Study of Efficacy, Safety, Tolerability and Quality of Life of Inclisiran (KJX839) vs Placebo, on Top of Ongoing Individually Optimized Lipid-lowering Therapy, in Participants With Hypercholesterolemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy, Safety, Tolerability and Quality of Life of Inclisiran (KJX839) vs Placebo, on Top of Ongoing Individually Optimized Lipid-lowering Therapy, in Participants With Hypercholesterolemia (NCT05192941), a randomized phase 4 study. The primary outcome is Number of Participants Achieving Individual LDL-C Target (<55 mg/dL or <70 mg/dL).

2. Clinical Question

3. Trial Design

This was a randomized, placebo-controlled, parallel-group phase IV study in participants with hypercholesterolemia. The registry reports an enrollment of 1770 and identifies Novartis Pharmaceuticals as the sponsor. The study status is completed. The recorded study start is 2022-04-08, and the primary completion date is 2024-06-11.

Participants were assigned to inclisiran or corresponding placebo. Both groups also received open-label rosuvastatin, individually optimized to reach the participant’s LDL-C target and account for tolerability. The official title describes the study as double-blind, while the registry’s masking classification is quadruple. Those descriptions are both part of the record; details about which roles were masked are not reported in the registry record.

The primary outcome was assessed at Day 90. It counted participants meeting their individual LDL-C target, with the target set at <55 mg/dL or <70 mg/dL according to the most recent individual cardiovascular risk category. The analysis population was the full analysis set, defined as randomized participants who received at least one dose of blinded investigational treatment; only participants with an LDL-C value at Day 90 were included for this outcome.

Registry-listed secondary outcomes include LDL-C change over the double-blind treatment period, muscle-related adverse events, self-reported pain, pain days, and pain severity and interference measures. The record also lists clinically relevant changes in pain severity and interference through Day 360. Details of the full protocol, allocation procedures, treatment duration beyond the stated outcome timeframes, and the trial’s original sample-size justification 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.

Before assignment: This study had a screening period of approximately 14 days for all participants. Participants must have been on a stable dose of statin for ≥ 30 days prior to the screening visit.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) consisted of all randomized participants who received at least one dose of blinded investigational treatment. Only participants with an LDL-C value at Day 90 are included.

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.

Population: Baseline Characteristics are based on the Full analysis set (FAS)

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Achieving Individual LDL-C Target (<55 mg/dL or <70 mg/dL), measured over Day 90.

The primary endpoint counts participants who achieved their individual LDL-C target at Day 90. The target was either <55 mg/dL or <70 mg/dL, selected according to each participant’s most recent individual cardiovascular risk category. This is a binary outcome: each participant with an observed Day 90 LDL-C value either met the assigned target or did not.

A target-based endpoint asks whether participants crossed a clinically specified threshold, rather than describing only the average LDL-C concentration or its change. It can therefore summarize the proportion of the analysis population reaching the target selected for them. The registry states that a larger proportion meeting the target indicates a superior outcome. The endpoint does not, by itself, show how far above or below the target individual LDL-C values were, or describe the full distribution of LDL-C measurements.

The registry defines the primary analysis population as randomized participants who received at least one dose of blinded investigational treatment, with only participants who had an LDL-C value at Day 90 included in this endpoint. The counts therefore describe target achievement among participants with an observed value for this assessment, not necessarily every randomized participant. The registry record does not report the details of how missing Day 90 LDL-C values were handled beyond this inclusion statement.

7. Results Posted in the Registry

• Inclisiran: 84.9% (752/886) versus 31.0% (266/859) on control; risk difference 53.9 percentage points (95% CI 50.0 to 57.8), risk ratio 2.74 (2.47–3.04); 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.

Number of Participants With Clinically Relevant Change in Short-Form Brief Pain Inventory (SF-BPI) Pain Severity Score From Baseline to Day 360.

• 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:
  • Inclisiran: 14.5% (123/848) versus 12.7% (104/816) on control; risk difference 1.8 percentage points (95% CI -1.5 to 5.1), risk ratio 1.14 (0.89–1.45); unadjusted two-proportion z-test p = 0.296.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Inclisiran and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Clinically Relevant Change in Short-Form Brief Pain Inventory (SF-BPI) Pain Interference Score From Baseline to Day 360

• 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:
  • Inclisiran: 10.3% (87/848) versus 8.6% (70/816) on control; risk difference 1.7 percentage points (95% CI -1.1 to 4.5), risk ratio 1.20 (0.89–1.61); unadjusted two-proportion z-test p = 0.241.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Inclisiran and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning LDL-C change, muscle-related adverse events, self-reported pain, days with pain, and pain severity and interference. The secondary results with detailed group comparisons include clinically relevant changes in pain severity and pain interference from baseline to Day 360. Across these two pain outcomes, the unadjusted estimates are close to the no-difference values relative to their uncertainty, and the reported intervals include the null values. The sponsor-reported odds-ratio intervals also include one. Taken together, these results do not provide a clear signal of a between-group difference on these pain-change measures.

This pattern is distinct from the primary result, which concerns meeting an individual LDL-C target at Day 90 and has estimates clearly separated from the relevant null values. The primary and secondary outcomes measure different things at different times, so a result on one cannot be used as a direct substitute for the other. The secondary pain findings neither establish a pain benefit nor show that the primary LDL-C result is absent.

The registry record lists eight secondary outcome measures, but the detailed comparative results described for the pain-change outcomes are not a complete account of every listed measure. The presence of a listed outcome does not imply that its result was reported in the registry record. Full result details for the other listed secondary outcomes are not reported in the registry record.

Secondary outcomes are often interpreted with less weight than a prespecified primary endpoint because they may be numerous, may have less statistical precision, and may not be protected by a prespecified testing strategy. If many hypotheses are tested, unadjusted p-values can overstate how compelling an isolated result is. The registry does not report whether multiplicity adjustments or a hierarchical testing plan were used. The secondary results should therefore be treated as supportive or exploratory evidence, rather than as independent confirmation of a treatment effect.

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

• Relative Change From Baseline to Mean LDL-C Level Over the Double-blind Treatment Period
• Number of Participants Experiencing at Least One Muscle-related Adverse Event From Day 1 to Day 360
• Number of Participants Experiencing Self-reported Pain
• Annualized Number of Days With Pain
• Average Absolute Change From Baseline in Short-Form Brief Pain Inventory (SF-BPI) Pain Severity Score Over the Double-blind Treatment Period
• Average Absolute Change From Baseline in Short-Form Brief Pain Inventory (SF-BPI) Pain Interference Score Over the Double-blind Treatment Period
• Number of Participants With Clinically Relevant Change in Short-Form Brief Pain Inventory (SF-BPI) Pain Severity Score From Baseline to Day 360.
• Number of Participants With Clinically Relevant Change in Short-Form Brief Pain Inventory (SF-BPI) Pain Interference Score From Baseline to Day 360

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: meeting the individual LDL-C target or not meeting it at Day 90. The posted group counts give the number meeting the target and the number included in each group for the endpoint. A comparison of these counts can be expressed in several ways. Each measure answers a related but distinct question, so the scale should be identified when interpreting an effect estimate.

What does the risk difference express?

The risk difference subtracts the proportion meeting the target in the placebo group from the proportion in the inclisiran group. It describes an absolute difference in probability, rather than a relative change. The recalculated estimate is 0.539, with an interval from 0.500 to 0.578. A positive value indicates a higher observed probability of target achievement in the inclisiran group. The registry’s comparison reports the group proportions as 0.849 and 0.310, respectively. These values are proportions, not counts; the counts and denominators are also reported.

How do relative risk and odds ratio differ?

The relative risk is the proportion meeting the target in one group divided by the corresponding proportion in the other group. Its recalculated value is 2.741, with an interval from 2.471 to 3.04. It describes the ratio of probabilities. The odds ratio instead compares odds, where odds are the probability of an event relative to the probability of no event. Its recalculated value is 12.51, with an interval from 9.902 to 15.81. When an outcome is common, an odds ratio can be farther from one than the corresponding relative risk. It should therefore not be paraphrased as the same-sized ratio of probabilities.

What do the p-values say?

A p-value assesses how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The unadjusted recalculation has p <0.001. The sponsor’s reported logistic-regression result has p < 0.001. These values are evidence against a no-difference null under their respective analyses; they do not settle questions about generalizability, outcome importance, or unreported analysis choices.

The registry reports a logistic-regression odds ratio for the primary outcome. Regression can model the relationship between group assignment and a binary outcome. The record identifies the method as logistic regression but does not report the model covariates, coding details, or other specifications. The recalculation uses the posted summary counts and is an unadjusted comparison. It is not a substitute for the sponsor’s analysis plan or model.

How should the analysis population be understood?

The primary population is described as the full analysis set: all randomized participants who received at least one dose of blinded investigational treatment. For the Day 90 endpoint, only participants with an LDL-C value at that time are included. This means the endpoint comparison is based on participants meeting the stated analysis-population conditions and having the necessary measurement. Whether other approaches were used for missing values, or how many values were missing, is not reported in the registry record.

The registry labels the study randomized and parallel-group, with placebo as the comparator and open-label rosuvastatin in both groups. Randomization is intended to support a fair comparison between assigned groups, but the posted summary counts alone do not document the allocation sequence, concealment procedures, adherence, or balance of baseline characteristics. Those details are not reported in the registry record and should not be inferred from the outcome estimates.

Why do the secondary measures need separate interpretation?

The record lists secondary outcomes covering LDL-C change, muscle-related adverse events, self-reported pain, and pain severity and interference. The posted detailed comparisons for clinically relevant changes in pain severity and pain interference are binary outcomes. They count participants meeting the specified change criterion between baseline and Day 360. These measures differ from the primary target-attainment outcome in both content and timeframe. Their unadjusted comparisons are useful descriptive evidence, but they do not inherit the primary endpoint’s interpretation or automatically confirm a treatment effect on the other outcomes.

General statistical context: when many outcomes are tested, the chance of at least one apparently unusual result can increase if each test is considered independently. Adjustment strategies and prespecified testing hierarchies can address that issue, but whether such a strategy was used for this trial is not reported in the registry record. No adjustment should be assumed from the fact that outcome estimates are posted.

11. Confidence Intervals and Precision

An interval communicates uncertainty around an estimated effect. It gives a range of values compatible with the data and the method used, rather than a guarantee that the true effect lies within its endpoints. The width reflects both the observed data and the precision of the estimation procedure. Interpretation also depends on the effect scale: zero is the no-difference value for a risk difference, while one is the no-effect value for a relative risk or odds ratio.

For the primary endpoint, the recalculated risk-difference interval runs from 0.500 to 0.578 and does not include zero. The recalculated relative-risk interval runs from 2.471 to 3.04, and the odds-ratio interval runs from 9.902 to 15.81; neither includes one. The sponsor’s reported odds-ratio interval is a 95% confidence interval, from 9.59 to 15.24, and likewise does not include one. These intervals support a clearly separated primary comparison on their respective scales, while still allowing a range of plausible effect magnitudes.

For the posted secondary pain outcomes, the recalculated risk-difference intervals include zero, and the sponsor-reported odds-ratio intervals include one. Those intervals leave room for no group difference as well as effects in either direction. This is a less precise and less decisive pattern than the primary comparison. It should not be turned into proof that the groups are identical: an interval that includes the null value indicates uncertainty compatible with no difference, not equivalence.

The registry identifies the sponsor’s intervals as 95% confidence intervals. The confidence level for the intervals in the unadjusted recalculations is not specified in the registry record. Interval endpoints also do not account for potential concerns such as missing data, model choice, or testing multiple outcomes unless those features are built into the analysis. Details of those procedures are not reported in the registry record.

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 illustrations based on the observed primary effect, not a report of the trial’s original design calculation. They are expressed as participants per arm, not as a combined total and not as total events. The calculation assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect.

The 80% power column gives the estimated participants per arm for a design that would have an 80% probability of detecting the specified effect under the planning assumptions, if that effect were truly present. The 90% power column gives the corresponding planning amount for a 90% probability. These are design concepts: power is the probability of rejecting the null hypothesis under a particular assumed effect and analysis procedure. It is not a measure of how likely the observed result is to be true.

The rows scale the effect to detect as 100%, 75%, and 50% of the observed effect. As the assumed effect becomes smaller, more participants are needed per arm to detect it at the same stated power. The figures therefore illustrate how sensitive a future design’s required size can be to the effect researchers consider important and plausible. The trial’s own original design assumptions, including its intended effect size and sample-size justification, are not reported in the registry record. These planning figures are not observed power; they are hypothetical sample-size calculations and should not be read as a retrospective score for this completed trial.

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 = 0.310; treatment proportion p₁ = 0.849; average p̄ = 0.579.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6982 = 1.3684.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5849 = 0.4923.
4. n = (1.3684 + 0.4923)² / (0.5391)² = 11.9, rounded up to 12 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 <- 0.309662398137369                          # control proportion
p1 <- 0.848758465011287                          # 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(5192941)
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 = 12 (80% power), 16 (90% power)
 75% of observed effect: n per arm = 23 (80% power), 30 (90% power)
 50% of observed effect: n per arm = 53 (80% power), 70 (90% power)
power.prop.test: 11.9 
Simulated power at n = 12 per arm: 0.838 (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. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a logistic-regression odds ratio of 12.09, with a 95% confidence interval from 9.59 to 15.24 and p < 0.001. The unadjusted recalculation from the posted group counts gives an odds ratio of 12.51, with an interval from 9.902 to 15.81 and p <0.001. Both estimates point in the same direction and indicate a marked difference in odds of meeting the target between groups.

The values are not identical because the registry’s reported result is a regression analysis, whereas the recalculation is an unadjusted comparison of the posted summary counts. The registry record does not provide enough detail about the regression specification or other analysis choices to reconcile the estimates precisely. The recalculated result is best read as a transparent summary-count comparison; it does not replace the sponsor’s reported analysis. The record does not flag a discrepancy between these results.

The distinction matters because a regression estimate may depend on model details that are not captured by a simple comparison of counts. The posted sponsor result is the trial’s reported inferential analysis, while the unadjusted recalculation offers a separate way to understand the observed group contrast. Neither estimate, by itself, addresses missing-data sensitivity, multiplicity, or external applicability where those issues are not detailed in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and multiple secondary outcomes. It does not report whether the trial used a formal multiplicity adjustment, a testing hierarchy, or another procedure to control the chance of false-positive findings across outcomes. Without that information, the posted secondary p-values should be regarded as unadjusted evidence for their individual comparisons rather than as results protected by a known family-wise testing strategy. The registry does not report an interim-analysis plan or whether interim analyses occurred.

The primary population is described as randomized participants who received at least one dose of blinded investigational treatment. For the primary endpoint, only participants with an LDL-C value at Day 90 are included. The record does not report the number or reasons for missing Day 90 values, whether missingness differed between groups, or what sensitivity analyses were performed. It also does not describe imputation or other missing-data procedures beyond the stated inclusion criterion. Missing-data assumptions can affect estimates when the participants with observed outcomes differ systematically from those without them.

For the secondary pain outcomes, the reported analysis counts are based on participants with values for the relevant measures. How missing baseline or Day 360 pain assessments were handled is not reported in the registry record. Details of the analysis populations for the other listed secondary outcomes are also not reported in the registry record.

The trial is randomized, but the posted results do not provide the allocation sequence or concealment details, baseline group characteristics, adherence information, or full model specifications. The registry reports logistic regression for the primary and pain-change analyses, but does not state which covariates were included. The protocol’s original sample-size justification and assumptions are not reported in the registry record. These gaps do not invalidate the posted estimates, but they limit independent assessment of the analysis choices and the robustness of the findings.

16. 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 1.999% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: osteoarthritis (1.4%), atrial fibrillation (1.3%), angina pectoris (1.0%), angina unstable (0.8%), coronary artery disease (0.8%).

The registry reports 148 participants with at least one serious adverse event among 900 at risk in the inclisiran group, and 148 among 870 at risk in the placebo group. It reports other adverse events for 416 of 900 and 462 of 870 participants, respectively. Deaths are reported for 6 participants in the inclisiran group and 5 in the placebo group. These are descriptive counts from the safety record; they are not, by themselves, estimates of causal effects or evidence about the cause of an event.

The listed serious adverse-event terms with the highest reported percentages include osteoarthritis at 1.4%, atrial fibrillation at 1.3%, angina pectoris at 1.0%, angina unstable at 0.8%, coronary artery disease at 0.8%, and peripheral arterial occlusive disease at 0.8%. The registry record does not establish that these events were caused by the assigned treatment. It also does not provide detailed event timing, individual clinical context, or a complete account of adjudication and relatedness assessments in the registry record.

Safety counts should be interpreted alongside the at-risk groups and the study’s follow-up and reporting definitions. They do not replace a full review of event severity, duration, recurrence, or treatment relationship. Those details are not reported in the registry record.

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

The primary result describes a higher number and proportion of participants meeting their individual LDL-C target at Day 90 in the inclisiran group than in the placebo group, with both groups receiving individually optimized open-label rosuvastatin. The unadjusted and sponsor-reported comparisons are consistent in direction, and their primary-result intervals exclude the relevant no-difference value. This is evidence about the trial’s specified target-attainment endpoint in its analyzed population.

It does not show how much each participant’s LDL-C changed on average, how long any target attainment persisted, or whether cardiovascular events were reduced. The primary outcome is a threshold measure at Day 90. The registry lists LDL-C change and other secondary outcomes, but the detailed comparative results for all of those measures are not reported in the registry record. Target attainment should not be treated as interchangeable with a clinical-event outcome.

The result also does not establish that every participant responds in the same way, or that the observed group contrast applies to people outside the study population. Participant characteristics beyond hypercholesterolemia are not reported in the registry record, limiting assessment of applicability to particular groups. The primary analysis includes only participants who received at least one dose and had a Day 90 LDL-C value, and the record does not provide a full missing-data analysis.

The secondary pain outcomes do not show a clear group difference in the posted comparisons, but those measures address distinct questions and their interpretation is limited by uncertainty and unreported multiplicity procedures. Safety counts are descriptive and do not establish treatment causation. Overall, the registry results support a clear difference in the stated Day 90 target-attainment comparison, while leaving other efficacy, safety, and generalizability questions to the evidence and analyses not reported in the registry record.

18. Why This Trial Matters Statistically

This trial is statistically informative because its primary endpoint translates a laboratory measure into an individual target-attainment outcome. The target was selected according to each participant’s most recent individual cardiovascular risk category, rather than applying only one LDL-C threshold to the entire study population. That design choice makes the endpoint a comparison of how often participants met their assigned target at Day 90.

The size and precision of the primary contrast can be considered on more than one scale. The risk difference conveys the absolute separation in target attainment, while the relative risk and odds ratio convey relative contrasts. Keeping those measures distinct helps prevent a common interpretive error: an odds ratio is not the same thing as a ratio of probabilities, particularly when the outcome is frequent in one group.

The registry also gives a sponsor-reported regression estimate alongside counts that permit an unadjusted recalculation. Comparing the two illustrates why statistical reporting benefits from both a clearly identified model-based analysis and transparent group summaries. The estimates are directionally consistent, but the model details are not reported in the registry record, so the recalculation cannot explain the sponsor’s modeling choices.

Finally, the trial highlights the difference between a strong primary-endpoint comparison and more uncertain secondary findings. The results for the listed pain-change measures do not show a similarly clear separation, and the registry does not explain how multiplicity was handled. Distinguishing primary from secondary evidence, and target attainment from continuous change or clinical events, is central to reading the results without overextending what the endpoint establishes.

19. 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 limitations specific to interpreting this registry record remain. The primary endpoint is measured at Day 90, so it describes target attainment at that assessment rather than the persistence of the result. The registry does not report individual LDL-C values or a continuous summary of the distribution for the primary assessment. It also does not report how many participants lacked a Day 90 value or provide sensitivity analyses for missing outcomes.

The primary comparison is reported both as a sponsor logistic-regression odds ratio and as an unadjusted recalculation from summary counts. The record does not describe the regression covariates or other model specifications, limiting a detailed reconciliation of the two estimates. The original sample-size justification, intended design effect, interim-analysis approach, and multiplicity strategy are not reported in the registry record.

Although the study is described as randomized and masked, details of allocation concealment and which roles were masked are not reported in the registry record. The official title describes double blinding, while the masking classification states quadruple masking. The record does not give participant characteristics beyond the condition, making it difficult to evaluate how well the analyzed population represents specific clinical subgroups.

The detailed secondary comparisons available in the record cover two pain-change outcomes, while the record lists a broader set of secondary measures. Detailed results for all listed secondary outcomes are not reported in the registry record. Safety summaries provide counts and selected serious adverse-event terms, but not a full account of event relatedness, timing, severity, or adjudication. These omissions constrain broader conclusions about the trial beyond the reported primary endpoint and descriptive safety counts.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study of Efficacy, Safety, Tolerability and Quality of Life of Inclisiran (KJX839) vs Placebo, on Top of Ongoing Individually Optimized Lipid-lowering Therapy, in Participants With Hypercholesterolemia — NCT05192941.
• Registry record last updated 2026-04-14; status last verified 2026-03.
• Results first posted 2026-04-14.
• 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.

23. Record Summary

NCT05192941 is a completed, randomized, placebo-controlled, parallel-group phase IV study sponsored by Novartis Pharmaceuticals in participants with hypercholesterolemia. The registry reports enrollment of 1770, a study start of 2022-04-08, and primary completion on 2024-06-11. Participants received inclisiran sodium 300 mg subcutaneously or corresponding placebo, with open-label, individually optimized rosuvastatin in both groups.

The primary endpoint counted participants meeting their individual LDL-C target of <55 mg/dL or <70 mg/dL at Day 90. The posted counts and sponsor logistic-regression analysis show a higher target-attainment result in the inclisiran group. Secondary pain-change comparisons are less decisive, and safety information is reported as adverse-event counts and selected serious-event terms. The registry does not report several details needed for fuller assessment, including the original sample-size justification, multiplicity strategy, missing-data procedures, and complete model specifications.