Pivotal Study of a Percutaneous Mitral Valve Repair System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pivotal Study of a Percutaneous Mitral Valve Repair System (NCT00209274), a randomized na study. The primary outcome is Number of Participants With Major Adverse Events (MAE).

2. Clinical Question

The primary endpoint is a count of participants who experienced at least one event in the specified composite. The posted comparison is unadjusted, and the registry record describes the analysis population as per-protocol, with available follow-up data at that time frame. This question is distinct from asking whether either procedure is preferable for an individual; the registry comparison describes outcomes in the analyzed trial groups and does not establish an individual-level conclusion.

3. Trial Design

The registry describes EVEREST II as a prospective, multi-center, randomized study comparing percutaneous mitral valve repair using the MitraClip implant with mitral valve repair or replacement surgery. The listed allocation is randomized, the study model is parallel, and masking is listed as none. The registry lists enrollment as 279 and status as completed. It gives a study start of 2005-08 and primary completion of 2009-11. The phase is listed as NA.

The registry's arm descriptions give calculated sample sizes of 186 patients for the device arm and 93 for the control arm. These are the arm sizes described in the registry record, not the denominators used in the primary outcome comparison. For that outcome, the posted per-protocol analysis includes 136.0 participants in the device group and 79.0 in the surgery group. The record does not explain the difference between the planned arm sizes and the analyzed denominators in detail.

The primary endpoint is assessed at 30 days. The registry summary describes clinical and echocardiographic follow-up at 30 days, 6 months, 12 months, 18 months, and 24 months, followed by annual follow-up for 5 years. The record also describes a separate high surgical risk registry and a continued-access study, but those are not the randomized comparison analyzed by the primary result.

The original randomization procedures, allocation concealment, eligibility criteria, site-level methods, adherence rules, and the trial's original statistical design assumptions are not reported in the registry record. The registry identifies the sponsor as Abbott Medical Devices.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: The EVEREST II RCT enrolled 279 patients (184 Device and 95 Control), of whom 21 patients (6 Device and 15 Control) did not undergo treatment per their randomized assignment, and are reported as "randomized not treated" (RNT). All RNT patients except one withdrew from the trial.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-protocol cohort. The number of participants analyzed includes subjects who had available follow up data at that time frame.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Major Adverse Events (MAE), measured over 30 days.

The primary endpoint is the number of participants with major adverse events at 30 days. It is a composite: a participant qualifies if one or more of the listed events occurred. The components include death, myocardial infarction, reoperation for failed surgical repair or replacement, nonelective cardiovascular surgery for adverse events, stroke, renal failure, deep wound infection, ventilation for more than 48 hours, a gastrointestinal complication requiring surgery, new onset of permanent atrial fibrillation, septicemia, or transfusion of 2 or more units of blood.

A composite endpoint can capture several clinically important types of harm in one summary and may register more events than a single component would. Its interpretation depends on the components: the overall count does not show which event drove the group comparison, whether events differed in severity, or whether one component outweighed another. Component-specific primary endpoint results are not reported in the registry record.

The posted endpoint is a participant count, not a count of all event episodes. The population is described as per-protocol, and the number analyzed includes participants with available follow-up at that time. Consequently, the reported comparison concerns the analyzed participants and the combined endpoint as defined in the record; it does not by itself describe every possible outcome or the distribution of individual components.

7. Results Posted in the Registry

• Device Group (MitraClip Device): 9.6% (13/136) versus 57.0% (45/79) on control; risk difference -47.4 percentage points (95% CI -59.4 to -35.4), risk ratio 0.17 (0.10–0.29); unadjusted two-proportion z-test p = <0.001.

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.

Freedom From All-Cause Mortality

• 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:
  • Device Group (MitraClip Device): 93.7% (148/158) versus 92.9% (65/70) on control; risk difference 0.8 percentage points (95% CI -6.3 to 7.9), risk ratio 1.01 (0.93–1.09); unadjusted two-proportion z-test p = 0.819.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Device Group (MitraClip Device) and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation.

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Device Group (MitraClip Device): 67.4% (118/175) versus 73.0% (65/89) on control; risk difference -5.6 percentage points (95% CI -17.1 to 5.9), risk ratio 0.92 (0.78–1.09); unadjusted two-proportion z-test p = 0.351.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Device Group (MitraClip Device) and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation (MR).

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Device Group (MitraClip Device): 69.0% (87/126) versus 80.9% (55/68) on control; risk difference -11.8 percentage points (95% CI -24.2 to 0.5), risk ratio 0.85 (0.72–1.01); unadjusted two-proportion z-test p = 0.076.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Device Group (MitraClip Device) and the control. The interval gives the range of effects that remain compatible with the data.

The selected secondary outcomes do not show one uniform pattern. The mortality comparison at 12 months has a point estimate close to no difference, while the valve-related freedom outcomes have point estimates on the side of a lower proportion in the device group. The confidence intervals for these selected comparisons include no difference, so their estimates remain uncertain. This contrasts with the primary composite comparison, whose interval lies below zero, but the endpoints describe different outcomes and timeframes and should not be treated as interchangeable measures.

The secondary findings neither overturn nor independently confirm the primary result. Mortality is one component of the primary composite, but the 12-month mortality outcome is a distinct measure at a later time. The valve-related outcomes combine freedom from surgery for valve dysfunction, death, and moderate to severe or severe mitral regurgitation. Their definitions differ from the 30-day composite of adverse events. A difference in one endpoint therefore need not imply a matching difference in another.

The registry lists 157 outcome measures and 155 posted secondary outcomes, while the selected comparisons are only a subset of the outcome record. The registry does not report a hierarchy establishing which secondary outcomes were confirmatory, nor does it report a multiplicity adjustment. General explanation: when many outcomes are tested, an isolated unadjusted result is more vulnerable to chance findings. For that reason, secondary estimates should be read as supportive descriptive evidence with their uncertainty, not as a collection of independent definitive tests.

The registry record also does not supply reported analyses for these selected secondary outcomes. The posted unadjusted comparisons can describe the available group data, but the absence of a reported analysis plan makes it difficult to assess prespecification, analytic choices, and the role these results were intended to play. No clinical conclusion should rest on a single secondary p-value without considering those limitations and the confidence interval.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Freedom From All-Cause Mortality
• Freedom From All-Cause Mortality
• Freedom From All-Cause Mortality
• Freedom From All-Cause Mortality
• Freedom From All-Cause Mortality
• Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation.
• Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation (MR).
• Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation (MR) in Intention to Treat Strategy Cohort

9. Statistical Interpretation

10. Statistical Methods Explained

These comparisons concern binary outcomes: each analyzed participant either meets the outcome definition or does not. For the primary endpoint, the outcome is having a major adverse event within the 30-day timeframe. The registry gives the number with the event and the number analyzed in each group. This makes the group counts interpretable, but the denominators are specific to the stated per-protocol population and available follow-up.

What does the risk difference express?

The risk difference subtracts the comparator group's event proportion from the device group's event proportion. A negative value therefore indicates a lower observed event proportion in the device group for an outcome defined as having the event. The primary estimate is -0.474. The confidence interval for this estimate lies below zero, and the unadjusted p-value is < 0.001. These are unadjusted comparisons; they do not account for possible confounding factors through a model, and no adjusted analysis is reported in the registry record.

For a secondary outcome defined as freedom from an event, the direction needs careful reading. A positive risk difference would mean a higher observed proportion meeting the freedom definition in the device group; a negative one means a lower proportion. The sign is always interpreted in relation to the outcome as defined, not as a generic measure of benefit or harm. Risk differences are absolute contrasts on the probability scale, whereas a ratio compares proportions relative to one another. The posted secondary comparisons include risk differences, and the record also contains recalculated relative measures; those do not replace the outcome definition or analysis-population context.

How should a p-value be read?

General explanation: a p-value describes how incompatible the observed data, or data more extreme, are with a specified null model of no group difference. A small p-value is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. A p-value also does not address bias, missing data, endpoint selection, or whether the model's assumptions are appropriate. The p-values in these comparisons are unadjusted, so they do not account for testing many outcomes.

The primary unadjusted p-value is < 0.001. For the selected secondary comparisons, the posted unadjusted p-values are 0.819, 0.351, and 0.076. These should be considered alongside effect estimates and confidence intervals. In particular, a value that does not meet a conventional threshold does not prove that groups are identical; it may reflect imprecision, a small difference, or both. The registry record does not state a threshold or multiplicity strategy for the trial's original analyses.

What does the confidence interval add?

General explanation: a confidence interval describes a range of estimates compatible with the data under the method used. Its width conveys statistical precision: wider intervals allow a broader range of underlying group differences, while narrower intervals constrain that range more closely. An interval crossing zero for a risk difference includes no difference among the values compatible with the method; an interval entirely on one side of zero indicates that the method's interval does not include no difference. This is not a guarantee about the true effect and does not correct for design limitations or multiple comparisons.

For the primary comparison, the interval is entirely below zero. For each selected secondary comparison, the interval includes zero. The exact endpoints are not repeated in this explanation; the posted comparison values remain the reference for their reported precision. The primary result is more statistically separated from zero than the selected secondary results, but its interpretation still depends on the composite endpoint and the per-protocol analysis population.

Why do the analysis population and denominator matter?

The registry identifies the primary population as per-protocol and says that the analyzed count includes participants with available follow-up at the relevant time. A per-protocol analysis generally concerns participants who met specified adherence or protocol criteria, but the exact criteria are not reported in the registry record. It is therefore not possible to establish from this record alone which participants were excluded or why. Nor does the available-follow-up statement explain whether missing outcomes were imputed, treated as failures, or handled in another way.

The denominators vary across the posted outcomes and timeframes. That can occur when the outcome population or follow-up availability differs, but the record does not give enough detail to attribute the variation to a particular cause. Counts from different timepoints should not be treated as if they came from an identical analysis set. The parallel randomized design is relevant to interpreting group comparisons, but randomization alone does not resolve consequences of post-randomization exclusions or missing observations.

What limits the secondary analyses?

The registry record lists many outcome measures, but no multiplicity adjustment or hierarchy for these secondary outcomes is reported. General explanation: as the number of statistical tests increases, the chance of at least one apparently notable result arising by chance also increases. A p-value from one unadjusted secondary comparison therefore carries less evidential weight when many outcomes may have been examined. The registry contains no reported analyses for the selected secondary result entries, so the comparisons should not be mistaken for a fully described sponsor analysis. Their estimates and p-values are useful descriptions of the posted data, but the record does not establish their prespecified status or confirmatory role.

11. Confidence Intervals and Precision

Precision is most directly conveyed by the confidence intervals around the group contrasts. For the primary 30-day major adverse event comparison, the interval lies entirely below zero. The estimated risk difference is -0.474, with an unadjusted p-value of < 0.001. This indicates that the posted estimate is separated from no difference under the method used. It does not eliminate concerns about the analysis population, missing follow-up, or the combined nature of the endpoint.

The selected secondary intervals are wider in relation to their point estimates and include zero. At 12 months, the mortality comparison is compatible with no group difference as well as differences in either direction. The 12-month valve-related freedom outcome is similarly uncertain, and the 24-month result also has an interval that includes zero. The point estimate alone should not be treated as a precise description of the underlying group contrast when the interval spans a range that includes no difference.

General explanation: a confidence interval is not a range containing a fixed share of individual participant outcomes. It is an interval produced by a statistical method, intended to reflect uncertainty in an estimated group contrast under that method's assumptions. It does not account automatically for selective outcome reporting, unmeasured sources of bias, or testing many outcomes. Those considerations are especially relevant for secondary comparisons without a reported multiplicity approach.

The precision also depends on how many participants contribute to each analysis and how often the outcome occurs. The registry denominators differ across outcomes, so precision cannot be compared solely by looking at point estimates. The available record does not report a formal precision target or original sample-size rationale for these outcomes. Accordingly, confidence intervals help describe the statistical uncertainty in the posted contrasts, but they do not settle the broader clinical or design questions.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrative calculations based on the observed effect, not a record of the trial's original sample-size rationale. For these binary outcomes, the listed figures are participants per arm. The sample-size method assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It sets the effect to detect at the stated fraction of the observed effect. The record's note about total event counts using the Schoenfeld method applies to time-to-event outcomes; these listed binary-outcome planning values are participants per arm.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and the assumptions hold. The 90% power column gives the corresponding number for a higher chance of detection. For example, planning for 100% of the observed primary effect gives 15 participants per arm for 80% power and 19 participants per arm for 90% power. Planning for 75% of the observed effect gives 29 participants per arm for 80% power and 38 participants per arm for 90% power; planning for 50% gives 69 and 91 participants per arm, respectively.

Smaller effects are harder to distinguish from random variation, so the illustrative calculations require more participants as the target effect becomes smaller. These values are not observed power: they are planning illustrations, and they do not show the probability that the completed trial detected its true effect. The trial's own original sample-size assumptions and justification are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.570; treatment proportion p₁ = 0.096; average p̄ = 0.333.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6663 = 1.3059.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5759 = 0.4846.
4. n = (1.3059 + 0.4846)² / (-0.4740)² = 14.3, rounded up to 15 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.569620253164557                          # control proportion
p1 <- 0.0955882352941176                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(209274)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 15 (80% power), 19 (90% power)
 75% of observed effect: n per arm = 29 (80% power), 38 (90% power)
 50% of observed effect: n per arm = 69 (80% power), 91 (90% power)
power.prop.test: 14.3 
Simulated power at n = 15 per arm: 0.851 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity, missing data, and analysis population are important interpretive issues in this record. The registry lists 157 outcome measures and 155 posted secondary outcomes. It does not report whether the investigators used a formal multiplicity correction, a gatekeeping procedure, or a prespecified hierarchy for interpreting the outcomes. Without such information, the selected unadjusted secondary p-values should be treated cautiously; testing many outcomes can make chance findings more likely.

The primary endpoint population is described as per-protocol, and the analyzed number includes participants with available follow-up at that timeframe. The record does not report the exact per-protocol criteria, the number excluded from that population, reasons for exclusions, or how missing endpoint observations were handled. It also does not report whether missingness differed by group or whether sensitivity analyses were conducted. These omissions limit assessment of how closely the analyzed groups preserve the benefits of random allocation.

Randomized allocation is a design strength for comparing assigned groups, but a per-protocol analysis may not retain all participants as randomized. The record does not provide enough information to reconstruct an intention-to-treat analysis for the primary endpoint. Some secondary outcome titles refer to an intention-to-treat strategy cohort, but the available record does not establish that all posted outcomes use the same analysis population or explain how that strategy was implemented.

Denominators differ across outcomes and follow-up times. This makes it important to interpret each estimate using its own analyzed group sizes rather than assuming a common population throughout. The registry summary describes planned follow-up through 24 months and annually for 5 years, but it does not provide a complete account of follow-up completeness or missing-data methods for the posted comparisons. The trial's original statistical analysis plan, including interim analyses and handling of multiplicity, is not reported in the registry record.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial arrhythmia (16.9%), other (12.9%), congestive heart failure (12.5%), residual/recurrent mitral regurgitation (mr) (11.8%), death (11.2%).

The safety record reports serious adverse events for 127 of 178 participants at risk in the device group and 54 of 80 at risk in the surgery group. It reports other adverse events for 168 of 178 and 80 of 80, respectively. These are group-level adverse event summaries, separate from the per-protocol primary endpoint counts. The registry does not define in this record how the adverse-event risk populations relate to the primary analysis populations, so their denominators should not be substituted for the primary endpoint denominators.

The most frequently listed serious adverse event terms include atrial arrhythmia at 16.9%, other at 12.9%, congestive heart failure at 12.5%, residual or recurrent mitral regurgitation at 11.8%, death at 11.2%, and gastrointestinal-related other at 11.2%. The record also reports 20 deaths in the device group and 9 in the surgery group. These safety summaries do not establish that every listed term occurred in a unique participant or that categories are mutually exclusive. No adjusted safety comparison or detailed timing and severity analysis is reported in the registry record.

16. What the Result Does, and Does Not, Mean

The posted primary comparison shows fewer participants with the 30-day composite major adverse event endpoint in the analyzed device group than in the analyzed surgery group. The unadjusted risk difference is -0.474, the confidence interval lies below zero, and the unadjusted p-value is < 0.001. This is a statistically distinct result for the endpoint and population described in the registry record.

That result does not establish that the device approach is superior for every outcome, every follow-up period, or every participant. The primary endpoint is a composite of multiple events, and the registry does not report which components account for the observed group difference. The analysis is per-protocol and limited to participants with available follow-up at the specified time. The record does not give the detail needed to determine how exclusions or missing observations may have affected the comparison.

The selected secondary comparisons are less conclusive. Mortality at 12 months is close between groups in the posted estimates, and the valve-related freedom outcomes have intervals that include no difference. These endpoints have different definitions and follow-up times, so they add context but do not serve as direct replications of the 30-day composite finding. Their unadjusted status and the lack of a reported multiplicity strategy further limit how strongly they can be interpreted.

General explanation: statistical evidence about a group-level contrast is not the same as a treatment recommendation. The posted registry data describe outcomes under particular trial conditions and analysis choices. They do not by themselves establish individual benefit, overall net benefit, or comparative performance in populations not represented by the analyzed participants. Such conclusions would require a broader assessment of endpoint components, longer-term outcomes, study conduct, and the full clinical evidence, none of which can be inferred from these selected registry comparisons alone.

17. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison and a clear account of the analysis population both matter. Random allocation provides a basis for comparing groups, while the primary result is reported for a per-protocol population with available follow-up. Those details answer different questions: the study design is randomized, but the primary analysis is not described as including every participant according to original assignment. Understanding both is necessary before interpreting the group contrast.

The primary outcome also demonstrates the trade-off inherent in composite endpoints. Combining multiple events can provide a single summary, but the resulting estimate may obscure which events are common, severe, or responsible for the overall pattern. The registry record gives the composite definition and group counts but does not give component-specific results for the primary comparison. Statistical interpretation therefore needs to remain tied to the exact composite rather than extending to each component separately.

The secondary results illustrate the role of precision and multiplicity. Their confidence intervals include no difference, and the record does not report an adjustment strategy despite listing many outcomes. A nominal p-value alone is not enough to distinguish a stable pattern from one that could arise amid many comparisons. The point estimates, intervals, endpoint definitions, and analysis populations all contribute to the interpretation.

Finally, the planning illustrations show how sample-size requirements depend on the effect a future study aims to detect. Smaller target effects require more participants under the stated assumptions. These calculations are not a substitute for the original trial's design rationale, which is not reported in the registry record. Taken together, the record is a useful example of reading a statistically notable primary comparison without treating it as a complete account of every outcome or source of uncertainty.

18. 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 constrain interpretation of the posted results. The primary outcome is a composite with many components, but the registry does not report component-specific primary results. It is therefore not possible to determine from this record which events account for the group contrast or whether the components show a consistent pattern.

The primary analysis is per-protocol and includes participants with available follow-up. The registry does not report the per-protocol criteria, exclusions, reasons for missing data, or methods used to address missing outcomes. The primary denominators differ from the arm sample sizes described in the registry, and the record does not explain that difference in detail. These gaps prevent a full assessment of attrition and the relationship between random assignment and the analyzed groups.

The registry lists many outcomes, but it does not report the original statistical analysis plan, the multiplicity strategy, or a hierarchy of confirmatory outcomes. The selected secondary comparisons are unadjusted and have confidence intervals including no difference. Without prespecification and multiplicity details, their inferential role is uncertain.

The record also does not report full eligibility criteria, allocation-concealment procedures, adherence details, interim-analysis plans, or the original sample-size justification. The adverse-event summaries use populations and denominators distinct from those of the primary endpoint, with no detailed comparison method reported. These are limitations of what can be concluded from the registry record; they do not establish that the underlying trial lacked procedures or analyses not recorded there.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Pivotal Study of a Percutaneous Mitral Valve Repair System — NCT00209274.
• Registry record last updated 2018-11-07; status last verified 2018-11.
• Results first posted 2017-09-05.
• 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.

22. Record Summary

The registry describes EVEREST II as a prospective, multi-center, randomized, parallel study with no masking, comparing MitraClip percutaneous repair with mitral valve repair or replacement surgery. Enrollment is listed as 279, and the record is marked completed.

The primary outcome is the number of participants with major adverse events at 30 days in a per-protocol cohort with available follow-up. The posted comparison shows 13.0 of 136.0 participants in the device group and 45.0 of 79.0 in the surgery group, with an unadjusted risk difference of -0.474 and p < 0.001. Selected secondary comparisons are less conclusive, with intervals that include no difference.

The registry does not report key details about the original statistical plan, multiplicity, missing-data handling, or the per-protocol criteria. The posted estimates should therefore be read as results for the stated outcomes and analyzed populations, with those limitations in view.