A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus (NCT00660309), a randomized phase 4 study. The primary outcome is Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan.

2. Clinical Question

The trial also set out to assess renal plasma flow, glomerular filtration rate and retinal blood flow after single and multiple doses. The registry record describes comparisons with captopril or irbesartan, but the posted primary result is the single-dose renal plasma flow comparison between aliskiren and irbesartan. The two groups shared the captopril dose on Day 1; that dose was not the primary comparison.

The clinical question is therefore narrower than whether either drug changes kidney function in general. It concerns a specified short-term physiological measure, collected at baseline and repeatedly after dosing on Day 2, in the trial’s pharmacodynamic analysis set. The result describes the recorded group means and their uncertainty. It does not, on its own, answer questions about longer-term kidney outcomes or clinical benefit.

3. Trial Design

This was a Phase 4, randomized, open-label, parallel-group study. The registry record lists an enrollment of 45 and a completed status. The study started in 2008-04, with primary completion in 2009-12. Novartis is listed as sponsor. Masking was not used.

Participants received a single 25 mg oral dose of captopril on Day 1. Starting on Day 2, the two groups followed different 14-day regimens: aliskiren 300 mg once a day or irbesartan 300 mg once a day. The primary endpoint concerns the response to a single dose of aliskiren or irbesartan on Day 2, rather than the full treatment period. The registry record also describes outcomes at steady state.

The primary outcome was assessed in a pharmacodynamic analysis set. Its definition includes participants with available pharmacodynamic data and excludes major protocol deviations that affected those data. The primary group summaries include 22 participants for aliskiren and 20 for irbesartan. Those analysis counts need not be identical to the overall enrollment because the outcome uses a defined analysis set.

Random allocation is recorded, but the method used to generate the allocation sequence, concealment procedures, and any stratification factors are not reported in the registry record. The original design’s sample-size justification and planned statistical analysis are also not reported in the registry record. The posted results include outcome summaries and comparisons, while the registry record lists no reported analyses. These gaps mean the posted summaries can be interpreted descriptively, but they do not establish how the original protocol planned to estimate or test the treatment contrast.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacodynamics (PD) analysis set consisted of all patients with available PD data and no major protocol deviations with impact on PD data.

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 Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan, measured over Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose..

The primary endpoint is change from baseline in renal plasma flow (RPF) after a single dose of aliskiren or irbesartan. RPF represents the volume of plasma passing through the kidneys over time, expressed in mL/min/1.73m^2. It is a physiological measure, not a direct measure of a clinical event or a long-term kidney outcome.

RPF was measured by clearance of para-aminohippurate (PAH), using autoanalyzer methods. On Day 2, baseline was based on measurements taken 10 minutes and 5 minutes before treatment and at the predose time point. The registry describes baseline RPF as the median of those three readings. The peak value was obtained using a moving-average concept. The single-dose effect was defined as the Day 2 peak minus the Day 2 baseline RPF.

Repeated measurements after dosing can characterize the short-term response over the specified observation period. Using a baseline-adjusted change focuses the endpoint on the response relative to each participant’s measured starting level. A group mean summarizes the average change, while the standard deviation describes variation among participants. These choices are useful for describing a continuous physiological outcome, but they do not by themselves establish that a change is clinically important. The registry record does not report a threshold for clinical importance.

7. Results Posted in the Registry

• Irbesartan: mean 35.88 versus 37.18 on control; difference -1.30 (95% CI -23.01 to 20.41), standardized effect d = -0.04; z-test p = 0.907.

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 From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Captopril

• 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:
  • Irbesartan: mean 40.13 versus 43.32 on control; difference -3.19 (95% CI -25.83 to 19.45), standardized effect d = -0.08; z-test p = 0.782.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Irbesartan and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Captopril

• 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:
  • Irbesartan: mean 7.41 versus 11.29 on control; difference -3.88 (95% CI -12.71 to 4.95), standardized effect d = -0.27; z-test p = 0.389.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Irbesartan and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Aliskiren or Irbesartan

• 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:
  • Irbesartan: mean 10.16 versus 10.52 on control; difference -0.36 (95% CI -7.18 to 6.46), standardized effect d = -0.03; z-test p = 0.918.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Irbesartan and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the physiological questions beyond the primary single-dose RPF comparison. They include RPF and glomerular filtration rate after the Day 1 captopril dose, glomerular filtration rate after single doses of aliskiren or irbesartan, steady-state trough and peak GFR, changes between single-dose and steady-state peak GFR, and measures of plasma renin and pro-renin. The study objective also mentions retinal blood flow, although the listed secondary outcomes do not specify a posted retinal blood flow result.

The registry record lists 13 posted secondary outcomes, while numeric comparisons are available for three secondary measures. Across those posted comparisons, the confidence intervals include zero and the unadjusted p-values do not indicate a clear separation between the groups. The estimates and uncertainty should be considered in the context of the primary finding: they do not provide a more precise answer to the primary Day 2 RPF question, because they concern different measures or measurement occasions.

These outcomes are related through their focus on renal hemodynamics and physiological responses, but they are not interchangeable. GFR and RPF measure different aspects of kidney physiology, and the captopril assessment is on a different day from the primary comparison. Steady-state measurements address a different exposure period from the primary single-dose endpoint. A pattern across outcomes may inform what was measured, but it cannot be condensed into a single treatment effect without a prespecified synthesis plan.

Unadjusted secondary results carry less weight as confirmatory evidence when multiple outcomes and comparisons are considered. Testing many questions can increase the chance of apparently notable findings, and the multiplicity strategy is not reported in the registry record. The outcome list alone does not reveal which comparisons were prespecified as primary, which were exploratory, or whether a hierarchy was used. These results are therefore best viewed as supporting descriptive context rather than independent proof of a broad effect.

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

• Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Captopril
• Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Captopril
• Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Aliskiren or Irbesartan
• Change From Baseline to Steady State Trough in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
• Change From Baseline to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
• Change From Single Dose Peak to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan
• Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan
• Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean change represent?

The primary outcome is continuous, so the registry reports a mean change for each group and a standard deviation. A mean is the arithmetic average of the measured changes in the analysis set. It offers a compact description of the group’s central tendency, but it can conceal variation among participants. The standard deviation describes that spread; it is not the uncertainty in the mean and is not a confidence interval.

For this endpoint, change is defined from a baseline RPF value to a peak value after dosing. Baseline was the median of the three recorded predose values, and peak was determined with a moving-average concept. The resulting change is tied to those measurement and summarization rules. It should not be read as a difference between a single predose reading and a single post-dose reading.

How should the group contrast be read?

The reported mean difference is the contrast between the two group summaries. Its sign depends on the order used to subtract one group from the other. The registry record gives the estimate and confidence limits, but does not state the original analysis model in the posted result. The contrast is therefore best read together with its stated estimate and interval, rather than inferring more about the analysis than the record documents.

In general, a confidence interval describes a range of values reasonably compatible with the observed data under the method used to calculate it. A 95% confidence procedure has a long-run coverage interpretation: if the same procedure were repeated under its assumptions across many comparable studies, 95% of the intervals would cover the target parameter. It is not a probability statement that this particular interval has a 95% chance of containing the true value.

Here, the interval includes zero and extends to values on either side. Zero represents no mean difference under the contrast definition. The interval’s span is therefore central to interpretation: the estimate alone should not be treated as a precise answer. The p-value is another summary of compatibility with a null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance.

Why does variability matter?

General statistical principle: when observations are highly variable, the group mean is estimated less precisely for a fixed sample size. The primary arm standard deviations are large relative to the mean contrast, and the confidence interval is correspondingly wide. This is one reason the result supports a cautious description of the data rather than a firm conclusion about the size of the difference.

Over-dispersion is a general concern when data vary more than a chosen model expects. In that situation, standard errors based on the less variable model may be too small, yielding overly narrow intervals and optimistic tests. The registry record does not identify a particular over-dispersion assessment or model for this endpoint. It would therefore be inappropriate to claim that such an assessment was performed, or that an alternative variance method was used.

What does an unadjusted p-value imply?

The primary comparison is accompanied by an unadjusted p-value. In general, an unadjusted test addresses one contrast without accounting for the possibility that many outcomes or comparisons are being examined. If many tests are conducted, the chance of finding at least one apparently notable result by chance can increase. Adjustment methods can address that issue, but the multiplicity strategy for this trial is not reported in the registry record. The p-value should consequently be read as an unadjusted summary, not as a multiplicity-controlled finding.

The registry record lists 17 outcome measures and 13 posted secondary outcomes. That breadth matters for interpretation, but it does not reveal how many analyses were prespecified, which were considered confirmatory, or whether any hierarchy was planned. Those elements are not reported in the registry record. A result’s statistical status cannot be reconstructed solely from the number of outcomes listed.

What can be inferred from the analysis population?

The stated pharmacodynamic population includes participants with available pharmacodynamic data and without major protocol deviations affecting those data. This is not automatically the same as an analysis of every randomized participant. The record does not report how many randomized participants lacked outcome data, the reasons for missing measurements, or whether any missing values were imputed. It also does not report a sensitivity analysis for missing data. Thus, the primary summaries describe the defined analysis set, and the effect of exclusions or unavailable data cannot be assessed from the registry record.

General principle: excluding participants after randomization can affect comparability if the reasons for exclusion relate to treatment or outcome. That possibility is a reason to look for participant flow and missing-data details, not evidence that bias occurred in this study. The registry record’s definition of the analysis population is available, but the additional details needed to assess the consequences of exclusions are not reported.

How do the planning projections differ from trial power?

General principle: a sample-size projection estimates how many participants a future study might need under specified assumptions to have a chosen probability of detecting a particular effect if that effect is real. The projections associated with the observed contrast are illustrative and use an assumed two-sided significance level of 0.05, equal allocation, and a normal approximation. They are not a description of the trial’s original design plan. The registry record does not report the original sample-size justification or design assumptions.

Observed power is not a useful retrospective measure of whether the study “had enough power”; it is largely determined by the observed estimate and does not resolve uncertainty. The planning projections instead show how assumptions about the effect to detect, variability, allocation and test procedure influence a future sample-size calculation. They should not be read as proof that the trial was or was not adequately designed.

The registry result also does not identify whether the contrast came from a model adjusted for baseline covariates, repeated measurements, or other factors. Although the endpoint description specifies how baseline and peak were constructed, that does not establish the statistical model used to compare groups. Model details, diagnostic checks and any prespecified decision thresholds are not reported in the registry record.

11. Confidence Intervals and Precision

The 95% confidence interval for the primary mean difference runs from -23.01 to 20.41 mL/min/1.73m^2 around an estimate of -1.3 mL/min/1.73m^2. Because the interval crosses zero, it does not rule out no mean difference. Its extension to both negative and positive values also means that the data are compatible with contrasts in either direction under the method used to calculate the interval.

The interval is broad, so the point estimate should not be mistaken for a highly precise estimate of the treatment contrast. The arm means are 37.18 and 35.88 mL/min/1.73m^2, while the arm standard deviations are 36.19 and 35.53. The standard deviations describe participant-to-participant spread, whereas the confidence interval describes uncertainty in the contrast. These quantities answer different questions.

The unadjusted p-value of 0.907 is consistent with the interval’s failure to distinguish the estimate from zero at conventional testing thresholds, but the registry record does not report the original analysis plan or its decision threshold. Neither the p-value nor the interval establishes equivalence. That would require a clinically justified equivalence margin and a suitable prespecified analysis, neither of which is reported in the registry record.

Precision is also tied to the outcome definition and analysis population. The interval concerns the single-dose Day 2 change in RPF in the pharmacodynamic analysis set. It does not quantify uncertainty for steady-state measures, other outcomes, or a broader population beyond the one represented by the recorded analysis set.

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 projections are expressed as participants per arm, not as a total across both arms and not as total events. They are illustrations based on the observed effect, rather than the original trial’s design calculation. The registry record does not report the assumptions used to choose the trial’s original enrollment.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each projection considers detecting a specified fraction of the observed effect: the full observed effect, 75% of it, or 50% of it. The figures are calculated separately for a target of 80% power and a target of 90% power.

In general, 80% power means that if the assumed effect and other planning assumptions were true, a study of that size would have an 80% chance of detecting the effect using the stated test procedure. The 90% column applies the same idea with a higher chance of detection under those assumptions. A higher target generally requires more participants. These are conditional planning probabilities, not guarantees about any particular future study.

The observed primary contrast is small relative to the variability in the group summaries. Consequently, planning around that small observed contrast yields large participant projections. The same logic explains why detecting a smaller effect requires more participants: a smaller signal is harder to distinguish from random variation. Projections can change substantially when the assumed effect, variability, significance level, allocation or analysis method changes.

These projections are not observed power. They are not evidence that the completed trial had a particular probability of success, and they should not be used to judge the original design, whose assumptions are not reported in the registry record. They are best read as conditional illustrations of the sample size that would be needed for future planning 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 = -1.300; pooled standard deviation σ = 35.878.
2. n = 2 × (1.96 + 0.842)² × 35.878² / -1.300² = 11,956.6, rounded up to 11,957 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 <- -1.3                      # observed difference in means
sigma <- 35.8780138803697                     # 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(660309)
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 = 11,957 (80% power), 16,007 (90% power)
 75% of observed effect: n per arm = 21,257 (80% power), 28,456 (90% power)
 50% of observed effect: n per arm = 47,827 (80% power), 64,026 (90% power)
power.t.test: 11957.6 
Simulated power at n = 11,957 per arm: 0.804 (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. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and multiple secondary outcomes, but does not report a multiplicity plan. It is not clear whether the study used a hierarchy of tests, adjusted p-values, or another method to control the interpretation of multiple comparisons. The posted primary p-value is explicitly unadjusted, and the secondary comparisons are also presented with unadjusted p-values.

General statistical principle: when several hypotheses are tested, each test can produce an apparently unusual result by chance even if none of the underlying effects is real. The chance of at least one such result grows as the number of tests grows, unless the analysis plan accounts for multiplicity. This does not mean that any particular reported result is false; it means that isolated p-values should be interpreted in light of the number and role of the analyses.

The registry lists 17 outcome measures and 13 posted secondary outcomes. It does not report which secondary outcomes were designated as confirmatory, whether all were analyzed, how tests were grouped, or whether outcomes were selected for posting based on a prespecified plan. It also lists no reported analyses. The original statistical analysis plan is not reported in the registry record, so the planned handling of multiplicity cannot be reconstructed.

Missing-data information is similarly limited. The primary pharmacodynamic analysis set required available data and excluded major protocol deviations affecting pharmacodynamic data. The registry record does not report the number or reasons for missing measurements, the extent of exclusions due to deviations, any imputation method, or sensitivity analyses. Without those details, readers cannot assess how incomplete observations may have influenced the estimates.

The result should therefore be read as a posted summary in a setting where multiplicity and missing-data procedures are not fully documented. This is a limitation in what can be evaluated from the registry record; it is not evidence that a particular adjustment or missing-data method was omitted from the study conduct.

15. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry safety groups report zero participants with serious adverse events among those at risk in each listed group: 45 for captopril 25 mg, 22 for aliskiren 300 mg, and 21 for irbesartan 300 mg. The record lists no serious adverse event terms. These counts describe the registry’s reported groups and should be read within their respective exposure periods and group definitions.

Other adverse events affected 2 participants in the captopril group, 5 in the aliskiren group, and 5 in the irbesartan group. These are counts of participants affected, not counts of all event episodes. The record does not provide event-level descriptions in the safety summary, so the figures alone do not indicate the nature, severity, timing or relatedness of those events.

Deaths are not reported in the registry record. The absence of reported serious adverse events in these groups does not establish that an intervention is safe, particularly because the study was small and focused on physiological outcomes. The safety counts are descriptive, not a powered comparison of adverse-event risk.

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

The primary result describes a short-term physiological comparison: mean change in RPF after a single Day 2 dose of aliskiren or irbesartan in the pharmacodynamic analysis set. The posted means were 37.18 mL/min/1.73m^2 and 35.88 mL/min/1.73m^2, with a reported difference of -1.3 mL/min/1.73m^2. The confidence interval is broad and includes zero, so the estimate does not precisely establish the direction or size of the group contrast.

This does not demonstrate that the treatments are equivalent. Equivalence is a specific statistical claim that depends on a clinically justified margin and a design capable of assessing whether the confidence interval stays within that margin. Neither an equivalence margin nor an equivalence analysis is reported in the registry record. Likewise, the result does not establish that both groups have the same response or that either has no response.

The endpoint is not a clinical event or a long-term outcome. It is based on a short observation window after dosing and a particular way of measuring baseline and peak RPF. The result cannot establish effects on long-term kidney function, complications of diabetes, quality of life, or other outcomes not reported in the primary result. The study objective mentions retinal blood flow, but the primary result does not answer that question.

The trial description includes a 14-day dosing regimen and steady-state outcomes, but the primary comparison concerns the response after a single dose. It should not be generalized to the full regimen without considering the separate steady-state evidence. Nor should a result in this pharmacodynamic analysis set automatically be generalized beyond the participants and data represented in that set.

The posted summaries are useful for understanding the measured response and the amount of uncertainty around the mean contrast. They do not justify medical advice or a treatment choice. Their meaning is limited by the size of the analysis groups, the open-label design, the absence of reported multiplicity and missing-data details, and the lack of a reported original statistical plan.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate and its uncertainty need to be read together. The reported mean difference is close to zero, but the confidence interval is broad. Looking only at the point estimate could suggest that the groups are nearly alike; looking only at the p-value could encourage an incorrect conclusion that there is no difference. The interval makes the remaining uncertainty visible.

It also highlights the distinction between a physiological endpoint and a patient-relevant outcome. RPF is a defined continuous measure, assessed through PAH clearance and summarized using specified baseline and peak rules. That makes the endpoint interpretable as a measure of renal hemodynamics, while keeping its scope narrower than a claim about long-term health outcomes.

The study is also a reminder that registry outcome lists and posted results do not substitute for a full statistical analysis plan. The record provides the endpoint definition and numerical summaries, but does not report the original sample-size justification, model details, multiplicity strategy or missing-data methods. Those omissions limit the ability to assess whether the posted analyses match the planned analyses.

Finally, the planning projections show how a small observed contrast combined with substantial variability can translate into large future sample-size requirements under stated assumptions. Such projections are conditional tools for design planning, not retrospective proof of a trial’s adequacy. Keeping that distinction clear helps prevent observed estimates from being mistaken for reliable planning targets.

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.

The primary analysis groups are small: 22 participants for aliskiren and 20 for irbesartan. The confidence interval is wide, leaving substantial uncertainty about the size and direction of the mean contrast. The overall enrollment is 45, but the primary result uses a defined pharmacodynamic analysis set rather than simply reporting every enrolled participant.

The study was open-label with no masking. The endpoint is an instrument-based physiological measure, but the registry record does not report whether outcome assessment was masked or whether assessors could have known treatment assignments. Randomization is recorded, but the sequence-generation and allocation-concealment methods are not reported.

The primary endpoint concerns a single-dose response on Day 2. It does not directly address sustained effects or clinical outcomes. Although the study description includes 14 days of dosing and outcomes at steady state, these are separate measurements and should not be conflated with the primary result. The registry record does not report a threshold for a clinically important RPF change.

Important analysis details are unavailable: the original sample-size justification, the statistical model, the multiplicity strategy, missing-data handling, and sensitivity analyses are not reported in the registry record. The primary population definition excludes major protocol deviations affecting pharmacodynamic data, but participant flow and the impact of exclusions cannot be evaluated from the reported information. These limitations constrain interpretation; they do not establish that the study’s conduct was biased.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus — NCT00660309.
• Registry record last updated 2012-08-29; status last verified 2012-08.
• Results first posted 2012-08-29.
• 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

NCT00660309 is a completed Phase 4, randomized, open-label, parallel-group study sponsored by Novartis. It enrolled 45 people with type 2 diabetes mellitus. Participants received 25 mg captopril on Day 1, followed from Day 2 by 14 days of once-daily aliskiren 300 mg or irbesartan 300 mg.

The primary endpoint was change from baseline in RPF after a single dose on Day 2. The posted mean difference was -1.3 mL/min/1.73m^2, with a 95% confidence interval from -23.01 to 20.41 and an unadjusted p-value of 0.907. The interval is broad and includes zero, so the result does not establish a precise group difference or equivalence.

The registry record does not report the original sample-size justification, full statistical analysis plan, multiplicity approach, or missing-data methods. The findings describe the posted physiological outcome and should not be interpreted as evidence about long-term clinical outcomes.