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 Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment (NCT03329599), a randomized phase 2 study. The primary outcome is Carotid Intimal Media Thickness.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03329599 |
| Phase | Phase 2 |
| Condition | Atherosclerosis, Adherence, Medication, Tolerance |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 148 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Northern California Institute of Research and Education |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned Ghanaian first-time stroke survivors, described in the brief summary as recent ischemic stroke survivors. Atherosclerosis, medication adherence, and tolerance are listed among the conditions. The registry record does not give a more detailed primary-outcome population definition.
Intervention
The polypill arm was assigned a hard capsule taken orally once daily. It contained 2/3 antihypertensives, a moderate/high-intensity statin, and Aspirin. The record names Polycap as the intervention.
Comparator
The usual-care arm continued separate, individual secondary preventive medications as prescribed. The record does not specify the exact medicines used by each participant in this arm.
Primary question
The central comparison was whether the polypill strategy, compared with usual care, was associated with carotid intimal media thickness at baseline and 12 months. The brief summary also identifies adherence and tolerability as objectives. The posted primary estimates are arm-specific means with 95% confidence intervals; a direct between-arm estimate or test is not reported in the registry record.
3. Trial Design
SMAART is a Phase 2, randomized, parallel-group clinical trial. The registry records quadruple masking, but does not describe which people or roles were masked. It lists an enrollment of 148. The brief summary separately states that the study planned to recruit 120 recent ischemic stroke survivors and randomize them 1:1. The record does not explain the difference between the planned recruitment figure and the enrollment figure.
The study compares a polypill regimen with usual care. The polypill is described as a once-daily oral capsule containing 2/3 antihypertensives, a moderate/high-intensity statin, and Aspirin. Usual care consists of separate individual secondary preventive medications as prescribed. The record does not specify the exact usual-care regimens or how medication choices were made.
The listed start date is 2019-02-14, the primary completion date is 2021-12-01, and the status is completed. The sponsor is Northern California Institute of Research and Education. The brief summary frames the study as an assessment of carotid intimal thickness, adherence, and tolerability, with the broader objective of informing a future multicenter trial in the African context. That future objective is a rationale, not a result of the current trial.
Although randomization and masking are recorded, details of the randomization procedure, allocation concealment, and masking roles are not reported in the registry record. The reported endpoint estimates can therefore be described, but the record does not support a fuller account of how assignment or masking was implemented.
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 | Polypill | Usual Care |
|---|---|---|
| STARTED | 74 | 74 |
| COMPLETED | 59 | 64 |
| NOT COMPLETED | 15 | 10 |
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 | Polypill | Usual Care | Total |
|---|---|---|---|---|
| Participants analysed | 74 | 74 | 148 | |
| Age, Continuous | years | 58.5 (SD 10.7) | 58.1 (SD 13.3) | 58.3 (SD 12.07) |
| Sex: Female, Male: Female | Participants | 38 | 36 | 74 |
| Sex: Female, Male: Male | Participants | 36 | 38 | 74 |
| 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 | 74 | 74 | 148 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 |
| 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: Ghana | Participants | 74 | 74 | 148 |
| Educational Status: None | Participants | 11 | 15 | 26 |
| Educational Status: Primary | Participants | 42 | 28 | 70 |
| Educational Status: Secondary | Participants | 12 | 18 | 30 |
| Educational Status: Tertiary | Participants | 9 | 12 | 21 |
| Educational Status: Postgraduate | Participants | 0 | 1 | 1 |
| Urban Residence | Participants | 42 | 37 | 79 |
| Marital Status: Never married | Participants | 6 | 5 | 11 |
| Marital Status: Married | Participants | 43 | 47 | 90 |
| Marital Status: Separated | Participants | 12 | 5 | 17 |
| Marital Status: Widow or widower | Participants | 11 | 14 | 25 |
| Marital Status: Cohabiting | Participants | 0 | 1 | 1 |
| Marital Status: Divorced | Participants | 2 | 2 | 4 |
| Employment Status: Employed | Participants | 54 | 45 | 99 |
| Employment Status: Retired | Participants | 11 | 10 | 21 |
| Employment Status: Unemployed | Participants | 9 | 19 | 28 |
| Monthly Income: 0-100, US $ | Participants | 7 | 11 | 18 |
| Monthly Income: 101-250 | Participants | 37 | 37 | 74 |
| Monthly Income: 250-500 | Participants | 27 | 24 | 51 |
| Monthly Income: >500 | Participants | 3 | 2 | 5 |
| Hypertension | Participants | 74 | 74 | 148 |
| Haemoglobin A % | percent | 6.5 (SD 1.7) | 7 (SD 2.5) | 6.75 (SD 2.14) |
| BMI | kg/m^2 | 25.4 (SD 4.3) | 25.7 (SD 5.1) | 25.55 (SD 4.72) |
| Waist-to-hip Ratio | cm | 92.2 (SD 10.3) | 90.6 (SD 12.1) | 91.4 (SD 11.24) |
| Stroke subtype: Small vessel disease | Participants | 11 | 23 | 34 |
| Stroke subtype: Large vessel disease | Participants | 20 | 16 | 36 |
| Stroke subtype: Undetermined | Participants | 43 | 35 | 78 |
6. Primary Endpoint
The registry lists the primary outcome as Carotid Intimal Media Thickness, measured over Baseline and 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | mm |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is carotid intimal media thickness, measured in millimeters. It refers to the thickness of the intima and media layers of the carotid arteries. The stated timeframe is baseline and 12 months. These layers provide a structural measure related to atherosclerosis, and the brief summary describes carotid intimal thickness as a surrogate marker of atherosclerosis.
A surrogate endpoint is a measured feature used to assess a process of interest rather than a direct measure of a clinical event. Such measures can be useful in research, but an estimate for a surrogate does not by itself establish an effect on clinical outcomes. The registry record describes a mean and a 95% confidence interval for each arm. It does not specify whether the posted means represent endpoint values, changes from baseline, or another summary, so their exact calculation cannot be determined from the record.
The result should therefore be read as the posted mean estimate for each arm, with its stated uncertainty, rather than as a reported direct treatment contrast. The registry record does not provide a between-arm estimate for the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results are arm-specific mean estimates. For Polypill, the mean is -0.017 mm, with a 95% confidence interval from -0.067 to 0.034. For Usual Care, the mean is -0.092 mm, with a 95% confidence interval from -0.13 to -0.051. The corresponding arm counts listed with these estimates are 59.0 and 64.0. The registry gives the endpoint timeframe as baseline and 12 months.
The intervals describe uncertainty around each reported arm mean, not uncertainty around a direct comparison of the arms. The Polypill interval contains values on both sides of zero; the Usual Care interval is entirely below zero. Those observations do not establish whether the arms differ. A direct between-arm estimate, its confidence interval, and a test result are not reported in the registry record. The record also does not clarify whether these mean estimates are changes, follow-up values, or another endpoint summary.
The distinction between within-arm descriptions and a randomized comparison is important. A mean in each arm describes that arm’s reported result. The treatment question concerns the contrast between assigned strategies. Without a reported contrast or a stated analysis that estimates it, the arm-specific numbers alone do not quantify the size or precision of the between-arm effect.
Seven secondary outcomes are listed: Morisky Adherence Scale Score, Hill-Bone Score, EQ-5D Quality-of-Life Score, Treatment Satisfaction Questionnaire for Medication Score, Montreal Cognitive Assessment Score, Modified Rankin Score, and Hamilton Rating Scale for Depression Score. The registry records eight outcome measures in total, but the posted results summarized for this analysis do not include estimates for those secondary outcomes. The record reports zero analyses. It therefore does not provide a basis for interpreting secondary outcome effects or for comparing their results with the primary endpoint.
Safety counts are also recorded for each arm, including serious adverse events, other adverse events, and deaths. They are counts, and the record does not provide a formal comparative safety analysis. These figures should not be treated as evidence of a causal difference in safety between the assigned strategies.
Overall, the registry provides descriptive arm-level primary estimates and safety counts, but not the direct comparative analysis needed to quantify the primary treatment contrast. The estimates can be read as posted, with attention to their confidence intervals and to the limits of the information recorded.
9. Statistical Methods Explained
The primary endpoint is continuous, and the registry identifies the reported quantity as a mean with a 95% confidence interval. These features determine how the posted estimates should be read, while leaving important aspects of the analysis uncertain.
What does a mean represent?
In general, a mean is a measure of the center of a set of numerical observations. For a continuous endpoint such as carotid intimal media thickness, it summarizes the measurements on the endpoint’s scale. A mean does not describe every participant’s result, nor does it show the spread of individual measurements. The registry lists no dispersion measure beyond the confidence interval for the mean. The record does not report the underlying participant-level observations or explain how any missing measurements were handled.
The reported Polypill mean is -0.017 mm, and the reported Usual Care mean is -0.092 mm. The registry gives 95% confidence intervals of -0.067 to 0.034 for Polypill and -0.13 to -0.051 for Usual Care. Because the description does not say whether these values are endpoint measurements, changes, or another summary, interpretation should remain tied to the values and labels actually recorded.
What does a confidence interval communicate?
In general, a confidence interval expresses uncertainty around an estimate under the method used to construct it. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. A 95% confidence interval is not a range that guarantees the true value lies inside it. Its interpretation depends on the statistical procedure and assumptions used to calculate it. The procedure for these intervals is not reported in the registry record.
The intervals are attached to each arm’s estimate. They are not a confidence interval for the difference between the assigned strategies. A direct comparison typically requires an estimated contrast and its uncertainty, taking account of the trial design and analysis. Neither a primary between-arm estimate nor a primary p-value is reported in the registry record. The arm intervals should not be substituted for those missing comparative results.
Why does the analysis population matter?
Random assignment defines the groups to which participants were assigned, but a report also needs to state which participants contributed to each analysis and how the analysis treated departures from the assigned regimen or unavailable measurements. The record lists arm counts alongside the endpoint estimates, but does not define the analysis populations or explain whether all randomized participants were included. The handling of adherence, withdrawals, and missing endpoint measurements is not reported in the registry record.
In general, missing outcome data can affect both the precision and the interpretation of an estimate. The consequences depend on why data are missing and on the analytic approach. Without information about the amount, pattern, and handling of missingness, the robustness of the posted means cannot be assessed from the registry record alone.
What can be said about planning calculations?
Planning illustrations based on an observed effect are hypothetical sample-size calculations, not observed power and not trial results. The stated assumptions for such illustrations are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For continuous outcomes, the illustrations are expressed as participants per arm. These assumptions describe planning calculations and should not be mistaken for the trial’s original design justification. The registry record does not report the trial’s sample-size justification or a statistical power analysis for the completed study.
More generally, sample-size calculations rely on assumptions about the effect to detect, variability, significance level, and design. Changing those assumptions changes the planning result. An illustration based on the observed estimate is especially different from evidence that the completed trial had a particular probability of detecting an effect. It is not a substitute for a prespecified design calculation or for a reported test of the primary comparison.
What is not specified?
The registry records randomization, quadruple masking, a parallel model, and the primary endpoint summary. It does not report the randomization sequence method, the identities of masked roles, the primary statistical model, covariate adjustment, the precise endpoint derivation, or a testing procedure for the primary contrast. The record also reports zero analyses. These omissions mean that a reader cannot reconstruct the planned or completed inferential analysis from the registry entry. General statistical explanations can clarify the meaning of means and confidence intervals, but cannot fill in those missing trial-specific details.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven secondary outcomes in addition to the primary carotid intimal media thickness endpoint, and records eight outcome measures overall. The secondary measures cover adherence, quality of life, treatment satisfaction, cognition, functional status, and depression. No secondary outcome results are included in the posted results, and the registry records zero analyses.
When a study assesses multiple outcomes, the chance of at least one apparently notable finding can increase if each outcome is tested separately without an appropriate plan. In general, multiplicity methods can address this issue, but the suitable approach depends on the study’s objectives and prespecified analysis. Whether the trial used an adjustment, a hierarchy, or another strategy for multiple outcomes is not reported in the registry record. No claims about secondary outcome significance or multiplicity-adjusted inference can therefore be made from this record.
The record does not describe the analysis populations for the primary or secondary endpoints. It does not report how many endpoint observations were unavailable, why any were missing, or whether any imputation or sensitivity analysis was used. The handling of withdrawals, protocol deviations, and treatment discontinuation is also not reported in the registry record. These details matter because the analyzed participants and the treatment of missing outcomes can affect both the estimate and its uncertainty.
The listed arm counts accompanying the primary estimates do not, by themselves, establish which analysis population was used or how those counts relate to random assignment. The registry enrollment figure and the planned recruitment figure in the brief summary are not the same, and the record does not explain that difference. As a result, the available information supports a description of the posted values, but not a full assessment of completeness, analysis-set selection, or multiplicity control.
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 |
|---|---|---|---|
| Polypill | 3 | 74 | 4.1% |
| Usual Care | 0 | 74 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Polypill | 5 of 74 |
| Usual Care | 2 of 74 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Polypill | 5 of 74 |
| Usual Care | 7 of 74 |
Most frequent serious adverse event terms
| Event term | Organ system | Polypill | Usual Care |
|---|---|---|---|
| Post-stroke seizures | Vascular disorders | 2 of 74 | 0 of 74 |
| Hospitalization | Surgical and medical procedures | 1 of 74 | 0 of 74 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Polypill | Usual Care |
|---|---|---|---|
| Regimen Adjustments | Vascular disorders | 5 of 74 | 7 of 74 |
| Treatment Discontinuation | Vascular disorders | 3 of 74 | 0 of 74 |
| Cough | Respiratory, thoracic and mediastinal disorders | 3 of 74 | 0 of 74 |
| Gatrointestinal Bleeding | Gastrointestinal disorders | 1 of 74 | 0 of 74 |
Serious events with the highest arm-level rate: post-stroke seizures (2.7%), hospitalization (1.4%).
The registry records serious adverse events for 3 participants in the Polypill group and 0 in the Usual Care group. The serious-event at-risk counts are 74 for each group. It lists other adverse events affecting 5 participants in Polypill and 7 in Usual Care, with other-event at-risk counts of 74 in each group. Death counts are 5 for Polypill and 2 for Usual Care. These are posted counts; no comparative estimate or uncertainty interval for safety is reported in the registry record.
The listed top serious adverse event terms are Post-stroke seizures at 2.7% and Hospitalization at 1.4%. The registry record does not state how those term percentages were calculated or whether event terms could overlap. It also does not report causes of death or whether deaths were judged related to treatment.
Counts should not be interpreted as proof that one strategy caused more or fewer events. The record does not provide a formal safety analysis, event timing, exposure duration, or adjudication details. The figures describe what was recorded, but the limited information does not support a complete comparison of safety between the groups.
12. What the Result Does, and Does Not, Mean
The result establishes what the registry record reports: arm-specific mean estimates for carotid intimal media thickness, with 95% confidence intervals, at a stated baseline and 12-month timeframe. It also records safety counts. These data offer a descriptive account of the posted outcomes, but they do not supply a direct estimate of the randomized comparison for the primary endpoint.
A randomized trial’s main comparative question is about the difference attributable to assignment, interpreted with uncertainty and in light of the analysis plan. Here, the registry gives a mean and interval for each arm, but not the estimated contrast, its interval, or a test result. It also does not clarify whether the means represent changes from baseline or another summary. Thus, the numerical arm estimates should not be converted into an unreported treatment effect.
The endpoint is a surrogate measure related to atherosclerosis, as described in the brief summary. Even a clear result for a surrogate would not, by itself, establish an effect on clinical events. The registry record does not report results for the listed secondary outcomes, nor does it provide the missing analytic details needed to assess multiplicity, missing data, or the precise analysis population.
The safety figures are similarly descriptive. They include event and death counts, but the record does not give a formal comparative safety analysis or details about event attribution. The counts alone do not establish that the assigned strategies caused different safety outcomes.
Accordingly, the available record supports a careful reading of the posted estimates and their stated precision, while leaving the treatment contrast and several important analysis questions unresolved. It does not justify a broader conclusion about clinical efficacy, clinical outcomes, adherence, or tolerability beyond results actually reported in the registry.
13. Why This Trial Matters Statistically
This trial is statistically notable because its registry record combines randomized design information with arm-specific endpoint summaries but does not report the direct comparison that answers the primary treatment question. Distinguishing descriptive estimates from comparative inference is essential: a mean for each arm is not itself an estimate of the difference between assigned strategies.
The endpoint is a continuous surrogate measure, and the record reports means with 95% confidence intervals. This makes precision visible at the arm level, but not for the randomized contrast. In general, confidence intervals help readers assess uncertainty, yet their interpretation depends on the estimator and procedure. Those analytic details are not reported in the registry record.
The record also illustrates why outcome planning and transparent reporting matter. Seven secondary outcomes are listed, but their results are not reported in the posted results, and the registry records zero analyses. Without a stated multiplicity strategy, analysis population, or approach to missing measurements, readers cannot fully evaluate how the reported summaries relate to the complete study plan.
Finally, the distinction between the enrollment figure and the planned recruitment figure is unresolved in the record. Reporting the reason for that difference, along with the statistical analysis plan and complete endpoint results, would help readers understand the evidence more fully. These are reporting questions rather than conclusions about the conduct or validity of the trial. The current entry supports measured interpretation, not a stronger claim than the recorded comparative evidence allows.
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 of interpretation arise from what is not reported in the registry record. The primary endpoint is described as carotid intimal media thickness at baseline and 12 months, but the record does not state whether the arm means are follow-up measurements, changes from baseline, or another summary. The direct between-arm estimate, its uncertainty, and the test result are not reported. This prevents a reader from quantifying the primary randomized contrast based on the registry entry alone.
The analysis method is also not described. The record does not report the statistical model, any covariate adjustment, or the method used to construct the confidence intervals. It does not state the analysis population, how missing endpoint measurements were handled, or whether sensitivity analyses were conducted. Randomization and quadruple masking are listed, but implementation details and masked roles are not reported.
The enrollment figure is 148, while the brief summary says the study planned to recruit 120. The record does not explain the difference. It also does not provide primary analysis results for the seven listed secondary outcomes, or a multiplicity strategy for interpreting multiple endpoints. Although safety counts are listed, details about event timing, attribution, and comparative analysis are not reported.
These gaps do not establish that a particular method was or was not used; they limit what can be concluded from the registry record. The posted estimates remain useful descriptive information, but a complete assessment of the trial’s primary inference, missing data, and safety comparison requires details not reported in the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment — NCT03329599.
- Registry record last updated 2023-12-20; status last verified 2023-12.
- Results first posted 2023-12-20.
- 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
SMAART is a completed Phase 2 randomized, quadruple-masked, parallel-group trial sponsored by Northern California Institute of Research and Education. The registry lists enrollment of 148 and gives a planned recruitment figure of 120 in the brief summary; the difference is not explained. The listed start date is 2019-02-14 and the primary completion date is 2021-12-01.
The trial compares a once-daily polypill with usual care among Ghanaian first-time stroke survivors. Its primary endpoint is carotid intimal media thickness, with baseline and 12 months listed as the timeframe. The posted arm means have 95% confidence intervals, but a direct between-arm primary estimate and the details of its analysis are not reported in the registry record. Seven secondary outcomes are listed, while their results are not reported in the posted results. Safety event and death counts are recorded without a formal comparative safety analysis.