Efficacy and Safety of KBP-5074 in Uncontrolled Hypertension and Moderate or Severe Chronic Kidney Disease (CKD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of KBP-5074 in Uncontrolled Hypertension and Moderate or Severe Chronic Kidney Disease (CKD) (NCT04968184), a randomized phase 3 study. The primary outcome is Change in Seated Trough Cuff Systolic Blood Pressure (SBP) From Baseline to Week 12.

2. Clinical Question

The question is specific to blood pressure over the stated follow-up period and to the trial’s eligible population. It is not a direct test of long-term kidney outcomes, cardiovascular events, or durability beyond the reported endpoint. Although the brief summary mentions a randomized withdrawal component and durability, the detailed withdrawal procedures and results are not reported in the registry record. The primary endpoint should therefore be interpreted as a comparison of change in seated trough cuff systolic blood pressure at the specified time, rather than as a broad assessment of all possible benefits or risks.

3. Trial Design

The registry identifies NCT04968184 as a Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study. It lists quadruple masking, while the study description characterizes the treatment period as double-blind. The registry record does not explain the difference between those masking labels. Enrollment is listed as 666, and the study status is terminated. The recorded start date is 2021-11-05 and the primary completion date is 2024-01-30; the reason for termination is not reported in the registry record.

The study compared KBP-5074 with placebo in adults with uncontrolled hypertension and moderate or severe chronic kidney disease, described as stage 3b/4. The brief summary specifies an eGFR range of 15 to 44 mL/min/1.73 m^2 and systolic blood pressure from 140 to below 180 mm Hg while taking 2 or more antihypertensive medications. Participants in both groups received matching placebo during an approximately 2-week open-label run-in. The registry describes assigned treatment from week 2 through week 24 in the double-blind period.

The primary outcome was change in seated trough cuff systolic blood pressure from baseline to Week 12. The registry reports 22 outcome measures and 18 analyses. Its primary population description says that the intent-to-treat population includes randomized participants after removal of participants from site 508; it also clarifies that the number analyzed for this outcome is specific to that measure and time frame. The reason for removing that site, details of the randomization procedure, and the original design assumptions are not reported in the registry record. A randomized withdrawal component is mentioned in the brief summary, but its detailed conduct and its relationship to the posted endpoint results are not reported.

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: Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All the study assessments were performed as per the schedule of events. The trial was originally sponsored by KBP Biosciences PTE Ltd, but sponsorship was transferred to Novo Nordisk after the trial was terminated following a futility determination by an independent data monitoring committee.

Double-Blind Period

Reasons for not completing this period:

Open-Label Period

Reasons for not completing this period:

Randomized Double-Blind WithdrawalPeriod

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The intent-to-treat (ITT) Population was defined as all randomized participants after removal of participants from site 508. Here, overall number of participants analyzed field represents the number of participants assessed for this particular outcome measure at indicated 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.

Population: The intent to treat (ITT) population was defined as all randomized participants after removal of participants from site 508.

6. Primary Endpoint

The registry lists the primary outcome as Change in Seated Trough Cuff Systolic Blood Pressure (SBP) From Baseline to Week 12, measured over From baseline to Week 12.

The primary endpoint is change in seated trough cuff systolic blood pressure from baseline to Week 12, measured in mm Hg. A change score expresses how much the measured blood pressure at the follow-up time differs from the participant’s baseline value. Negative group means in the posted results indicate decreases from baseline. The comparison of interest is the difference in average change between the KBP-5074 and placebo groups, not whether either group changed from baseline in isolation.

Seated trough cuff measurement specifies a standardized blood-pressure context: the measurement is taken while seated and at the trough point described in the protocol terminology. The registry record does not provide the detailed measurement procedures, timing relative to dosing, or the number of readings used. Such details can matter because blood pressure varies with measurement conditions and within individuals.

As a continuous outcome, the endpoint preserves information about the degree of change rather than reducing the result to a threshold category. The mean summarizes the average change in each analyzed group, while the standard deviation describes variability among participants. The endpoint is used to assess the stated blood-pressure efficacy question over the defined follow-up period. It does not by itself measure kidney disease progression, long-term cardiovascular outcomes, or overall durability. Those broader questions require outcomes and follow-up information beyond this primary measure.

7. Results Posted in the Registry

• KBP-5074: mean -12.90 versus -12.40 on control; difference -0.50 (95% CI -3.66 to 2.66), standardized effect d = -0.03; z-test p = 0.756.

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.

Change in Seated Trough Cuff SBP From Baseline to Week 24

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • KBP-5074: mean -15.30 versus -12.80 on control; difference -2.50 (95% CI -5.66 to 0.66), standardized effect d = -0.14; z-test p = 0.121.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between KBP-5074 and the control. The interval gives the range of effects that remain compatible with the data.

Changes in Seated Trough Cuff Diastolic Blood Pressure (DBP) From Baseline to Week 12

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • KBP-5074: mean -6.30 versus -5.60 on control; difference -0.70 (95% CI -2.70 to 1.30), standardized effect d = -0.06; z-test p = 0.492.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between KBP-5074 and the control. The interval gives the range of effects that remain compatible with the data.

Changes in Seated Trough Cuff Diastolic Blood Pressure (DBP) From Baseline to Week 24

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • KBP-5074: mean -6.30 versus -6.70 on control; difference 0.40 (95% CI -1.81 to 2.61), standardized effect d = 0.03; z-test p = 0.723.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between KBP-5074 and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary blood-pressure comparisons have a broadly consistent pattern with the primary result: the estimated between-group contrasts are modest relative to their uncertainty, and the reported confidence intervals include zero. Across the systolic and diastolic measures at the listed follow-up times, the direction of the estimated contrast is not uniform. This means the secondary results do not form a consistent pattern of separation from placebo across the reported blood-pressure measures.

The registry lists further secondary outcomes involving urinary albumin-to-creatinine ratio, including changes and percentage changes in participants meeting the stated baseline criterion, as well as longer-term blood-pressure outcomes. Numerical results for these measures are not included in the registry record details considered for this analysis, so their direction, magnitude, and precision cannot be assessed. Their inclusion in the outcome list does not itself establish a result.

Secondary endpoints can provide context about other dimensions of an intervention, but they generally carry less confirmatory weight than a prespecified primary endpoint. Multiple outcomes and time points create multiple opportunities for apparently notable findings to arise by chance. Unless the analysis plan specifies a multiplicity strategy, unadjusted secondary p-values should be interpreted cautiously and not treated as independent proof. The registry record does not report whether multiplicity was controlled or how secondary outcomes were ordered for formal testing.

Accordingly, the secondary pattern does not overturn the primary interpretation. It offers additional comparisons with uncertainty, while leaving questions about kidney-related outcomes and durability unresolved in the numerical record. The summary should not be extended beyond the outcomes with posted estimates.

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

• Change in Seated Trough Cuff SBP From Baseline to Week 24
• Changes in Seated Trough Cuff Diastolic Blood Pressure (DBP) From Baseline to Week 12
• Changes in Urinary Albumin: Creatinine Ratio (UACR) From Baseline to Week 12 for Participants With UACR ≥30 mg/g at Baseline
• Percentage Changes in UACR From Baseline to Week 12 and Week 24 for Participants With UACR ≥30 mg/g at Baseline
• Changes in Seated Trough Cuff Diastolic Blood Pressure (DBP) From Baseline to Week 24
• Changes in Seated Trough Cuff DBP From Baseline to Week 48
• Changes in Seated Trough Cuff SBP From Baseline to Week 48
• Changes in UACR From Baseline to Week 24 for Participants With UACR ≥30 mg/g at Baseline

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean change represent?

The primary endpoint is continuous, so the registry reports a mean change for each treatment group. A group mean is the average of the individual changes recorded among participants analyzed for that outcome and time point. It gives a concise description of the group’s central tendency but does not show how each participant changed. The standard deviations, 18.02 mm Hg for KBP-5074 and 18.73 mm Hg for placebo, describe the spread of observed changes around each group mean. Substantial individual variability can coexist with similar group averages.

The treatment contrast is the difference between the average changes in the two groups. The unadjusted recalculation is -0.5 mm Hg, formed from the posted summaries; it is not a model-adjusted estimate. A negative value means the estimated change was more negative in the KBP-5074 group than in the placebo group. The estimate is small relative to the spread of changes, but its magnitude should be considered alongside the confidence interval rather than interpreted alone.

What does the confidence interval add?

A confidence interval describes the uncertainty around an estimate under the statistical model used to construct it. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The primary unadjusted interval extends from -3.655 to 2.655 mm Hg. Because it includes zero, the data are compatible with no between-group difference as well as with differences in either direction within the interval. The interval does not assign a probability to the true effect being inside its bounds; it is a repeated-sampling measure of uncertainty under the method’s assumptions.

The interval is especially important because the point estimate alone can appear more definite than the data warrant. A point estimate is one value calculated from the observed sample. The range around it indicates that sampling variability leaves room for a range of underlying effects. The registry does not report a threshold for a clinically meaningful difference, so the interval cannot by itself classify every value it contains as clinically important or unimportant.

How should the p-value be read?

The unadjusted p-value is 0.756. In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model, subject to the test’s assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A large p-value does not prove that the groups are identical. In this analysis, it accompanies a small estimated difference and an interval that includes zero; together these indicate that the posted data do not resolve the primary comparison as a clear difference.

The sponsor’s p-value comes from ANCOVA, which the registry describes as a comparison of adjusted least-squares means. In general, ANCOVA estimates a group contrast while accounting for covariates included in the model. The registry does not identify the covariates or describe other model details, so the adjustment cannot be independently reconstructed from the record. The adjusted contrast and the unadjusted recalculation answer closely related but not identical statistical questions.

Why can adjusted and unadjusted estimates differ?

Randomization supports comparison of assigned groups, but the groups can still differ by chance in measured baseline characteristics. An adjusted model can account for specified covariates and may produce an estimate and uncertainty different from a direct comparison of posted group means. Adjustment can improve precision when the model and covariates are appropriate, but the registry record does not provide enough detail to evaluate the model specification. The sponsor’s analysis is therefore best identified as the registry-reported adjusted result, while the separate recalculation is a simple unadjusted summary-statistic comparison.

The primary outcome population is described as the intent-to-treat population after removal of participants from site 508. The term intent-to-treat generally refers to analyzing participants according to randomized assignment, but the registry’s site removal means the described population is not simply all randomized participants. The reason for removal and its handling in other analyses are not reported in the registry record. The group counts analyzed for the primary endpoint are 267 and 255; these are outcome-specific counts, not a replacement for the registry’s overall enrollment figure.

Why does variability matter?

Standard deviation describes participant-to-participant variability, not uncertainty in the mean itself. Standard error describes the estimated sampling uncertainty of a mean. The posted standard errors for the primary group means are 1.103 and 1.173 mm Hg. General statistical reasoning: when variability is large relative to the group contrast, a study may estimate the contrast imprecisely unless it has enough observations or uses an appropriate design that improves precision. The primary confidence interval reflects uncertainty in the contrast, while the standard deviations describe the spread of individual changes.

These methods depend on assumptions about the outcome distribution and analysis. The registry record does not report diagnostic checks, transformations, missing-data procedures, or a detailed statistical analysis plan. Those details matter for judging whether the model and uncertainty estimates are suitable. The reported means and ANCOVA result remain interpretable as the registry’s posted summaries, but the record does not support a full audit of the analysis.

11. Confidence Intervals and Precision

The primary unadjusted mean difference is -0.5 mm Hg, with a 95% confidence interval from -3.655 to 2.655. The interval spans zero, so the estimate is not precise enough to distinguish a negative difference from no difference or a positive difference at the stated confidence level. The sponsor’s adjusted estimate is -0.8 mm Hg, with a 95% confidence interval from -3.7 to 2. The adjusted interval also spans zero. The two intervals are not identical because one is an unadjusted recalculation and the other comes from ANCOVA.

In general, confidence intervals communicate a range of effect estimates compatible with the data and method, rather than a guarantee about the true effect. Their width reflects sampling uncertainty and the analysis assumptions. The primary group standard deviations, 18.02 and 18.73 mm Hg, are much larger than the estimated difference between group means; this helps explain why the interval allows a range of contrasts. That comparison is descriptive and does not establish a clinical threshold.

The interval’s inclusion of zero does not show that the treatments are equivalent. Equivalence requires a prespecified margin and an analysis designed to test whether the plausible difference lies within that margin. No equivalence margin is reported in the registry record. Similarly, the record does not give a clinically important difference threshold for this endpoint. It is therefore more accurate to say that the estimate is uncertain and that the posted analysis does not establish a clear difference, rather than to claim that any possible difference is absent or negligible.

Precision applies to the stated population and analysis. The primary population excludes participants from site 508, and the reason is not reported. Missing-data methods and the original precision goals are also not reported in the registry record. These gaps leave uncertainty about how the reported interval relates to the full randomized population and the planned analysis.

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 participants per arm for the continuous-outcome illustrations in this trial, not total event counts. They use the observed effect as a planning reference and show scenarios for detecting 100% of that observed effect, 75% of the observed effect, or 50% of the observed effect. For the primary endpoint, the figure for 100% of the observed effect is 21,190 participants per arm for 80% power and 28,368 participants per arm for 90% power. For the smaller-effect scenarios, the corresponding figures are larger.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The 80% power column describes the planned chance of detecting an effect of the specified size under those assumptions if that effect were the true one. The 90% power column uses a higher target chance of detection and therefore gives a larger planning requirement for the same assumed effect. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants.

These are planning illustrations based on the observed effect, not the trial’s original design assumptions; those original assumptions are not reported in the registry record. They are not observed power. They do not indicate the probability that the primary result is true, and they should not be used to reinterpret the trial as having achieved or failed a particular power target. The figures are sensitive to the estimated effect used as their starting point, so small or unstable observed effects can produce very large illustrative sample sizes. They are best read as comparisons among hypothetical planning scenarios under the stated assumptions.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.500; pooled standard deviation σ = 18.370.
2. n = 2 × (1.96 + 0.842)² × 18.370² / -0.500² = 21,189.8, rounded up to 21,190 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
delta <- -0.5                      # observed difference in means
sigma <- 18.3702363265231                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4968184)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 21,190 (80% power), 28,368 (90% power)
 75% of observed effect: n per arm = 37,671 (80% power), 50,431 (90% power)
 50% of observed effect: n per arm = 84,760 (80% power), 113,469 (90% power)
power.t.test: 21190.8 
Simulated power at n = 21,190 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 sponsor-reported primary analysis is ANCOVA and gives a difference between adjusted least-squares means of -0.8 mm Hg, with a 95% confidence interval from -3.7 to 2 and p=0.572. The recalculated comparison is an unadjusted difference from the posted group means: -0.5 mm Hg, with a 95% confidence interval from -3.655 to 2.655 and an unadjusted p-value of 0.756. The two estimates are close in direction and both intervals include zero, but they should not be treated as interchangeable because they arise from different analyses.

ANCOVA generally adjusts the group comparison for covariates specified in the model. The registry record does not identify those covariates or provide enough model detail to reproduce the sponsor’s estimate. The recalculation uses only the posted group summaries and does not adjust for participant characteristics. Differences in estimates and p-values can therefore arise from the analysis method, not necessarily from conflicting data.

The record does not flag a discrepancy between the recalculation and the sponsor result. The sponsor’s analysis is the trial’s reported adjusted analysis; the unadjusted calculation is an additional descriptive check, not a substitute for the sponsor’s model. Both summaries support a cautious reading: the primary endpoint estimate is near zero relative to its uncertainty, and the registry results do not establish a clear between-group difference.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, time points, or statistical contrasts. Even if each individual test uses a conventional significance threshold, running many tests increases the chance that at least one result appears notable by chance. Common approaches include adjusting the testing threshold, controlling a family-wise error rate, or defining a hierarchical sequence in which outcomes are tested in a prespecified order. These are general statistical approaches; the registry record does not report which, if any, was used for this trial.

The record lists 22 outcome measures and 18 analyses, including systolic and diastolic blood pressure at multiple time points and urinary albumin-to-creatinine outcomes. The primary endpoint is identified, but a multiplicity adjustment or a hierarchy for secondary hypotheses is not reported in the registry record. The sponsor’s adjusted ANCOVA concerns covariate adjustment; that is distinct from adjustment for testing multiple outcomes. The unadjusted secondary p-values should therefore be read as descriptive evidence unless a fuller analysis plan establishes a confirmatory testing strategy.

Missing-data handling is also not reported. The registry gives outcome-specific numbers analyzed and describes the primary population as randomized participants after removal of participants from site 508, but it does not explain the removal, the amount or pattern of missing outcome data, or the method used to address missing observations. It is not possible to infer whether missing measurements were handled through imputation, a model-based approach, or another procedure.

The primary population description uses an intent-to-treat label with a stated site-level exclusion. The registry record does not explain how this exclusion was determined or whether the same population definition was used for all outcomes. These reporting gaps matter because the analysis population and missing-data assumptions can affect both the estimate and its uncertainty. The original sample-size justification, interim analysis plans, and detailed statistical analysis plan are not reported in the registry record, so they cannot be used to resolve these questions.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.6%), chronic kidney disease (1.8%), covid-19 (1.5%), cerebral infarction (1.1%), acute kidney injury (1.1%).

The registry separates adverse-event summaries by group labels, including the main KBP-5074 and placebo groups and additional labels ending in OL and W. In the main groups, serious adverse events affected 20 of 281 at risk in the KBP-5074 group and 30 of 273 at risk in the placebo group. Other adverse events affected 39 of 281 and 16 of 273, respectively. The death counts listed for those groups are 2 and 0. These figures are counts of participants affected as represented in the record; they do not, by themselves, describe event severity beyond the category labels or establish a causal relationship to assigned treatment.

The additional registry groups list serious adverse events affecting 27 of 469 in KBP-5074 - OL and 4 of 99 in KBP-5074 - W, and 1 of 107 in Placebo - W. Other adverse events affected 83 of 469, 13 of 99, and 6 of 107 in those respective groups. Deaths are listed as 4, 0, and 0. Because the labels and group sizes differ, these summaries should not be combined or compared as though they represent identical randomized follow-up periods. The registry record does not provide enough detail to establish the relationship of every safety group to treatment exposure.

The most frequently listed serious-event terms include pneumonia (2.6%), chronic kidney disease (1.8%), COVID-19 (1.5%), cerebral infarction (1.1%), acute kidney injury (1.1%), and hyperkalaemia (1.1%). Safety counts require context about exposure duration, event definitions, ascertainment, and attribution. Those details are not fully reported in the registry record. These summaries describe reported events and should not be interpreted alone as a complete comparative safety assessment.

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

The primary result is a comparison of mean change in seated trough cuff systolic blood pressure from baseline to Week 12. The unadjusted estimate is -0.5 mm Hg, and the sponsor’s adjusted estimate is -0.8 mm Hg. Their confidence intervals both include zero. The posted analyses therefore do not establish a clear difference between KBP-5074 and placebo for this endpoint in the described analysis population.

This does not prove that the treatments have identical effects. The intervals allow a range of possible differences, and the registry record does not report an equivalence margin or a clinically important difference threshold. The findings also do not show that the observed within-group decreases were caused only by treatment; the randomized contrast, not the change within either arm alone, is the relevant comparison for the treatment question.

The result applies to the measured endpoint and follow-up time. It does not directly answer whether treatment affects kidney disease progression, cardiovascular events, or blood pressure beyond the reported time points. Although the brief summary refers to durability and a randomized withdrawal component, numerical results and detailed procedures for those aspects are not reported in the registry record details used for this analysis.

The safety summaries list adverse events and deaths across several group labels, but they do not alone determine whether an event was caused by treatment or provide a full account of comparative risk. The registry’s terminated status also needs context: the reason for termination and its implications are not reported. The responsible interpretation is therefore narrow. The posted primary estimates are uncertain and do not demonstrate a clear between-group difference, while important design, analysis, long-term outcome, and safety details remain unavailable in the registry record.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through both its point estimate and its uncertainty. The primary group means show decreases from baseline in both arms, but the randomized question concerns the difference between those changes. The estimated contrast is near zero, and the confidence interval spans zero. Looking only at the within-group changes could suggest a stronger conclusion than the between-group comparison supports.

The record also distinguishes an unadjusted recalculation from the sponsor’s adjusted ANCOVA. These analyses use different methods and produce slightly different estimates and p-values. Recognizing that distinction prevents an adjusted model result from being mistaken for a direct calculation from group summaries, and prevents the simple recalculation from being treated as a replacement for the trial’s reported analysis.

Planning illustrations based on observed effects provide another useful statistical lesson. Sample-size requirements depend strongly on the effect size chosen for planning: smaller target effects require more participants under the same assumptions. Such illustrations are not evidence about the probability that the observed result is correct and are not observed power. They also cannot substitute for the original design assumptions, which are not reported in the registry record.

Finally, the record contains meaningful limits on interpretation. The primary analysis population excludes participants from site 508, the trial is listed as terminated, and key details about missing data, multiplicity, and the reason for termination are not reported. A careful statistical reading can describe the estimates and their precision without claiming more than the registry supports. That discipline is particularly important when primary and secondary outcomes, safety summaries, and planning scenarios appear together.

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 trial-specific reporting limitations constrain interpretation. The primary population is described as randomized participants after removal of participants from site 508, but the reason for this site-level exclusion is not reported in the registry record. The outcome-specific analyzed group counts are smaller than the enrollment figure, but the record does not explain all differences between enrollment, randomization, and analysis populations. No conclusion about the causes of those differences can be drawn from the listed counts alone.

The registry identifies the study as terminated, yet does not report the reason or the consequences for planned follow-up and analyses. The brief summary mentions randomized withdrawal and durability, but the detailed withdrawal design and numerical results are not available in the record details. The timing and methods used for blood-pressure measurements are also not described in sufficient detail for independent evaluation.

The sponsor’s ANCOVA result is reported without the covariates or model specification. Missing-data methods, multiplicity procedures, the original sample-size justification, and interim analysis plans are not reported. These gaps limit assessment of whether the posted analysis follows the planned strategy and how robust the estimates are to alternative assumptions.

The safety record includes differently labeled groups, with different numbers at risk. It does not provide enough detail to treat all groups as comparable treatment-period populations, nor does the listed event information establish causality. The registry also does not report a clinical-importance threshold for the primary endpoint. These limitations do not erase the posted estimates, but they restrict conclusions to the specific outcomes and analyses described.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of KBP-5074 in Uncontrolled Hypertension and Moderate or Severe Chronic Kidney Disease (CKD) — NCT04968184.
• Registry record last updated 2026-11-04; status last verified 2026-08.
• Results first posted 2026-11-04.
• 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

NCT04968184 is a Phase 3 randomized, placebo-controlled, parallel-group study of KBP-5074 in adults with uncontrolled hypertension and stage 3b/4 chronic kidney disease. The primary outcome is change in seated trough cuff systolic blood pressure from baseline to Week 12. The registry lists enrollment of 666, a terminated status, and primary completion on 2024-01-30.

The Week 12 unadjusted mean difference is -0.5 mm Hg, with a 95% confidence interval from -3.655 to 2.655 and p=0.756. The sponsor’s adjusted ANCOVA estimate is -0.8 mm Hg, with a 95% confidence interval from -3.7 to 2 and p=0.572. Both intervals include zero, so the posted analyses do not establish a clear difference for the primary endpoint.

The record also lists secondary outcomes and safety summaries. The reason for termination, detailed missing-data and multiplicity methods, the original sample-size justification, and the numerical results for several listed outcomes are not reported in the registry record. Interpretation should remain focused on the reported estimates and their uncertainty.