This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia (NCT01960413), a randomized phase 2 study. The primary outcome is Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01960413 |
| Phase | Phase 2 |
| Condition | Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 46 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Vanderbilt University Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The registry record identifies people with sickle cell anemia, specifically HbSS or HbSβ-thalassemia0. It describes the study as a feasibility trial. The record does not report further eligibility details in the primary outcome description, so the clinical question should be understood within this stated population rather than generalized to other groups.
Intervention
The intervention was oral montelukast taken daily for eight weeks alongside participants’ current hydroxyurea regimen. The comparison concerns adding montelukast to ongoing hydroxyurea, not replacing hydroxyurea with montelukast.
Comparator
The comparator was oral placebo taken daily for eight weeks alongside the current hydroxyurea regimen. The randomized comparison therefore contrasts montelukast with placebo as an addition to hydroxyurea.
Primary question
The primary outcome was change in soluble vascular cell adhesion molecule-1, or sVCAM, from baseline to eight weeks, measured in ng/mL and summarized using the median and inter-quartile range. The central statistical question is whether the posted changes distinguish the montelukast-addition group from the placebo-addition group, and how precisely the registry record estimates that contrast. The record gives outcome values for both groups but does not report a formal between-group analysis or a p-value. The posted values therefore describe the groups’ outcomes; by themselves, they do not establish the size or uncertainty of a treatment contrast.
3. Trial Design
NCT01960413 is a completed phase 2 study sponsored by Vanderbilt University Medical Center. The registry record describes randomized allocation, triple masking, and a parallel-group model. Participants were assigned to receive either montelukast added to hydroxyurea or placebo added to hydroxyurea. Both study treatments were taken orally each day for eight weeks, while participants continued their current hydroxyurea regimen. The stated comparison is therefore the additional effect associated with montelukast versus placebo in the context of hydroxyurea treatment.
The registry lists enrollment as 46. The primary outcome listing gives group n values of 20.0 for montelukast added to hydroxyurea and 21.0 for placebo added to hydroxyurea. These are separate registry entries; they should not be combined to infer the number included in an analysis, because the analysis population and handling of participants without outcome data are not reported in the registry record. The study’s stated purpose was feasibility, and its description says the investigators would compare the two groups over a total of eight weeks.
The record lists a start date of 2013-11, primary completion of 2018-03, and status as completed. It does not report details of the randomization sequence, allocation concealment, masking procedures, adherence, or protocol deviations. The labels randomized, triple masking, and parallel describe important features of the design, but they do not supply those operational details. The registry record also does not report a statistical analysis plan or explain how any additional study aims were analyzed. The primary outcome is the only posted outcome measure described in the available record, and the record lists no analyses for it.
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
| Stage | Montelukast Added to Hydroxyurea | Placebo Added to Hydroxyurea |
|---|---|---|
| STARTED | 24 | 22 |
| COMPLETED | 20 | 21 |
| NOT COMPLETED | 4 | 1 |
Reasons for not completing this period:
| Reason | Montelukast Added to Hydroxyurea | Placebo Added to Hydroxyurea |
|---|---|---|
| Withdrawal by Subject | 1 | 1 |
| Physician Decision | 1 | 0 |
| Lost to Follow-up | 2 | 0 |
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.
| Characteristic | Unit | Montelukast Added to Hydroxyurea | Placebo Added to Hydroxyurea | Total |
|---|---|---|---|---|
| Participants analysed | 24 | 22 | 46 | |
| Age, Continuous | years | 29.25 (SD 10.46) | 30.76 (SD 10.24) | 29.95 (SD 10.27) |
| Sex: Female, Male: Female | Participants | 13 | 14 | 27 |
| Sex: Female, Male: Male | Participants | 11 | 8 | 19 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 23 | 22 | 45 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 24 | 18 | 42 |
| Race (NIH/OMB): White | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 | 3 | 3 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 24 | 22 | 46 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM), measured over baseline to eight weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in soluble vascular cell adhesion molecule-1, abbreviated sVCAM, from baseline to eight weeks. The stated unit is ng/mL, and the registry identifies the summary statistic as the median with inter-quartile range. sVCAM is the biomarker named by the trial record; the record’s stated rationale treats its reduction as a measure of interest in this feasibility study. The endpoint is not a direct count of clinical events or a patient-reported symptom measure.
The registry description frames the study around detecting a 30% reduction in sVCAM, described as approximately 106 ng/ml. It also states that the planned group size was intended to explore all three aims and potential confounders, and describes a smaller accrual scenario in which the investigators would still be able to detect a 30% difference. These are design considerations recorded by the investigators, not findings from the posted outcome. The record’s description of a clinically relevant reduction is the investigators’ stated rationale; it does not establish that a reduction occurred in the posted results.
Because the endpoint is reported with medians and inter-quartile ranges, interpretation should focus on the distributional summaries as recorded, rather than assuming that the data are normally distributed or that the median is a mean. A biomarker change can help characterize a biological outcome, but the registry record does not report how it relates to clinical outcomes in this trial.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry outcome listing reports a value of -3.2 for the montelukast-added-to-hydroxyurea group and 4.17 for the placebo-added-to-hydroxyurea group. The endpoint is change in sVCAM from baseline to eight weeks, with units of ng/mL. The record identifies the summary as a median and the dispersion as an inter-quartile range. It also lists bounds of -13.6 to 11.6 for the montelukast group and -3.3 to 12.1 for the placebo group. The registry does not clarify in the outcome description what those bounds represent, so they should not be assigned a more specific interpretation from the record alone.
The posted values are group summaries, not a reported estimate of the between-group treatment effect. The registry lists no analyses for the primary outcome and gives no p-value, adjusted estimate, or confidence interval for the randomized comparison. Consequently, the group values alone do not establish whether the observed difference between groups is compatible with chance variation, nor how precisely a treatment contrast is estimated. The absence of a reported analysis is not evidence that no analysis was performed; it means the analysis is not reported in the registry record.
The protocol description discusses a 30% reduction and gives a planning confidence-interval statement: for detecting a 30% difference, it describes a 95% confidence interval between 204 ng/ml and 290 ng/ml, or an 18-42% reduction in sVCAM. These figures are part of the investigators’ design rationale. They are not the confidence interval for the observed group comparison, and should not be read as uncertainty around the posted outcome values. The record’s statement that the lower limit is clinically relevant is also part of that rationale, rather than a conclusion from a reported comparative analysis.
There is no reported secondary outcome result in the record. Thus, the available statistical interpretation is limited to the endpoint definition, the two group summaries, and the stated design rationale. The record does not explain whether the posted summaries include all randomized participants, how missing outcome measurements were handled, whether covariates were included, or how possible confounders were addressed. A cautious reading distinguishes the observed summaries from the planned detectable effect and from any unreported inferential analysis. Neither the design target nor the group values alone establish a clinical effect.
9. Statistical Methods Explained
The statistical information in the registry record is limited. It describes the trial as randomized, triple-masked, and parallel-group, identifies the primary endpoint and its summary measure, and includes a design rationale for detectable differences. It does not report a detailed analysis plan or an inferential comparison of the two groups. The following points explain how to read the reported methods without treating undocumented procedures as known.
What does random allocation contribute?
In general, random allocation is used to make treatment assignment independent of participants’ measured and unmeasured characteristics on average. This supports a fair comparison between groups, although randomization does not guarantee that groups will be balanced in a particular trial, especially when the study is small. The record identifies randomized allocation but does not report the sequence-generation method, the way assignment was concealed, or checks of baseline balance. Those details are not reported in the registry record.
A parallel-group design means that participants are assigned to one study group rather than being described as crossing between treatments. The record identifies a parallel model and describes the two additions to hydroxyurea. It does not provide further information about adherence, crossover, or treatment discontinuation. Triple masking indicates that the registry classifies the trial as triple-masked, but the record does not specify which parties were masked or how masking was maintained.
Why report a median and inter-quartile range?
In general, the median is the midpoint of ordered observations: half of the observations lie at or below it and half at or above it. The inter-quartile range describes the spread of the middle portion of the observations. These summaries can be useful when a distribution is skewed or contains unusually high or low values, because they are less influenced by extreme observations than the mean and standard deviation. This is a general explanation, not a claim about the distribution of sVCAM in this trial.
The registry identifies the primary measure as a median and the dispersion as an inter-quartile range. It does not provide the inter-quartile range values in the outcome fields; the posted lower and upper bounds are not explained in the outcome description. It would therefore be inappropriate to assume those bounds are the inter-quartile range, a confidence interval, or another particular measure of uncertainty. The record also does not say whether the group summaries are based on raw changes or a modeled estimate.
What does a confidence interval mean?
In general, a confidence interval expresses uncertainty around an estimated quantity under a statistical procedure. A narrower interval indicates greater precision under that procedure, while a wider interval indicates more uncertainty. It does not give the probability that a fixed treatment effect lies inside one particular interval. A confidence interval for a treatment contrast would be needed to assess the precision of that contrast, but no such comparative interval is reported for the posted outcome.
The primary outcome description instead gives a design-related confidence-interval statement tied to detecting a 30% difference. It specifies a 95% confidence interval between 204 ng/ml and 290 ng/ml, and characterizes that as an 18-42% reduction in sVCAM. Those are statements about the investigators’ planning rationale. They must not be mistaken for an interval calculated from the observed group summaries. The record does not report the method used to derive that planning interval.
How should the feasibility and planning statements be read?
The investigators describe the study as a feasibility trial and state that 25 participants in each group were planned to explore all three aims and potential confounders. They also describe a scenario with 17 participants in each group for detecting a 30% difference in sVCAM. These are design statements, not observed group results. The record does not provide a sample-size justification sufficient to assess all assumptions, nor does it report a formal power calculation beyond the description included in the primary outcome rationale.
General sample-size illustrations based on an observed effect are planning exercises, not observed power. Their output depends on assumptions about the effect to detect, the significance level, allocation, and the statistical approximation. The registry record describes a two-sided significance level of 0.05, equal allocation, and a normal approximation for such illustrations; it does not report a trial-specific analysis using those assumptions. An illustration cannot establish that the trial had adequate power for the actual treatment effect, and post hoc power should not replace an estimate with a confidence interval.
Why does over-dispersion matter?
In general, over-dispersion occurs when variability in observed data exceeds what a chosen statistical model expects. If a model assumes less variation than the data contain, standard errors can be too small and uncertainty can appear overstated in the results. Choosing an appropriate model therefore requires information about the outcome distribution and the analysis objective. The registry record does not describe a model for the sVCAM outcome or report whether over-dispersion was assessed. This general issue is relevant to statistical planning, but it cannot be used to infer which model the investigators used.
Finally, a formal randomized comparison would ordinarily report an effect estimate and a measure of its uncertainty, with any adjustment choices explained. The registry record does not report these for the primary endpoint. No adjusted or unadjusted treatment contrast, p-value, or confidence interval is listed. Interpretation should therefore remain with the stated endpoint and the posted group-level values, without reconstructing an undocumented analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies one primary outcome measure: change in sVCAM from baseline to eight weeks. It lists no secondary outcome results. The trial description refers to exploring all three aims and potential confounders, but it does not identify the other aims as posted outcomes or explain their analysis. The record does not report a multiplicity strategy, such as a hierarchy of outcomes or an adjustment for multiple comparisons. With no reported secondary results or formal primary comparison, the effect of any multiplicity procedure cannot be assessed.
Missing-data handling is not reported in the registry record. The record does not state how many participants had an observed primary endpoint, whether measurements were missing, why any data might be missing, or whether imputation or another method was used. The enrollment listing and outcome-group n values are not a substitute for a description of the analysis population. In particular, they do not establish which participants contributed to each reported summary or how missing observations were handled.
The registry record also does not report whether the primary analysis followed intention-to-treat principles, used a per-protocol population, or applied another population definition. It does not describe exclusions, protocol deviations, or covariate adjustment. These omissions limit assessment of the analysis population and the risk that analytic choices affected the results. They do not demonstrate that such issues occurred; they mean the relevant information is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Montelukast Added to Hydroxyurea | 4 | 24 | 16.7% |
| Placebo Added to Hydroxyurea | 2 | 22 | 9.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Montelukast Added to Hydroxyurea | 0 of 24 |
| Placebo Added to Hydroxyurea | 0 of 22 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Montelukast Added to Hydroxyurea | 10 of 24 |
| Placebo Added to Hydroxyurea | 12 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | Montelukast Added to Hydroxyurea | Placebo Added to Hydroxyurea |
|---|---|---|---|
| Pain | Blood and lymphatic system disorders | 2 of 24 | 2 of 22 |
| Acute Chest Syndrome | Blood and lymphatic system disorders | 2 of 24 | 0 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Montelukast Added to Hydroxyurea | Placebo Added to Hydroxyurea |
|---|---|---|---|
| Pain | Blood and lymphatic system disorders | 3 of 24 | 6 of 22 |
| Pain | Injury, poisoning and procedural complications | 3 of 24 | 2 of 22 |
| upper respiratory infection | Respiratory, thoracic and mediastinal disorders | 2 of 24 | 2 of 22 |
| diarrhea | Gastrointestinal disorders | 1 of 24 | 2 of 22 |
| penile pain/priapsm | Reproductive system and breast disorders | 1 of 24 | 1 of 22 |
| cough | Respiratory, thoracic and mediastinal disorders | 0 of 24 | 1 of 22 |
| Pain | Respiratory, thoracic and mediastinal disorders | 1 of 24 | 0 of 22 |
| headache | General disorders | 0 of 24 | 1 of 22 |
| ear injury | Ear and labyrinth disorders | 0 of 24 | 1 of 22 |
| scleral disorder | Eye disorders | 1 of 24 | 0 of 22 |
Serious events with the highest arm-level rate: pain (9.1%), acute chest syndrome (8.3%).
The adverse-event listing reports serious adverse events affecting 4 participants among 24 at risk in the montelukast-added-to-hydroxyurea group, and 2 among 22 at risk in the placebo-added-to-hydroxyurea group. It reports other adverse events affecting 10 among 24 at risk in the montelukast group and 12 among 22 at risk in the placebo group. The record reports 0 deaths in each group. These counts should be read with their listed at-risk denominators; no additional rates or comparative estimates are calculated.
The record lists Pain at 9.1% and Acute Chest Syndrome at 8.3% among its top serious-event terms. It does not specify in this listing how those term percentages map to groups or provide further context about event timing, severity, recurrence, or attribution. The adverse-event figures are descriptive. The registry record does not report a statistical comparison of safety outcomes, and these data alone do not establish whether differences between groups are meaningful. The at-risk counts in the safety listing also should not be assumed to define the analysis population for the sVCAM endpoint.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a completed randomized phase 2 feasibility study of montelukast added to hydroxyurea compared with placebo added to hydroxyurea. It defines a primary biomarker endpoint and posts group-level outcome values at baseline to eight weeks. Those elements allow readers to understand what was compared and what measurement was designated primary. The outcome entries do not, however, give a formal estimate of the randomized treatment contrast or its precision.
The primary outcome description includes a target reduction and a planning rationale. The stated 30% reduction and associated confidence-interval discussion describe what investigators considered when designing the study; they are not proof that the target was observed. Likewise, the posted medians do not by themselves answer whether the treatment groups differed beyond what could be expected from sampling variability. A comparative estimate with uncertainty and a clear account of the analysis would be needed for that assessment, and these are not reported in the registry record.
The record also does not establish how representative the study population was, how completely participants followed treatment, how missing outcome data were handled, or whether potential confounders were included in an analysis. A feasibility study can inform whether a study approach is practicable, but the record’s description alone does not report detailed feasibility outcomes. The study’s size and phase label should not be used to infer the strength or direction of a treatment effect.
These limitations are about what the registry record reports, not proof that further analyses or information do not exist elsewhere. Based on the recorded outcome information, the appropriate conclusion is narrow: the trial has two posted group summaries for its primary biomarker endpoint, while the formal comparative result and its uncertainty are not reported in the registry record. The safety counts are also descriptive and should be interpreted separately from the biomarker outcome.
13. Why This Trial Matters Statistically
This trial illustrates a distinction that is central to interpreting clinical research: a protocol’s target effect is not the same as an observed treatment effect. The investigators described a 30% reduction in sVCAM as a design target and discussed the precision they expected for detecting such a difference. Those statements explain the study’s rationale, but they do not replace an estimate based on the posted results. Keeping planning assumptions separate from observed comparisons prevents design language from being mistaken for evidence of an outcome.
It also highlights why group summaries and comparative inference serve different purposes. Medians describe the center of each group’s observed outcome distribution, while a treatment contrast directly estimates the difference between assigned strategies. An uncertainty interval around that contrast would help readers judge its precision. The registry record provides group-level values but does not report that comparative estimate, a confidence interval for it, or a p-value. Statistical interpretation must reflect that gap rather than create a comparison from incomplete reporting.
The trial’s feasibility framing is relevant as well. Design aims can include exploration of multiple aims and potential confounders, while the posted registry outcome is limited to the primary sVCAM measure. Without a reported analysis plan, secondary results, or analysis population, readers cannot assess how those broader aims were addressed. These are important reporting distinctions even when a study is randomized and masked.
Finally, the safety listing shows why denominators and context matter. Counts of affected participants are informative as descriptive summaries, but without fuller event definitions and comparative analyses they do not support broad conclusions about relative safety. The record encourages a disciplined reading: identify the design, endpoint, summaries, and missing inferential details separately, and avoid treating a feasibility study’s design target as a demonstrated clinical 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.
Several trial-specific limitations follow from the registry record’s level of detail. The primary endpoint is a biomarker change over baseline to eight weeks. The record does not report a clinical endpoint alongside it, nor does it describe how sVCAM relates to clinical outcomes in this study. The results therefore address the recorded biomarker measure rather than a reported clinical outcome.
The record identifies the outcome summary as a median and inter-quartile range, but the posted outcome listing does not state the inter-quartile range values. It gives lower and upper bounds without defining them in the outcome description. The record also provides no formal between-group effect estimate, uncertainty interval, or p-value. As a result, the precision and inferential interpretation of the primary comparison cannot be assessed from the posted outcome information.
Although the record states randomized allocation and triple masking, it does not describe sequence generation, allocation concealment, masking procedures, adherence, or protocol deviations. It does not report the analysis population, missing-data handling, covariate adjustment, or whether the analysis followed intention-to-treat principles. The description mentions potential confounders, but it does not state how they were handled.
The study is described as a feasibility trial, and the primary outcome rationale includes planned group sizes and a detectable-difference discussion. The registry record does not report enough detail to independently assess the assumptions behind that rationale. The posted safety summary likewise lacks event timing, attribution, and a formal comparative analysis. These reporting gaps limit how confidently the outcome and safety summaries can be generalized or interpreted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia — NCT01960413.
- Registry record last updated 2019-03-26; status last verified 2019-03.
- Results first posted 2019-03-26.
- 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.
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18. Record Summary
NCT01960413 is a completed randomized, triple-masked, parallel-group phase 2 feasibility study sponsored by Vanderbilt University Medical Center. It compared daily oral montelukast plus current hydroxyurea with daily oral placebo plus current hydroxyurea for eight weeks in people with sickle cell anemia, including HbSS or HbSβ-thalassemia0.
The primary endpoint was change in sVCAM from baseline to eight weeks, measured in ng/mL and summarized by median and inter-quartile range. The registry lists outcome values of -3.2 for the montelukast group and 4.17 for the placebo group, but does not report a formal comparative analysis or its uncertainty. The record’s design discussion of a 30% reduction is a planning rationale, not an observed treatment result. Adverse-event counts are posted descriptively, with 0 deaths reported in each group. Details about missing data, analysis populations, and the statistical plan are not reported in the registry record.