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 Low InTensity Exercise Intervention in PAD (NCT02538900), a randomized na study. The primary outcome is Six-minute Walk Distance.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02538900 |
| Phase | NA |
| Condition | Peripheral Artery Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 305 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Northwestern University |
| Results posted | Yes |
2. Clinical Question
Population
People with peripheral artery disease (PAD). The registry record does not further specify the primary-outcome population.
Intervention
Low-intensity, self-paced walking exercise performed at home.
Comparator
A home-based high-intensity walking program described as ischemic-pain-inducing, and a non-exercising attention control. The control group received staff contact at the same frequency as the exercise groups, with health information unrelated to exercise.
Primary question
Whether change in six-minute walk distance from baseline to week 52 differs with the low-intensity program, including in comparison with the high-intensity program and attention control.
The study is titled “Low InTensity Exercise Intervention in PAD” and is registered as NCT02538900. Its stated rationale focuses on whether a home-based approach that avoids continuous supervision and exercise-related ischemic pain can improve walking performance. The registry summary also describes a secondary aim of comparing high-intensity exercise with attention control on six-minute walk distance.
Other stated secondary aims concern patient-reported outcomes, physical activity, and treadmill walking performance. Those aims broaden the questions beyond the primary walking-distance measure, but their results are not detailed in the primary-outcome figures. The registry record does not report a formal hypothesis, a prespecified contrast hierarchy, or a statistical definition of what would count as a clinically important difference.
3. Trial Design
The registry describes a randomized, single-masked, parallel-group study. Enrollment is listed as 305, and the study status is completed. The registry lists a start date of 2015-06 and primary completion on 2020-10-19. The phase is recorded as NA. The sponsor is Northwestern University.
Participants were assigned to one of three groups. Group 1 received low-intensity, self-paced home walking exercise. Group 2 received standard high-intensity home walking exercise described as ischemic-pain-inducing. Group 3 was a non-exercising attention control. Staff contacted the control group at the same frequency as the exercise groups, but provided health information not related to exercise. This comparator is intended to distinguish the exercise programs from staff contact and attention alone, although the registry record does not report details about how that distinction was incorporated into the analysis.
The registry identifies single masking but does not say which people were masked. It does not report the allocation ratio, eligibility criteria, recruitment settings, or the method used to generate or conceal the random assignment. Nor does it describe the duration or detailed progression of the exercise programs. Those design details are not reported in the registry record.
The primary outcome is six-minute walk distance, measured in meters as change from baseline to week 52. The posted arm estimates are listed for Group 1, Group 2, and Group 3, with group counts of 116, 124, and 65, respectively. The record does not clarify in the primary-outcome entry whether these counts represent all randomized participants, participants with endpoint data, or a defined analysis population.
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 | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| STARTED | 116 | 124 | 65 |
| COMPLETED | 96 | 106 | 48 |
| NOT COMPLETED | 20 | 18 | 17 |
Reasons for not completing this period:
| Reason | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| Death | 2 | 2 | 2 |
| Withdrawal by Subject | 18 | 16 | 15 |
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 | Group 1 | Group 2 | Group 3 | Total |
|---|---|---|---|---|---|
| Participants analysed | 116 | 124 | 65 | 305 | |
| Age, Continuous | years | 69.8 (SD 10.1) | 68.8 (SD 8.7) | 69.5 (SD 10.1) | 69.3 (SD 9.5) |
| Sex: Female, Male: Female | Participants | 54 | 60 | 32 | 146 |
| Sex: Female, Male: Male | Participants | 62 | 64 | 33 | 159 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 4 | 0 | 2 | 6 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 65 | 81 | 35 | 181 |
| Race (NIH/OMB): White | Participants | 45 | 41 | 28 | 114 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 1 | 0 | 3 |
| Region of Enrollment: United States | participants | 116 | 124 | 65 | 305 |
| Ankle-brachial index | ratio | 0.66 (SD 0.17) | 0.67 (SD 0.15) | 0.67 (SD 0.15) | 0.66 (SD 0.16) |
| Body mass index | kg/m^2 | 30.3 (SD 6.7) | 31.1 (SD 7.3) | 30.8 (SD 7.3) | 30.7 (SD 7.1) |
| Six-min walk distance | meters | 326 (SD 99) | 329 (SD 101) | 328 (SD 87) | 328 (SD 97) |
6. Primary Endpoint
The registry lists the primary outcome as Six-minute Walk Distance, measured over change from baseline to week 52.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | meters |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline to week 52 in six-minute walk distance, expressed in meters. The registry describes a standardized test in which participants walk back and forth along a 100-ft hallway for six minutes after receiving instructions to complete as many laps as possible. The recorded distance is the amount covered during that test.
This measure captures walking performance in a timed, standardized task. It is relevant to the trial’s stated question because the interventions are walking programs and the study aims to assess walking performance. Measuring change from baseline places the week-52 result in relation to each participant’s starting measurement, rather than describing only a single follow-up distance.
The posted group values are least-squares means, with 95% confidence intervals. A least-squares mean is a model-based estimate; its exact interpretation depends on the statistical model and any adjustments made. The registry record does not report the model specification or covariates for this endpoint. It also does not provide a direct estimated comparison between groups in the primary-outcome entry, so the group-level values should not be mistaken for estimates of the difference between treatment groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted least-squares mean change is -6.4 meters for Group 1, with a 95% confidence interval from -21.5 to 8.8. For Group 2, the estimate is 34.5 meters, with a 95% confidence interval from 20.1 to 48.9. For Group 3, the estimate is -15.1 meters, with a 95% confidence interval from -35.8 to 5.7. These are changes from baseline to week 52, not week-52 distances.
At the level of these arm estimates, the point estimate for Group 2 is positive, while the point estimates for Group 1 and Group 3 are negative. The confidence intervals for Group 1 and Group 3 include zero; the interval for Group 2 lies above zero. A confidence interval describes uncertainty around an estimate under the analysis used. It is not a range in which every participant’s change falls, nor does it by itself establish the effect of one group relative to another.
The registry record does not provide a two-arm comparison estimate for this continuous endpoint: it indicates that values are missing or not estimable for a two-arm comparison. Consequently, these arm-level estimates do not establish the size or precision of a difference between low-intensity exercise and attention control, between high-intensity exercise and attention control, or between the two exercise groups. A difference between the displayed point estimates would be a new calculation and would not substitute for the trial’s own comparison analysis.
The distinction matters because an intervention effect is ordinarily expressed through a between-group contrast, with uncertainty for that contrast. The uncertainty in a contrast depends on the underlying data and analysis, not simply on reading the separate confidence intervals. The record does not report contrast confidence intervals, p-values, or a decision rule for the primary question. No inferential conclusion about the comparative effect can therefore be drawn from the arm estimates alone.
The posted result is also limited to the six-minute walk endpoint at week 52. Although the registry lists secondary outcomes, the primary-outcome figures do not answer questions about treadmill walking, physical activity, patient-reported outcomes, adherence, muscle biopsy measures, or safety comparisons. Those outcomes require their own results and analysis details.
9. Statistical Methods Explained
What does a least-squares mean represent?
Least-squares means are model-based averages. In general, a statistical model can estimate a group mean while accounting for variables included in that model. The precise meaning of an adjusted mean depends on the model, the covariates, and the population over which the estimate is calculated. The registry record names the result as a least-squares mean but does not report the model formula, covariates, or other details needed to determine what adjustment was made. It is therefore safest to interpret the values as the posted model-based mean changes, without assuming which factors were controlled.
How should the confidence intervals be read?
In general, a confidence interval conveys the precision of an estimate under the statistical method used. A narrower interval indicates more precision than a wider interval, all else being equal. The interval is not a description of the spread of individual participant outcomes. Here, each interval accompanies a group-level mean change in meters. The interval for Group 1 extends from -21.5 to 8.8, the interval for Group 2 from 20.1 to 48.9, and the interval for Group 3 from -35.8 to 5.7.
In general, whether an interval excludes zero can be informative when the estimate is a change or difference for which zero represents no change or no difference. But these are arm-level changes, not the between-group contrasts needed to answer the comparative treatment question. Their intervals should not be used as substitutes for contrast estimates or as a stand-alone test of whether one intervention differs from another. The registry record does not report a p-value for the primary comparison.
Why is the group estimate not the treatment contrast?
A group estimate describes the outcome for one group according to the reported analysis. A treatment contrast directly compares outcomes between groups, such as a difference in mean change. In general, the contrast has its own estimate and uncertainty. It cannot be recovered reliably just by subtracting arm estimates, because the official comparison may depend on the analysis model, covariance structure, adjustments, and participants included. The registry record does not report a usable two-arm comparison for this continuous outcome, so no such contrast is described.
What can the planning illustrations tell a reader?
In general, a sample-size calculation asks how many participants might be needed to detect a chosen effect under stated assumptions. The planning illustrations associated with this study use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They use a stated fraction of the observed effect as the effect to detect. These are planning illustrations based on the observed effect, not the trial’s original design calculations and not observed power. The registry record does not report the trial’s own sample-size justification. Any participant counts in such an illustration should be read as planning quantities per arm, not as counts observed in the trial.
What role does over-dispersion play in general?
Over-dispersion refers, in general, to outcome variability greater than a particular statistical model assumes. If it is present and not accommodated, standard errors can be too small and confidence intervals can be too narrow. This is a general statistical consideration, not a reported feature of this trial. The primary outcome is continuous, and the registry record does not report whether over-dispersion was assessed or how the outcome’s variability was modeled.
What analysis details are absent?
The registry record does not report the primary analysis model, adjustment variables, method for handling missing outcome data, analysis population, or multiplicity procedure. It does not say whether analyses followed a prespecified plan or whether any interim analyses occurred. These omissions limit the ability to assess how the reported arm estimates were produced and how they relate to the study’s planned comparisons. The record lists no analysis results for the direct two-arm comparison of the continuous endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists secondary outcomes that include six-minute walk distance, maximal treadmill walking time, physical activity levels, Walking Impairment Questionnaire distance and speed scores, health-related quality of life, adherence, and muscle biopsy measures. It lists 7 secondary outcomes as posted, but the record does not provide the corresponding analysis details in the outcome information. The stated aims also cover several types of outcomes and comparisons. When researchers examine multiple outcomes or contrasts, the chance of at least one apparently notable result can increase; statistical methods can address that issue, but the registry record does not report a multiplicity adjustment or a hierarchy for testing outcomes.
The record does not report how missing baseline or week-52 measurements were handled, whether imputation was used, or what assumptions were made about missingness. It also does not identify the analysis population for the primary outcome. The group counts accompanying the posted estimates are 116 for Group 1, 124 for Group 2, and 65 for Group 3; the record does not explain whether those counts represent participants with available measurements or another population definition. They should not be treated as a complete account of follow-up or missingness.
The registry record does not report the statistical analysis plan, protocol deviations, or whether the stated outcome analyses were prespecified. These are important for evaluating whether the analysis followed the original plan and how selective reporting may have been limited. Their absence does not show that a particular method was or was not used; it means the relevant information is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Group 1 | 43 | 116 | 37.1% |
| Group 2 | 40 | 124 | 32.3% |
| Group 3 | 19 | 65 | 29.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1 | 2 of 116 |
| Group 2 | 2 of 124 |
| Group 3 | 2 of 65 |
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 |
|---|---|
| Group 1 | 34 of 116 |
| Group 2 | 42 of 124 |
| Group 3 | 29 of 65 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1 | Group 2 | Group 3 |
|---|---|---|---|---|
| Lower extremity revascularization | Cardiac disorders | 8 of 116 | 9 of 124 | 2 of 65 |
| Infection | Infections and infestations | 6 of 116 | 11 of 124 | 1 of 65 |
| Chest pain | General disorders | 5 of 116 | 4 of 124 | 5 of 65 |
| Ischemic heart disease | Cardiac disorders | 4 of 116 | 4 of 124 | 0 of 65 |
| Abdominal problem | General disorders | 3 of 116 | 5 of 124 | 0 of 65 |
| Diabetes | General disorders | 3 of 116 | 2 of 124 | 2 of 65 |
| GI bleed | General disorders | 1 of 116 | 4 of 124 | 2 of 65 |
| Critical limb ischemia | Vascular disorders | 2 of 116 | 4 of 124 | 0 of 65 |
| Fall or fracture | General disorders | 3 of 116 | 1 of 124 | 2 of 65 |
| Pulmonary event | General disorders | 5 of 116 | 0 of 124 | 1 of 65 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1 | Group 2 | Group 3 |
|---|---|---|---|---|
| New or increased dizziness or generalized weakness during activity or exercise | General disorders | 23 of 116 | 21 of 124 | 22 of 65 |
| New or increased shortness of breath during activity or exercise | General disorders | 13 of 116 | 24 of 124 | 19 of 65 |
| New or increased chest discomfort during activity or exercise | General disorders | 9 of 116 | 16 of 124 | 8 of 65 |
Serious events with the highest arm-level rate: infection (8.9%), chest pain (7.7%), lower extremity revascularization (7.3%), pulmonary event (4.3%), abdominal problem (4.0%).
The registry lists serious adverse event affected counts of 43 among 116 at risk in Group 1, 40 among 124 at risk in Group 2, and 19 among 65 at risk in Group 3. It lists deaths as 2 in each group. For other adverse events, the affected counts are 34 among 116 at risk in Group 1, 42 among 124 at risk in Group 2, and 29 among 65 at risk in Group 3. These are group-level counts; the record does not explain whether the affected counts represent participants with at least one event or how repeated events were handled.
The registry also lists serious adverse event terms with percentages: Infection, 8.9%; Chest pain, 7.7%; Lower extremity revascularization, 7.3%; Pulmonary event, 4.3%; Abdominal problem, 4.0%; and Ischemic heart disease, 3.4%. The denominator and the method used to calculate these percentages are not reported in the registry record. They should not be interpreted as group-specific rates.
These figures describe reported safety data, not whether an event was caused by an intervention. The registry record does not provide event timing, severity grading beyond the serious classification, relatedness assessments, or a comparative statistical analysis. Counts and percentages alone do not establish a safety difference between groups.
12. What the Result Does, and Does Not, Mean
The result describes estimated mean change in six-minute walk distance from baseline to week 52 within each group. The posted estimate for the high-intensity group is positive, while the posted estimates for the low-intensity and attention-control groups are negative. The confidence intervals express uncertainty around each arm estimate. This is useful descriptive information about the endpoint, but it is not a direct estimate of the effect of one assigned group compared with another.
The registry record does not report an estimable two-arm comparison for this continuous outcome. Without a between-group estimate and its uncertainty, the arm-level values do not establish how much the groups differed, how precise a difference was, or whether a prespecified primary comparison met a statistical criterion. The displayed mean changes also do not show the range of individual responses or explain which participants contributed to the analysis.
The endpoint is specific: walking distance during a six-minute hallway test at week 52. It does not by itself describe all aspects of mobility, daily activity, symptoms, quality of life, adherence, or safety. The registry lists several secondary outcomes, but their results and analysis methods are not detailed in the primary-outcome entry. Findings on this endpoint should not be taken as answers to those broader questions.
The registry summary gives the study’s rationale and intended comparisons, but it does not report enough methodological detail to reconstruct the analysis. In particular, the model specification, missing-data methods, analysis population, and multiplicity approach are not reported. Those gaps matter when judging the precision and scope of the posted estimates.
Accordingly, the posted data support a description of the reported group mean changes and intervals. They do not, on their own, establish that one exercise approach is superior or inferior, or explain the clinical importance of any between-group difference. No medical conclusion should be drawn from the arm estimates alone.
13. Why This Trial Matters Statistically
This study addresses a design question that is statistically important as well as clinically relevant: how to compare home-based exercise approaches with an attention control while measuring a functional outcome over time. The attention-control group received staff contact at the same frequency as the exercise groups, which is a design feature relevant to separating exercise participation from contact and attention. The record does not report how those factors were handled in the analysis, so the design feature should not be confused with a demonstrated adjustment.
The three-group structure also makes the choice and reporting of comparisons important. The study summary describes questions involving low-intensity exercise, high-intensity exercise, and attention control, while the posted primary outcome gives arm-level estimates without an estimable two-arm comparison. Arm means and confidence intervals can describe each group, but comparative questions require direct contrasts with appropriate uncertainty. Clear reporting of those contrasts, the analysis population, and missing-data handling would allow a more direct assessment of the stated aims.
The endpoint is a standardized six-minute walking task, and the week-52 change places emphasis on performance over follow-up rather than an immediate response. That focus makes transparent reporting of baseline measurement, follow-up availability, and the model for change particularly useful. The registry record names least-squares means but does not report enough detail to assess the model or the endpoint population.
Finally, multiple secondary outcomes and aims make transparent plans for multiplicity and outcome reporting important. The registry record lists 7 secondary outcomes as posted, but does not report a testing hierarchy or adjustment method. These reporting gaps do not invalidate the listed arm estimates; they constrain how confidently the posted information can answer the trial’s comparative questions.
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 main limitation for interpreting the primary result is that the registry record posts arm-level estimates but indicates that a two-arm comparison for the continuous endpoint is missing or not estimable. As a result, the estimates cannot directly answer the comparative question stated for the exercise groups and attention control. The model-based nature of the least-squares means is also difficult to assess because the model specification and adjustment variables are not reported.
The record does not describe the primary-outcome analysis population or explain the group counts attached to the estimates. It does not report how missing measurements were handled, whether participants with incomplete follow-up were included through a particular method, or the assumptions underlying any such method. Therefore the counts should not be read as proof of complete follow-up, and the effect of missing data cannot be evaluated from the registry entry.
Several design details are not reported, including which individuals were masked, the allocation ratio, eligibility criteria, recruitment setting, and the method of random assignment. The record also does not provide detailed intervention schedules or a statistical analysis plan. These gaps limit assessment of implementation, risk of bias, and consistency between planned and reported analyses.
The registry lists secondary outcomes and safety counts but does not give the analysis methods needed to interpret them comparatively. The serious-event percentages are listed without a denominator, and the record does not describe event attribution or timing. These are limitations of the registry record, not evidence that the trial did not collect or analyze such information elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Low InTensity Exercise Intervention in PAD — NCT02538900.
- Registry record last updated 2021-11-16; status last verified 2021-10.
- Results first posted 2021-11-16.
- 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
NCT02538900, “Low InTensity Exercise Intervention in PAD,” is a completed randomized, single-masked, parallel-group study sponsored by Northwestern University. Enrollment is listed as 305. The record lists a start date of 2015-06 and primary completion on 2020-10-19.
The three groups were low-intensity self-paced home walking, high-intensity home walking described as ischemic-pain-inducing, and a non-exercising attention control with staff contact at the same frequency. The primary outcome is change from baseline to week 52 in six-minute walk distance, reported as least-squares mean changes with 95% confidence intervals.
The registry does not provide an estimable two-arm comparison for this continuous endpoint. It also does not report the primary analysis model, missing-data approach, analysis population, or multiplicity method. The posted arm estimates are therefore descriptive of the listed group results and do not by themselves establish a between-group effect.