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 Study of Propranolol as Anti-Adhesive Therapy in Sickle Cell Disease (SCD) (NCT01077921), a randomized phase 2 study. The primary outcome is SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01077921 |
| Phase | Phase 2 |
| Condition | Sickle Cell Disease |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Laura M. De Castro, MD |
| Results posted | Yes |
2. Clinical Question
Population
People with sickle cell disease were eligible according to the study summary if they were homozygous for Hb S or had HbSB0 thalassemia. The registry records an enrollment of 31; the summary describes a planned study of up to 60 patients.
Intervention
Propranolol was the active treatment. The summary describes a standard dose of 40 mg every 12 hrs for 6 weeks, followed by a 2-week washout before the other treatment period.
Comparator
Placebo was the comparator. Participants were to receive the other treatment modality after the washout, according to the randomized crossover design described in the summary.
Primary question
The primary outcome concerns change in sickle red blood cell adhesion to cultured endothelial cells, comparing epinephrine-stimulated cells with sham-treated cells. The registry describes measurements over week 0 to 6 and week 8 to 14, but does not report a numerical treatment effect.
The stated primary objective was to establish the safety and efficacy of long-term propranolol therapy as an anti-adhesive therapy for sickle cell disease. The primary endpoint is a laboratory measure of adhesion, rather than a clinical event such as hospitalization. The study also listed secondary objectives concerning soluble markers of endothelial activation and dysfunction, and a correlative science objective concerning genetic polymorphisms and response.
The clinical question therefore has two parts: whether the measured adhesion changes during propranolol treatment relative to placebo, and how precisely any such difference can be estimated. The posted results do not provide the endpoint values, treatment contrast, uncertainty interval, or test result needed to answer those questions. The registry record also does not report a numerical result for the secondary objectives.
3. Trial Design
The registry identifies this as a phase II, randomized, crossover study of propranolol and placebo in sickle cell disease. Enrollment is recorded as 31, while the study summary describes a plan for up to 60 patients. The summary says that participants would receive either propranolol or placebo for 6 weeks, have a 2-week washout, and then receive the other treatment. This arrangement allows each participant to receive both treatment modalities, with the treatment order assigned randomly.
The crossover structure is relevant to interpretation because outcomes can be compared within the same participant as well as across treatment periods. A participant's outcome under one treatment may be related to their outcome under the other; an analysis that recognizes this pairing can account for some stable differences between participants. Period effects, carryover from the earlier treatment, and changes over time can also matter in crossover studies. The registry record does not report how these features were handled in the analysis, or whether carryover was assessed.
The study summary calls the trial open label, whereas the registry design fields list triple masking. This discrepancy is not resolved in the registry record. The record lists propranolol and placebo as interventions and describes randomized treatment order, but does not provide further details about which study roles were masked or how masking was maintained.
The listed primary outcome timeframe is week 0 to 6 and week 8 to 14. The study status is completed, with a start date of 2010-06 and primary completion date of 2013-12. These dates and the completed status do not themselves establish that the outcome results were posted. No primary endpoint estimate or analysis result is 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.
Before assignment: Eighty-four patients were approached for the study, of those 28 declined to participate, 14 remained undecided. Forty-two patients consented. Thirthy-one of those consenting were enrolled and 27 randomized to the study.
First Intervention
| Stage | Propranolol-first | Placebo-first |
|---|---|---|
| STARTED | 14 | 13 |
| COMPLETED | 13 | 12 |
| NOT COMPLETED | 1 | 1 |
Washout
| Stage | Propranolol-first | Placebo-first |
|---|---|---|
| STARTED | 13 | 12 |
| COMPLETED | 13 | 10 |
| NOT COMPLETED | 0 | 2 |
Second Intervention
| Stage | Propranolol-first | Placebo-first |
|---|---|---|
| STARTED | 13 | 10 |
| COMPLETED | 13 | 9 |
| NOT COMPLETED | 0 | 1 |
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 | Propranolol-first | Placebo-first | Total |
|---|---|---|---|---|
| Participants analysed | 14 | 13 | 27 | |
| Age, Continuous | years | 34.2 (29.4 to 40.8) | 26.1 (24.7 to 32.7) | 30.4 (25.6 to 39.6) |
| Sex: Female, Male: Female | Participants | 8 | 9 | 17 |
| Sex: Female, Male: Male | Participants | 6 | 4 | 10 |
| Region of Enrollment: United States | participants | 14 | 13 | 27 |
6. Primary Endpoint
The registry lists the primary outcome as SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment, measured over Week 0 to 6 and week 8 to 14.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Percentage of total RBC |
| Endpoint classification | Continuous Endpoint |
The primary outcome is SS RBC adhesion, described as the stickiness of sickle red blood cells measured in vitro. The registry says that cells are assessed for adhesion to cultured endothelial cells using a flow chamber. It specifies a comparison between epinephrine-treated, stimulated cells and sham-treated, unstimulated cells at 1 dyne/cm2. The outcome is expressed as a percentage of total RBC, with the mean as the listed summary measure and standard deviation as the listed dispersion measure.
The endpoint concerns change from baseline to post-intervention across week 0 to 6 and week 8 to 14. The rationale in the study summary is that propranolol might change baseline adhesion and epinephrine-stimulated adhesion. This laboratory assay is intended to measure a biological process relevant to the study's anti-adhesive objective. It is not, by itself, a direct measure of symptoms, clinical events, or long-term outcomes.
For the treatment question, the key statistical quantity would ordinarily be a contrast in adhesion change between propranolol and placebo, with uncertainty around that contrast. However, the registry record does not report the observed means, standard deviations, contrast, confidence interval, or p-value. The outcome description alone therefore identifies what was intended to be measured, but not what the study found.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and design, but it does not give a numerical result for the primary adhesion endpoint. It lists an outcome definition, unit, summary measure, dispersion measure, and assessment periods; it does not report outcome values or an estimated difference between propranolol and placebo. A direction or magnitude of effect cannot be described from the information reported in the registry record.
The record also reports zero analyses. This means there is no posted analysis result from which to assess statistical significance, precision, or consistency with the study objectives. A p-value, confidence interval, or treatment-effect estimate is not reported in the registry record. The completed status and the fact that 31 participants were enrolled are not substitutes for an outcome analysis: neither indicates the direction or size of any treatment contrast.
The study's crossover design could support a within-participant comparison, but the effect estimate would depend on the analysis method and the observed data. For example, the interpretation would need to account for the relationship between the two treatment periods and consider whether period or carryover effects are relevant. Those analysis details and results are not reported in the registry record, so it is not possible to determine whether the posted outcome, if collected, was analyzed in a way that reflects the crossover structure.
The primary endpoint also compares epinephrine-stimulated and sham-treated cells. The registry description indicates that there are multiple categories or time points, and the endpoint has not been reduced to one comparison in the posted results. Consequently, there is no single primary contrast to interpret from the record. It would be inappropriate to select one time point, cell condition, or treatment comparison and present it as the study's overall primary finding.
Eight secondary outcomes are named, including plasma levels of soluble endothelial markers, hemoglobin, hematocrit, lactate dehydrogenase, and oxygen saturation. The record does not report numerical results for these measures either. Their presence indicates that the study included more than one outcome domain, but does not show whether any outcome changed or whether results were consistent across domains.
The adverse-event entries are descriptive counts. They report serious events and other events in the propranolol and placebo groups, but do not establish a comparative safety effect. The record does not describe the event-analysis method, exposure-adjusted rates, uncertainty, or a statistical test. Serious adverse-event counts should therefore be read as counts recorded for the listed groups, not as a standalone estimate of relative risk.
Overall, the posted record permits a description of the trial's intended question, design, endpoint, and selected event counts. It does not permit an efficacy conclusion or a precise comparison of treatment outcomes. This is a limitation of the reported results, not evidence that the measured effect was absent or present.
9. Statistical Methods Explained
Statistical interpretation begins with the estimand: the quantity a study aims to estimate. For this study, the primary objective concerns the change in SS RBC adhesion during propranolol treatment compared with placebo, with epinephrine-stimulated and sham-treated cells included in the endpoint description. The registry identifies the outcome as continuous, summarized by a mean with standard deviation. It does not report an estimated contrast, so the estimand cannot be assigned a numerical value from the posted results.
What does a mean and standard deviation describe?
In general, a mean describes the central value of a set of measurements. A standard deviation describes how spread out individual measurements are around that mean. The standard deviation is not the same as the uncertainty in the estimated mean or treatment contrast. A confidence interval would usually express the precision of an estimate by giving a range of values compatible with the data and analysis assumptions. No mean, standard deviation, or confidence interval for the primary endpoint is reported in the registry record.
Why does the crossover design matter?
In general, a crossover trial assigns treatment sequences so participants receive more than one treatment over separate periods. This can make each participant their own comparator, which may help account for stable characteristics that differ between participants. It also requires attention to within-participant correlation: measurements from the same person are usually not independent. The analysis may also need to distinguish treatment effects from period effects, and consider whether the first treatment could affect outcomes during the next period. The study summary describes a washout period between treatments, but the registry record does not report an analysis of carryover or the statistical model used.
Random allocation concerns assignment to treatment order. It does not, by itself, ensure that the final analysis has accounted for the crossover structure or that missing measurements are balanced. The registry records randomization and a crossover model, but does not report allocation procedures, treatment-sequence counts, analysis populations, or how repeated measurements were incorporated. These details are needed to assess the implementation and analysis more fully.
How should statistical significance and precision be read?
In general, a p-value describes how incompatible the observed data are with a specified null model, under the assumptions of the statistical test. It does not measure the probability that a treatment effect is true, and it does not describe the size or clinical importance of an effect. A confidence interval is useful because it displays the range of effect sizes consistent with the data and method, rather than reducing interpretation to a threshold. Neither a p-value nor a confidence interval for the primary outcome is reported in the registry record. Statistical significance and precision therefore cannot be assessed.
For a continuous outcome, the scale also matters. Here, adhesion is expressed as a percentage of total RBC. A treatment contrast would need to be interpreted in that scale and in the context of the assay. The registry does not report the observed distribution, any transformation, or whether model assumptions were checked. General concerns such as skewness, influential observations, and non-constant variability may matter for continuous outcomes, but whether any of these applied in this study is not reported in the registry record.
What can the planning illustrations show?
In general, sample-size planning asks how much information a future study would need to detect a specified effect with a chosen error rate and power, under stated assumptions. Such planning is distinct from an analysis of the enrolled participants. The registry's planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and fractions of the observed effect. These are planning assumptions, not a report of the study's own design justification. The record does not report a trial-specific sample-size justification. Any sample-size illustration is not observed power and should not be read as evidence that the completed study had a particular probability of detecting an effect.
The stated illustration is based on the observed effect, but the primary outcome's observed effect is not reported in the registry record. The record also does not list numerical sample-size illustration results in the information available for this analysis. A sample-size calculation cannot repair the absence of an effect estimate, nor can it establish what happened in the trial.
Why can over-dispersion matter?
In general, over-dispersion means that observed variability is greater than a model assumes. If ignored, standard errors can be too small and intervals too narrow, making results appear more precise than they are. The primary endpoint is continuous and summarized with a standard deviation, rather than a count model; the registry record does not report evidence of over-dispersion or an analysis addressing it. This concept is relevant generally, but there is no basis in the posted results to say that over-dispersion affected this study.
The registry's primary outcome description includes multiple conditions or time points, and the record indicates that it was not reduced to one comparison. A reader would need the prespecified contrast and model, as well as the results, to judge how the primary objective was evaluated. Those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures and names multiple secondary outcomes, while the primary endpoint description includes stimulated and sham-treated cells and more than one assessment period. Testing several outcomes or contrasts can increase the chance that at least one result appears statistically notable by chance. In general, a multiplicity plan may define one primary comparison, adjust inference across selected tests, or distinguish confirmatory from exploratory analyses. The registry record does not report a multiplicity plan, so it is not possible to determine how multiple outcomes or contrasts were handled.
The record reports zero analyses and does not provide a primary endpoint estimate. It also does not report results for the listed secondary outcomes. Consequently, the posted information does not show which comparisons were analyzed, whether outcome selection affected interpretation, or whether any adjustment for multiple testing was used.
Missing-data methods and analysis populations are also not reported in the registry record. The enrollment count is 31, but the record does not state how many participants contributed endpoint measurements in each period, whether all randomized participants were analyzed, or how missing measurements were treated. In a crossover study, missing data in either treatment period can affect the paired comparison. General methods include analyzing available paired observations under stated assumptions or using models that can incorporate incomplete repeated measurements; which approach, if any, was used is not reported.
The record does not report an intention-to-treat definition, a per-protocol population, exclusions from analysis, or sensitivity analyses for missing data. These omissions limit assessment of how the enrolled participants relate to the analyzed sample and how robust any result would be to missingness. With no posted efficacy analysis, they also prevent evaluation of whether the analysis population matched the intended treatment comparison.
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 |
|---|---|---|---|
| Propranolol | 4 | 27 | 14.8% |
| Placebo | 3 | 27 | 11.1% |
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 |
|---|---|
| Propranolol | 22 of 27 |
| Placebo | 19 of 27 |
Most frequent serious adverse event terms
| Event term | Organ system | Propranolol | Placebo |
|---|---|---|---|
| Vaso-occlusive crisis resulting in hospitalization | Musculoskeletal and connective tissue disorders | 4 of 27 | 3 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Propranolol | Placebo |
|---|---|---|---|
| Headache | Nervous system disorders | 8 of 27 | 8 of 27 |
| Pain Crisis | Musculoskeletal and connective tissue disorders | 6 of 27 | 4 of 27 |
| Fatigue | General disorders | 4 of 27 | 4 of 27 |
| Cough | Respiratory, thoracic and mediastinal disorders | 6 of 27 | 1 of 27 |
| Dizziness | Nervous system disorders | 1 of 27 | 5 of 27 |
| Pain, Musculoskeletal | Musculoskeletal and connective tissue disorders | 1 of 27 | 4 of 27 |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | 1 of 27 | 4 of 27 |
| Vaso-occlusive Crisis | Musculoskeletal and connective tissue disorders | 2 of 27 | 2 of 27 |
| Abdominal Paiin | Gastrointestinal disorders | 1 of 27 | 2 of 27 |
| Diarrhea | Gastrointestinal disorders | 1 of 27 | 2 of 27 |
Serious events with the highest arm-level rate: vaso-occlusive crisis resulting in hospitalization (14.8%).
The adverse-event record lists 27 participants at risk in each treatment group. Serious adverse events are recorded for 4 participants in the propranolol group and 3 in the placebo group. Other adverse events are recorded for 22 participants in the propranolol group and 19 in the placebo group. These are counts for the groups as listed; they are not, on their own, estimates of a treatment effect.
The registry names “Vaso-occlusive crisis resulting in hospitalization” as the top serious term and reports 14.8%. The entry does not specify in the information available whether that percentage applies to one treatment group or to a combined population, so it should not be assigned to a particular group. The death counts are not reported in the registry record.
In general, event counts are easier to interpret when the record also describes observation time, event definitions, severity and attribution rules, and a comparative analysis with uncertainty. Those details are not reported in the registry record. The entries also do not indicate whether multiple events could occur in one participant or how events during the crossover periods were attributed. The counts should therefore be read descriptively and not as proof of a safety difference or the absence of one.
12. What the Result Does, and Does Not, Mean
The posted information identifies a randomized phase II crossover study that compared propranolol with placebo and focused on a laboratory measure of sickle red blood cell adhesion. It also records selected adverse-event counts and lists secondary biomarker outcomes. These details clarify what the investigators intended to study and provide some information about the trial's design and reporting.
The information does not establish the size or direction of a treatment effect on adhesion. No outcome values, treatment contrast, confidence interval, or p-value are reported in the registry record. The completed study status and enrollment of 31 do not substitute for those results. In particular, the record cannot show whether propranolol reduced, increased, or left unchanged the measured adhesion outcome.
Even if a laboratory endpoint had a reported difference, general interpretation would distinguish a change in an assay from a change in clinical outcomes. The stated endpoint measures adhesion to cultured endothelial cells under specified assay conditions; it is not itself a measure of patient experience or a clinical event. The record lists biomarker outcomes and safety objectives, but does not report their numerical results either.
The serious and other adverse-event entries are counts, not a complete comparative safety analysis. Differences in counts cannot be interpreted without information on exposure, event ascertainment, analysis, and uncertainty. The listed top serious term is not linked to a particular treatment group in the information available. As a result, the posted safety entries do not establish a comparative safety conclusion.
The appropriate conclusion is limited: the registry describes a study designed to examine propranolol, placebo, and an adhesion assay in people with sickle cell disease, but the posted record does not provide the statistical results needed to determine what the study found. This absence of reported results should not be interpreted as evidence for either benefit or no effect.
13. Why This Trial Matters Statistically
This trial is statistically interesting because its crossover structure makes the choice of analysis particularly important. Each participant was intended to receive both propranolol and placebo in separate periods, with a washout between them. A well-specified analysis can use the within-participant comparison while accounting for repeated observations and treatment period. Without the model and results, however, the design label alone cannot show how much information the study generated or how precisely its treatment contrast was estimated.
The primary endpoint also combines an assay-based measure with stimulated and sham-treated conditions over more than one assessment period. A clear estimand is needed to specify which treatment contrast, time point, and cell condition answer the primary question. The registry record does not reduce the outcome description to one comparison or report an analysis result. That makes it difficult to evaluate whether the reported outcome structure maps to a single prespecified hypothesis.
The study lists several secondary biomarkers in addition to its primary objective. Multiple outcomes can be useful for describing different biological processes, but they also raise questions about multiplicity, prioritization, and exploratory interpretation. The record does not report the statistical plan or results needed to assess these issues.
Finally, the difference between the open-label description in the study summary and the triple-masking design field illustrates why design details should be reconciled before interpreting results. The record does not resolve that difference. Taken together, the design features make the study a useful example of why interpretation requires more than a trial label or an enrollment count: it also depends on a defined estimand, transparent analysis, and posted estimates with measures of uncertainty.
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 registry record contains a primary endpoint description but no numerical primary outcome results and no analyses. It therefore does not support an estimate of the propranolol-placebo contrast, an assessment of precision, or a statistical test of the primary question. The record also does not report results for the listed secondary outcomes.
There is a reporting inconsistency in the design description: the study summary calls the trial open label, while the registry design fields list triple masking. The record does not explain which description reflects study conduct or clarify who was masked. This leaves uncertainty about the masking procedures.
The summary describes a planned enrollment of up to 60, while the registry reports enrollment of 31. The registry does not explain the relationship between the planned and recorded enrollment or give a sample-size justification. It also does not report the number of participants with usable measurements in each treatment period, exclusions, missing-data handling, or the analysis population.
For the crossover design, the statistical model, treatment-sequence details, period effects, and assessment of possible carryover are not reported in the registry record. The time frame and definitions used to collect adverse events, and the attribution of events to treatment periods, are also not described in the information available. These limitations make the reported event counts difficult to compare beyond their descriptive presentation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Propranolol as Anti-Adhesive Therapy in Sickle Cell Disease (SCD) — NCT01077921.
- Registry record last updated 2015-01-22; status last verified 2015-01.
- Results first posted 2015-01-22.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed randomized phase II crossover study of propranolol and placebo in sickle cell disease. Enrollment is recorded as 31. The study summary describes treatment for 6 weeks, a 2-week washout, and crossover to the other treatment. The primary endpoint is change in SS RBC adhesion measured in vitro, expressed as a percentage of total RBC and summarized by a mean and standard deviation.
The record lists multiple secondary biomarker outcomes and adverse-event counts. It reports zero analyses and does not report numerical results for the primary endpoint or secondary outcomes. The study summary says open label, while the design field lists triple masking; this discrepancy is not resolved. The registry record therefore supports a description of the study design and outcome definitions, but not an efficacy estimate or a comparative safety conclusion.