. Those calculations cannot fill the gap in outcome reporting or establish the trial’s original sample-size justification. Together, these limitations mean that the registered design can be described, but the magnitude, precision, and robustness of the trial’s findings cannot be evaluated from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Clinical Trial of the Safety, Pharmacokinetics and Hematologic Effects of Imatinib on Myelopoiesis in Adults When Given With and Without Isoniazid and Rifabutin — NCT03891901.
• Registry record last updated 2023-10-23; status last verified 2023-08.
• Results first posted 2023-09-28.
• 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

NCT03891901, IMPACT-TB, was a completed Phase 2, non-randomized, unmasked, sequential study sponsored by NIAID, with enrollment of 24. It evaluated imatinib in adults with tuberculosis, including regimens with rifabutin and isoniazid. The primary endpoint was the mean number of myelomonocytic cells in blood at Days 1, 7, 14, 21, 28, and 42; the stated analysis population was participants who completed the study.

The registry lists 16 outcome measures and zero analyses. Numerical primary and pharmacokinetic results, completion counts, missing-data methods, and the statistical analysis plan are not reported in the registry record. Five adverse-event groups are displayed, with 0 serious adverse events recorded in each and no deaths recorded. Other adverse events affected participants in each listed group. The trial’s stated purpose was to inform an imatinib dose for a subsequent Phase IIB study.