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 Prasugrel Versus Placebo in Adult Sickle Cell Disease (NCT01167023), a randomized phase 2 study. The primary outcome is Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention During the Treatment Duration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01167023 |
| Phase | Phase 2 |
| Condition | Sickle Cell Anemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 62 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Adults with sickle cell disease were eligible for this phase 2 trial. The registry lists sickle cell anemia as the condition and reports an enrollment of 62 participants. The primary analysis population was the safety population: randomized participants who took at least 1 dose of study medication, analyzed according to the treatment they actually received.
Intervention
The study compared prasugrel with placebo. The posted primary and secondary results identify a 5 mg prasugrel group. The arm description also refers to a 7.5 mg dose under specified conditions, but the description is incomplete in the registry record; the results presented are for the 5 mg group.
Comparator
The comparator was placebo. The registry describes a randomized, parallel-group study with quadruple masking. Participants were followed through a 30-day treatment duration for the primary endpoint and several secondary outcomes.
Primary question
The primary question was whether hemorrhagic events requiring medical intervention occurred during the treatment duration. The registry defines medical intervention as medical attention resulting in therapy or further investigation. The analysis reports no such events in either group among participants in the safety population.
3. Trial Design
This was a phase 2, randomized, parallel-group study comparing prasugrel with placebo in adults with sickle cell disease. The registry describes the study as quadruple-masked and reports that 62 participants were enrolled. The listed study start was 2010-07, primary completion was 2011-06, and the current status is completed.
The primary outcome covered baseline through 30 days and measured the percentage of participants with hemorrhagic events requiring medical intervention. The registry defines an event requiring intervention as medical attention resulting in therapy or further investigation during the 30-day treatment duration. The stated purpose was to assess safety by monitoring the rate and severity of these events compared with placebo.
The primary results use a safety population consisting of randomized participants who took at least 1 dose of study medication. Participants were analyzed according to the treatment they actually received. The reported group sizes for this endpoint were 19 for placebo and 41 for 5 mg prasugrel. The outcome reports no events in either group.
The registry includes secondary outcomes concerning pain, pain-related medical attention, and platelet measures. The outcome list also includes hemorrhagic treatment-emergent adverse events. Some secondary outcomes have posted numerical results, while other outcome measures do not have numerical results in the material described by the registry record. Details of the allocation procedure, the masking roles, the planned sample-size rationale, and the study's full statistical plan 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.
Overall Study
| Stage | 7.5 mg Prasugrel | Placebo | 5 mg Prasugrel |
|---|---|---|---|
| STARTED | 0 | 21 | 41 |
| Received at Least 1 Dose of Study Drug | 0 | 19 | 41 |
| COMPLETED | 0 | 18 | 39 |
| NOT COMPLETED | 0 | 3 | 2 |
Reasons for not completing this period:
| Reason | 7.5 mg Prasugrel | Placebo | 5 mg Prasugrel |
|---|---|---|---|
| Lost to Follow-up | 0 | 1 | 1 |
| Screen Failure | 0 | 1 | 0 |
| Sponsor Decision | 0 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety population: All randomized participants who took at least 1 dose of study medication. Participants were analyzed according to the treatment they actually received.
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 | Placebo | 5 mg Prasugrel | Total |
|---|---|---|---|---|
| Participants analysed | 21 | 41 | 62 | |
| Age Continuous | years | 31.52 (SD 8.20) | 32.88 (SD 8.60) | 32.42 (SD 8.42) |
| Sex: Female, Male: Female | Participants | 9 | 21 | 30 |
| Sex: Female, Male: Male | Participants | 12 | 20 | 32 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 21 | 40 | 61 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| 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 | 21 | 40 | 61 |
| Race (NIH/OMB): White | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: Canada | participants | 3 | 8 | 11 |
| Region of Enrollment: United States | participants | 18 | 33 | 51 |
| Sickle-Cell Genotype: Hb S ß+ thalassemia genotype | participants | 2 | 4 | 6 |
| Sickle-Cell Genotype: Hb S ß0 thalassemia genotype | participants | 1 | 2 | 3 |
| Sickle-Cell Genotype: Hb SC genotype | participants | 5 | 10 | 15 |
| Sickle-Cell Genotype: Hemoglobin SS (Hb SS) genotype | participants | 13 | 24 | 37 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention During the Treatment Duration, measured over Baseline through 30 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint measured the percentage of participants with a hemorrhagic event requiring medical intervention during the treatment duration, defined as baseline through 30 days. The registry's event definition requires medical attention that results in therapy or further investigation. This is narrower than counting every report of bleeding: the endpoint focuses on events meeting the stated intervention criterion.
A safety endpoint of this kind is used to describe whether a clinically consequential event was observed during exposure to the study medication. The registry states that assessing prasugrel safety by monitoring the rate and severity of such events compared with placebo was the trial's purpose. The recorded primary results show zero events among 19 placebo participants and zero among 41 participants assigned to the 5 mg prasugrel group in the safety population.
These observations describe what occurred in this trial during its specified follow-up. With no observed events in either group, the estimated risk difference is 0.0, with reported limits of 0.0 and 0.0. That result is a description of the observed data, not evidence that the underlying risks are exactly equal. The number of participants and the absence of events constrain what can be learned about uncommon outcomes. The registry does not report additional details about endpoint adjudication or the handling of events that could not be classified.
7. Results Posted in the Registry
- 5 mg Prasugrel: 0.0% (0/41) versus 0.0% (0/19) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
Risk difference: 5 mg Prasugrel
95% CI: 0.0 to 0.0 percentage points
Recalculated from the posted summary statistics
8. Secondary Efficacy Endpoints
The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| Percentage of Days With Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration | Continuous Endpoint | Mean difference | -24.53 (-47.85 to -1.21) | 47 per arm |
| Percentage of Participants With Pain Events Related to Sickle Cell Disease (SCD) Requiring Medical Attention During the Treatment Duration | Binary Endpoint | Risk difference | -14.3 pts (-39.6 to 10.9) | 159 per arm |
| Platelet Reactivity Index (PRI) Measured by Vasodilator-Associated Stimulated Phosphoprotein (VASP) at 30 Days | Continuous Endpoint | Mean difference | -24.05 (-35.85 to -12.26) | 10 per arm |
Percentage of Days With Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
- Result:
- 5 mg Prasugrel: mean 39.04 versus 63.57 on control; difference -24.53 (95% CI -47.85 to -1.21), standardized effect d = -0.58; z-test p = 0.039.
- Interpretation:
- The 95% confidence interval excludes no difference, so the mean is statistically lower for 5 mg Prasugrel than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
Percentage of Participants With Pain Events Related to Sickle Cell Disease (SCD) Requiring Medical Attention During the Treatment Duration
- Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
- Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
- Result:
- 5 mg Prasugrel: 22.5% (9/40) versus 36.8% (7/19) on control; risk difference -14.3 percentage points (95% CI -39.6 to 10.9), risk ratio 0.61 (0.27–1.39); unadjusted two-proportion z-test p = 0.247.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 5 mg Prasugrel and the control. The interval gives the range of effects that remain compatible with the data.
Platelet Reactivity Index (PRI) Measured by Vasodilator-Associated Stimulated Phosphoprotein (VASP) at 30 Days
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
- Result:
- 5 mg Prasugrel: mean 50.79 versus 74.84 on control; difference -24.05 (95% CI -35.85 to -12.26), standardized effect d = -1.30; z-test p = <0.001.
- Interpretation:
- The 95% confidence interval excludes no difference, so the mean is statistically lower for 5 mg Prasugrel than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
The secondary outcomes span pain-related measures and platelet measures, so they address more than one kind of question. The posted numerical results do not all point to the same degree of statistical certainty: the unadjusted pain-days calculation and the platelet reactivity comparison have p-values below 0.05, while the pain-events comparison does not. For pain days, the registry's ANCOVA result also differs in its estimate and p-value from the unadjusted recalculation. These outcomes should therefore be interpreted by endpoint and method, not combined into a single overall conclusion.
The secondary results do not change the primary endpoint finding: no hemorrhagic events requiring medical intervention were recorded in either group. They also do not resolve the uncertainty about the primary safety comparison, because they measure different outcomes. Platelet reactivity is a laboratory measure, while the pain outcomes describe participant experiences or events requiring medical attention. A difference in one measure cannot be assumed to demonstrate a difference in another.
Several secondary outcomes are listed in the registry, but numerical results are not posted for every outcome. Their results are not reported in the registry record, so no direction or size of difference can be inferred for them. The record includes multiple outcome measures and analyses, but whether the secondary hypotheses were prespecified in a hierarchy or adjusted for multiple testing is not reported.
General statistical explanation: testing multiple outcomes increases the chance that at least one result will appear statistically notable by chance if each is interpreted in isolation. An unadjusted p-value does not account for that broader set of comparisons. Secondary outcomes can still be informative, but their estimates, uncertainty, analysis methods, and place in the trial's outcome hierarchy matter. In this record, the missing multiplicity plan and the difference between unadjusted and model-based pain analyses counsel against treating any one secondary p-value as definitive.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Percentage of Participants With Hemorrhagic Treatment-Emergent Adverse Events (TEAEs) During the Treatment Duration
- Percentage of Days With Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration
- Percentage of Participants With Pain Events Related to Sickle Cell Disease (SCD) Requiring Medical Attention During the Treatment Duration
- Platelet Reactivity Index (PRI) Measured by Vasodilator-Associated Stimulated Phosphoprotein (VASP) at 30 Days
- Intensity of Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration
- P2Y12 Reaction Units (PRU) as Measured by Accumetrics VerifyNow® P2Y12 (VN P2Y12) at 30 Days
9. Statistical Interpretation
For the primary endpoint, the registry reports no hemorrhagic events requiring medical intervention in either group: 0 of 19 participants receiving placebo and 0 of 41 receiving 5 mg prasugrel. The posted risk difference is 0.0, with a confidence interval from 0.0 to 0.0. Thus, the recorded data contain no observed between-group difference for this endpoint. Because neither group had an event, the result does not establish that the treatments have identical underlying risks or that such events cannot occur.
Secondary results address different questions and should be read separately from the primary safety outcome. For percentage of days with sickle cell disease-related pain, the unadjusted recalculation gives a mean difference of -24.53, with a confidence interval from -47.85 to -1.208 and p = 0.039. The registry also reports an ANCOVA least-squares mean difference of -11.26 with p = 0.304. These analyses use different approaches, so their estimates and p-values are not interchangeable. For pain events requiring medical attention, the unadjusted risk difference is -0.143, with a confidence interval from -0.396 to 0.109 and p = 0.247. The platelet reactivity index result is a mean difference of -24.05, with a confidence interval from -35.85 to -12.26 and p < 0.001; the registry's mixed-model analysis reports a least-squares mean difference of -24.051 and p < 0.001.
These secondary analyses are not substitutes for the primary safety endpoint. The registry does not report whether the secondary tests were adjusted for multiple comparisons, so individual unadjusted p-values warrant cautious interpretation, particularly when several outcomes are examined. A small p-value does not by itself establish clinical importance, and a non-small p-value does not establish that a difference is absent. Estimates, their uncertainty, the analysis method, and the endpoint's role in the study all matter.
Any sample-size illustrations based on observed effects are planning aids, not evidence about the probability that this completed trial would detect an effect. They rely on assumptions described with the illustrations and use observed effects as inputs. The primary endpoint's zero-event pattern also means these secondary planning calculations should not be read as a design justification for the safety comparison.
10. Statistical Methods Explained
General statistical explanation: A randomized comparison aims to assess how outcomes differ between groups while reducing systematic differences at assignment. Randomization does not guarantee that every characteristic is balanced in a modest-sized trial, and it does not eliminate uncertainty in the estimated treatment contrast. The registry identifies this study as randomized and parallel-group; the specific randomization method and any stratification are not reported in the registry record.
Binary outcomes and risk differences. The primary endpoint and the pain-events-requiring-medical-attention outcome are expressed as percentages of participants with an event. A risk difference describes the absolute difference between the event proportions in two groups. A value of 0 indicates equal observed proportions; a negative value means the proportion in the prasugrel group is lower than the placebo proportion under the stated subtraction direction. The primary endpoint has no observed events in either group, so its reported risk difference is 0.0. A zero observed difference does not determine the true risks, particularly when the outcome is uncommon.
Continuous outcomes and mean differences. Percentage of days with pain and platelet reactivity are measured on continuous scales. A mean difference compares group averages, with the sign depending on which group is subtracted from which. The unadjusted recalculation for pain days reports -24.53, while the platelet reactivity comparison reports -24.05. Such estimates describe average contrasts; they do not imply that every participant experienced a change of that size. The pain-days group summaries include standard deviations. The platelet reactivity group summaries are least-squares means with standard errors, rather than ordinary means with standard deviations.
Confidence intervals. General statistical explanation: a confidence interval conveys uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision in the estimate, while a wider interval indicates more uncertainty. For a difference, an interval that includes zero is compatible with no difference under the interval's method; an interval that excludes zero indicates that the data are less compatible with a zero difference under that method. This interpretation does not establish clinical importance, rule out bias, or prove a treatment effect.
p-values. General statistical explanation: a p-value measures how incompatible the observed data are with a specified null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The unadjusted pain-days calculation has p = 0.039, whereas the registry's ANCOVA analysis has p = 0.304. These are results from different analyses, so the distinction in method matters. The platelet reactivity recalculation and the registry's mixed-model result both report p < 0.001.
Adjusted analyses. ANCOVA is a model-based method for comparing group outcomes while accounting for covariates included in the model. A mixed model can account for specified dependencies in data, depending on its structure. The registry identifies the reported pain-days method as ANCOVA and the platelet reactivity method as Mixed Models Analysis. The covariates, model specifications, and assumptions are not reported in the registry record, so the exact adjustments cannot be reconstructed from the posted results.
Over-dispersion and distributional assumptions. General statistical explanation: over-dispersion occurs when observed variability in a count or binary outcome is greater than a model assumes. If not accounted for, standard errors can be too small and tests can appear more conclusive than the data warrant. For continuous outcomes, departures from a model's distributional assumptions can also affect uncertainty estimates. The registry record does not report a specific over-dispersion assessment for these outcomes.
Planning illustrations. The posted planning illustrations are based on observed effects and describe participants per arm for 80% or 90% power under stated assumptions: a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is a specified fraction of the observed effect. These are planning scenarios, not observed power, and they are not evidence that the original trial was designed using those assumptions. The trial's sample-size justification is not reported in the registry record.
Missing information and analysis sets. The primary endpoint specifies a safety population and actual-treatment analysis. Secondary group sizes vary by outcome, but the reasons for those differences and the handling of missing measurements are not reported in the registry record. General statistical explanation: missing data can affect an estimate when the likelihood of missingness is related to outcomes or participant characteristics. Without details on missingness and the analysis population for each secondary result, the extent of that influence cannot be assessed.
11. Confidence Intervals and Precision
The primary endpoint has a point estimate of 0.0 for the risk difference and reported confidence limits of 0.0 and 0.0. This reflects the posted calculation for groups with no observed events, but it should not be interpreted as proof that the underlying risks are known without uncertainty. With zero events in both groups, the data provide no observed contrast to distinguish the groups on this endpoint. The registry does not report a separate uncertainty method for interpreting the zero-event result.
For pain days, the unadjusted mean-difference interval runs from -47.85 to -1.208. It spans a range of possible differences, and the unadjusted p-value is 0.039. The registry's ANCOVA result is a least-squares mean difference of -11.26 with p = 0.304; confidence limits for that reported result are not reported in the registry record. Since these are different analysis methods, the unadjusted interval should not be used as though it were the interval for the ANCOVA estimate.
The pain-events risk-difference interval runs from -0.396 to 0.109. It includes zero, so the unadjusted result is compatible with both a lower event proportion in the prasugrel group and a higher one under the interval method. The platelet reactivity mean-difference interval runs from -35.85 to -12.26 and excludes zero. The corresponding registry analysis reports p < 0.001.
General statistical explanation: confidence intervals are estimates of precision conditional on the model and method used. They do not account automatically for every source of uncertainty, such as missing data, outcome measurement, or multiple testing. The registry does not report confidence limits for the adjusted secondary estimates. The spread of the unadjusted intervals and the differences in analysis methods should therefore be considered when interpreting the secondary results, rather than relying on a single p-value.
12. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and multiple secondary outcomes, but a multiplicity-adjustment procedure or testing hierarchy is not reported in the registry record. This means it is not possible to determine from the record whether the secondary p-values were intended as confirmatory tests, exploratory analyses, or part of a prespecified sequence. Unadjusted secondary p-values should be read as individual results rather than as a family-wise conclusion about all outcomes.
The primary endpoint defines a safety population as randomized participants who took at least 1 dose of study medication, analyzed according to the treatment they actually received. Its group sizes are 19 for placebo and 41 for 5 mg prasugrel. Secondary group sizes differ across outcomes. The reasons for those differences, the specific analysis population used for each secondary measure, and the method for handling missing observations are not reported in the registry record.
General statistical explanation: missing data may affect estimates when the chance of being observed is related to participant characteristics or outcomes. Complete-case analyses can be difficult to interpret if participants with missing results differ systematically from those with observed results. Imputation or model-based methods can also rely on assumptions. Without the registry's missing-data approach and outcome-specific analysis populations, the possible impact cannot be assessed.
The record identifies ANCOVA for the pain-days analysis and Mixed Models Analysis for platelet reactivity. Their covariates, model specifications, and assumptions are not reported in the registry record. It also does not report interim analyses, stopping rules, or the sample-size justification. Those omissions limit assessment of how the reported analyses relate to the original protocol and whether all planned analyses are represented.
13. 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 |
|---|---|---|---|
| Placebo | 4 | 19 | 21.1% |
| 5 mg Prasugrel | 8 | 41 | 19.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 16 of 19 |
| 5 mg Prasugrel | 33 of 41 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | 5 mg Prasugrel |
|---|---|---|---|
| vascular occlusion | Vascular disorders | 2 of 19 | 2 of 41 |
| sickle cell anaemia with crisis | Congenital, familial and genetic disorders | 1 of 19 | 2 of 41 |
| pain | General disorders | 1 of 19 | 0 of 41 |
| pancytopenia | Blood and lymphatic system disorders | 1 of 19 | 0 of 41 |
| sickle cell anaemia | Congenital, familial and genetic disorders | 0 of 19 | 1 of 41 |
| vertigo | Ear and labyrinth disorders | 0 of 19 | 1 of 41 |
| pneumonia | Infections and infestations | 0 of 19 | 1 of 41 |
| osteonecrosis | Musculoskeletal and connective tissue disorders | 0 of 19 | 1 of 41 |
| thrombosis | Vascular disorders | 1 of 19 | 0 of 41 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | 5 mg Prasugrel |
|---|---|---|---|
| pain | General disorders | 7 of 19 | 11 of 41 |
| headache | Nervous system disorders | 3 of 19 | 5 of 41 |
| vascular occlusion | Vascular disorders | 4 of 19 | 2 of 41 |
| fatigue | General disorders | 2 of 19 | 1 of 41 |
| sickle cell anaemia with crisis | Congenital, familial and genetic disorders | 0 of 19 | 3 of 41 |
| gingival bleeding | Gastrointestinal disorders | 1 of 19 | 2 of 41 |
| nausea | Gastrointestinal disorders | 1 of 19 | 2 of 41 |
| jaundice | Hepatobiliary disorders | 1 of 19 | 2 of 41 |
| nasopharyngitis | Infections and infestations | 1 of 19 | 2 of 41 |
| dizziness | Nervous system disorders | 1 of 19 | 2 of 41 |
Serious events with the highest arm-level rate: vascular occlusion (10.5%), pain (5.3%), pancytopenia (5.3%), sickle cell anaemia with crisis (5.3%), thrombosis (5.3%).
The primary safety result concerns hemorrhagic events requiring medical intervention, with no events recorded in either the placebo group or the 5 mg prasugrel group. Separately, the adverse-event results report serious adverse events affecting 4 of 19 participants in the placebo group and 8 of 41 in the 5 mg prasugrel group. Other adverse events are reported for 16 of 19 and 33 of 41 participants, respectively. These broader adverse-event counts are not the same endpoint as the primary measure of hemorrhagic events requiring intervention.
The serious adverse-event terms listed include vascular occlusion, pain, pancytopenia, sickle cell anaemia with crisis, thrombosis, and sickle cell anaemia, with term-specific percentages reported in the registry. These terms should not be treated as mutually exclusive categories unless the record specifies that they are; that specification is not reported in the registry record. The record does not report deaths in the adverse-event data described.
These counts are descriptive. They do not establish that a particular treatment caused an event or that an event rate differs between groups. The trial was limited to its enrolled participants and follow-up period, and the registry does not provide enough detail to assess event adjudication or comparative safety for outcomes beyond the posted data.
14. What the Result Does, and Does Not, Mean
The primary result means that no hemorrhagic events meeting the registry's medical-intervention definition were observed in either group during the treatment duration. The estimated risk difference is 0.0. This is a report of the trial observations, not proof that the underlying risks are equal, nor proof that such events cannot occur. A finite sample with zero observed events can leave substantial uncertainty about uncommon outcomes.
The secondary results describe other measures, including pain and platelet reactivity. They are not replacements for the primary safety endpoint and should not be used to infer effects on outcomes they do not measure. The pain-days result differs between the unadjusted recalculation and the registry's ANCOVA analysis, underscoring that estimates depend on the analysis method. The platelet reactivity comparison is a laboratory outcome and does not by itself establish a clinical benefit or harm.
General statistical explanation: statistical significance and clinical importance are distinct. A p-value concerns compatibility with a statistical null model; it does not determine whether an observed difference matters to patients. Similarly, a confidence interval describes uncertainty under a method but does not resolve all limitations in design, measurement, or missingness. The trial's duration was 30 days for the primary endpoint, so the posted result addresses that follow-up window rather than longer-term outcomes.
The registry record does not report the full statistical plan, sample-size rationale, multiplicity procedure, or detailed missing-data methods. These gaps restrict how completely the analysis can be evaluated. The results should be read as evidence about the participants and outcomes recorded in this completed trial, without extending them to unmeasured outcomes, other populations, or longer follow-up.
15. Why This Trial Matters Statistically
This trial illustrates an important statistical feature of safety studies: a zero-event result can be clinically relevant to report while remaining limited as a comparative estimate. Both groups had zero recorded primary events, so there is no observed difference in event proportions. Yet the absence of events in this sample cannot demonstrate that the underlying risks are identical or that rare events are impossible. Readers need both the event counts and a careful account of what those counts can establish.
The trial also makes the distinction between an outcome definition and a broader adverse-event listing clear. The primary endpoint required medical attention resulting in therapy or further investigation. Serious and other adverse-event counts describe additional safety information, but they are not interchangeable with that prespecified endpoint. Careful interpretation depends on preserving those distinctions.
For secondary outcomes, the registry includes both unadjusted recalculations and sponsor-reported model-based analyses for some measures. The pain-days example shows that analysis choice can affect the estimate and statistical conclusion. This is why methods, analysis populations, and uncertainty are essential alongside point estimates and p-values. Multiple secondary outcomes also raise the issue of multiplicity; without a reported adjustment or hierarchy, isolated unadjusted findings deserve caution.
Finally, sample-size illustrations based on observed effects are not observed power and do not reveal how the original study was planned. They can help frame future planning under stated assumptions, but the trial's own design rationale is not reported in the registry record. Overall, the record is a useful case for separating observed data, model-based inference, planning scenarios, and limits on what a short follow-up safety comparison can answer.
16. 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.
- Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.
The primary endpoint has no observed events in either group, leaving no observed event contrast for the comparison. The reported point estimate of 0.0 should not be mistaken for precise knowledge that the underlying risks are the same. The primary safety population includes participants who took at least 1 dose and analyzes them according to treatment actually received; the registry does not report the number randomized to each group before this population definition or details of any exclusions.
The follow-up for the primary endpoint is baseline through 30 days. This limits the result to the stated treatment duration; longer-term outcomes are not reported in the registry record. The trial enrolled 62 participants, and the registry does not report the sample-size justification or the intended precision for the primary safety outcome. The stated 7.5 mg dose description is incomplete, while the posted outcome groups identify 5 mg prasugrel and placebo.
Secondary outcome group sizes vary. The reasons for those variations, outcome-specific missing-data handling, and the analysis populations for the secondary outcomes are not reported in the registry record. The registry lists several secondary measures without numerical results for all of them. It also does not report a multiplicity strategy, the covariates and full specifications for the adjusted models, or the interim-analysis plan.
The unadjusted pain-days recalculation and the ANCOVA result are different analyses and yield different estimates and p-values. The platelet reactivity group summaries are reported as least-squares means with standard errors, while the unadjusted comparison uses a recalculation. These distinctions limit direct comparison across summaries. The reported data do not establish causality for individual adverse events, and the record does not provide enough detail to assess all aspects of event classification or analysis conduct.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: Prasugrel Versus Placebo in Adult Sickle Cell Disease — NCT01167023.
- Registry record last updated 2012-05-03; status last verified 2012-04.
- Results first posted 2012-05-03.
- 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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20. Record Summary
This completed phase 2 study randomized 62 adults with sickle cell disease to prasugrel or placebo in a parallel-group, quadruple-masked design. The primary endpoint was hemorrhagic events requiring medical intervention during baseline through 30 days. In the safety population, no such events were recorded among 19 placebo participants or 41 participants receiving 5 mg prasugrel; the risk difference was 0.0.
Posted secondary results cover pain-related outcomes and platelet reactivity, with differing estimates and levels of statistical evidence across outcomes and analysis methods. The registry does not report numerical results for every listed outcome, the multiplicity approach, detailed missing-data methods, or the sample-size rationale. The findings describe the recorded participants and follow-up and should not be taken as proof of equal underlying safety risks or as conclusions about outcomes not measured.