This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effects of Dapagliflozin in Non-diabetic Patients With Proteinuria (NCT03190694), a randomized phase 2 study. The primary outcome is Change in 24-hr Proteinuria With Dapagliflozin for Six Weeks Relative to Placebo in Patients With Non-diabetic Kidney Disease and Proteinuria 500 mg/Day on Stable Angiotensin-converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Treatment..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03190694 |
| Phase | Phase 2 |
| Condition | Chronic Kidney Diseases, Proteinuria |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 53 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hiddo Lambers Heerspink |
| Results posted | Yes |
2. Clinical Question
The clinical question concerns whether six weeks of dapagliflozin is associated with a different change in 24-hour proteinuria than six weeks of matching placebo in patients with non-diabetic kidney disease and proteinuria. The primary outcome description specifies proteinuria of 500 mg/day and stable treatment with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker. The registry summary frames the study hypothesis as whether dapagliflozin lowers proteinuria in patients with non-diabetic chronic kidney disease.
Population
Patients with non-diabetic kidney disease and proteinuria. The primary outcome description specifies proteinuria of 500 mg/day while receiving stable angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment.
Intervention
Dapagliflozin 10 mg tablet, taken for six weeks in one treatment period.
Comparator
A matching placebo tablet, taken for six weeks in the other treatment period.
Primary question
What change in 24-hour proteinuria is reported after six weeks of dapagliflozin relative to placebo?
The crossover design means the treatment periods were assigned in different orders: one sequence began with dapagliflozin and then received placebo, while the other began with placebo and then received dapagliflozin. A washout period separated the treatment periods. In general, a crossover trial can use within-participant comparisons, which may account for stable differences between people. The registry record does not report the specific analysis used to make the treatment comparison, so the posted arm summaries alone should not be read as a complete paired treatment effect.
The stated question is about a biomarker outcome over the listed treatment period. It is not a question about long-term kidney outcomes or about whether dapagliflozin changes the course of kidney disease. Those outcomes are not established by the primary outcome as described.
3. Trial Design
The registry identifies this as a completed, randomized, double-blind, Phase 2 crossover study. Its title describes a six-week crossover trial, and the treatment descriptions specify six weeks of dapagliflozin, a six-week washout period, and six weeks of placebo. Participants followed one of two orders: dapagliflozin followed by placebo, or placebo followed by dapagliflozin. The placebo was described as matching dapagliflozin.
The registry enrollment is 53. The arm summaries report 53 for the dapagliflozin period and 52 for the placebo period. These entries should not be added to estimate the number of participants, because the design is crossover and the same participant may contribute observations in both treatment periods. The registry record does not explain the difference between the enrollment entry and the arm summary entries.
Randomization indicates that treatment order was assigned rather than chosen by the participants or investigators. Double masking indicates that the study was recorded as double-blind, though the registry record does not describe which roles were masked or how masking was maintained. The record names dapagliflozin 10 mg and matching placebo as the interventions.
The listed study dates are a start date of 2017-11-12 and a primary completion date of 2019-11-01. The registry status is completed. The sponsor is identified in the registry record as Hiddo Lambers Heerspink. These administrative details describe the registered study, but they do not provide further information about conduct, adherence, or the analysis population.
A crossover design can be efficient when an outcome can be measured during separate treatment periods and the effect is not expected to persist in a way that contaminates the next period. Those are general design considerations, not reported findings about this trial. The registry record does not report whether period effects or carryover were assessed, or how the washout period was chosen. It also does not provide detail on treatment adherence, withdrawals, or the number of participants contributing complete observations to both periods.
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.
Period 1
| Stage | Dapagliflozin 10mg Tablet, Then Placebo | Placebo, Then Dapagliflozin |
|---|---|---|
| STARTED | 27 | 26 |
| COMPLETED | 26 | 26 |
| NOT COMPLETED | 1 | 0 |
Period 2 (After 6 Weeks Wash-out)
| Stage | Dapagliflozin 10mg Tablet, Then Placebo | Placebo, Then Dapagliflozin |
|---|---|---|
| STARTED | 26 | 26 |
| COMPLETED | 26 | 26 |
| NOT COMPLETED | 0 | 0 |
Wash-out and Follow-up
| Stage | Dapagliflozin 10mg Tablet, Then Placebo | Placebo, Then Dapagliflozin |
|---|---|---|
| STARTED | 26 | 26 |
| COMPLETED | 24 | 26 |
| NOT COMPLETED | 2 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Dapagliflozin 10mg Tablet | Placebo Matching Dapagliflozin Tablet | Total |
|---|---|---|---|---|
| Participants analysed | 27 | 26 | 53 | |
| Age, Continuous | years | 52 (SD 10) | 51 (SD 16) | 51 (SD 13) |
| Sex: Female, Male: Female | Participants | 9 | 8 | 17 |
| Sex: Female, Male: Male | Participants | 18 | 18 | 36 |
| Race/Ethnicity, Customized: Asia | Participants | 11 | 6 | 17 |
| Race/Ethnicity, Customized: Hispanic | Participants | 2 | 0 | 2 |
| Race/Ethnicity, Customized: Caucasian | Participants | 12 | 17 | 29 |
| Race/Ethnicity, Customized: Other | Participants | 2 | 3 | 5 |
| Proteinuria | mg/24h | 1170 (730 to 1690) | 1105 (720 to 1530) | 1110 (730 to 1560) |
| mGFR | ml/min/1.73m2 | 58.9 (SD 20.7) | 57.8 (SD 25.5) | 58.3 (SD 23.0) |
6. Primary Endpoint
The registry lists the primary outcome as Change in 24-hr Proteinuria With Dapagliflozin for Six Weeks Relative to Placebo in Patients With Non-diabetic Kidney Disease and Proteinuria 500 mg/Day on Stable Angiotensin-converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Treatment., measured over 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | % change from baseline |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the change in 24-hour proteinuria, expressed as percentage change from baseline, after six weeks. Proteinuria refers to protein measured in urine; a 24-hour collection is intended to characterize the amount excreted over a full day. The outcome is continuous, and the registry states that its reported parameter is a mean with a 95% confidence interval.
Proteinuria is relevant to this study because the registered hypothesis concerns whether dapagliflozin lowers proteinuria in patients with non-diabetic chronic kidney disease. Measuring change from baseline focuses on the difference between a participant’s starting level and the level after the treatment period, rather than on the follow-up measurement alone. Expressing change as a percentage places the change relative to the baseline value.
As a general statistical point, a continuous endpoint preserves information across the range of measured values rather than reducing them to categories. A mean describes the central value of the reported changes, while a confidence interval communicates uncertainty around that estimate. Neither one, by itself, establishes the size or precision of the treatment contrast. For a crossover comparison, the relevant treatment contrast depends on how the observations across periods and treatment orders are handled.
The primary outcome description calls the analysis “bioequivalence,” but the registry record does not state the equivalence margin or give a separate treatment-comparison estimate. The recorded endpoint is therefore clear as a measure, while the specific decision rule for interpreting equivalence is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry posts mean percentage changes from baseline for each treatment period, together with 95% confidence intervals. For dapagliflozin, the reported mean is -15.04, with a 95% confidence interval from -25.7 to -2.76. For placebo, the reported mean is -15.8, with a 95% confidence interval from -26.43 to -3.54. Both posted means are negative, and both reported confidence intervals contain only negative values. These are summaries for the treatment groups or periods; they are not themselves a direct estimate of the treatment-versus-placebo difference.
The primary outcome is described as change with dapagliflozin relative to placebo, but the registry record does not post a treatment contrast, its confidence interval, or a p-value. The record also lists zero analyses. As a result, the two means cannot establish whether the treatments differ, how precisely a difference was estimated, or whether a prespecified criterion for bioequivalence was met. The label “bioequivalence” does not supply the missing decision margin or analysis.
A confidence interval gives a range of values compatible with the estimate under the assumptions of the analysis. In general, it expresses uncertainty rather than certifying that the true treatment effect lies in the range or assigning a probability to a particular value. Here the intervals describe the posted mean changes, not a treatment contrast. They should not be treated as if they were the interval for the difference between dapagliflozin and placebo.
The two arm-level summaries are not enough to reconstruct the paired crossover comparison. In general, the precision of a within-participant contrast depends on how each participant’s measurements relate across treatment periods, as well as on the analysis model. The registry record does not report that relationship or the model used. It also does not report results by treatment sequence or period. Consequently, no unadjusted re-calculation of a valid crossover treatment effect is available from the posted summaries alone.
The trial’s enrollment and arm summary counts describe different registry entries. The enrollment is listed as 53, while the treatment summaries report 53 for dapagliflozin and 52 for placebo. In a crossover study, treatment-period summaries need not represent separate groups of participants, so those numbers should not be summed or interpreted as independent samples. The record does not explain why the listed counts differ.
The registered primary outcome is a short-term measure, assessed at six weeks. It does not directly report longer-term kidney function, clinical events, or durability of a response. The secondary outcomes include glomerular filtration rate, blood pressure, body weight, and several urine ratios, but the registry record does not post analyses for them. The interpretation is therefore limited to the available endpoint summaries and safety counts, not a broader evaluation of kidney outcomes.
Overall, the posted values describe negative mean changes within both treatment periods. They do not provide the direct estimate needed to judge the comparative effect, and they do not establish whether a bioequivalence criterion was satisfied. This is a limitation of what the registry record reports, rather than evidence for or against a treatment difference.
9. Statistical Methods Explained
The registry describes the primary measure as a mean of a continuous outcome and reports a 95% confidence interval for each treatment summary. This means the posted values summarize percentage change from baseline in 24-hour proteinuria, rather than giving counts of participants who crossed a threshold. The registry record does not report the statistical model or the procedure used to calculate the interval.
What does a mean describe?
In general, a mean is the arithmetic average of the observations included in an analysis. It gives a central summary but can conceal variation between participants and can be affected by unusually high or low observations. For clinical measurements, the mean is most informative when considered alongside an uncertainty measure and with an understanding of which observations were included. The registry reports confidence intervals, but it does not report a standard deviation, standard error, or individual participant values for this endpoint.
Change from baseline is a way to express how an outcome differs from its starting measurement. Percentage change scales that difference relative to baseline, whereas an absolute change would retain the original measurement units. The endpoint is explicitly labelled as percentage change from baseline, so the posted values should be interpreted on that scale. The record does not give the specific calculation convention used for individual percentage changes or explain how missing baseline or follow-up measurements were handled.
What does a confidence interval add?
As a general explanation, a confidence interval reflects sampling uncertainty under a statistical procedure and its assumptions. A narrower interval indicates greater precision for the estimate to which it applies; a wider interval indicates less precision. A confidence interval is not a direct measure of how much individual participants varied, and it does not resolve bias from missing data, measurement problems, or a model that does not fit the design.
The posted 95% confidence intervals accompany the treatment-specific mean changes. They do not represent the interval for the difference between dapagliflozin and placebo. The distinction matters because the scientific question is comparative. In a crossover design, a treatment comparison generally uses information about both treatment periods for each participant, and the relationship between those repeated measurements contributes to the uncertainty of the contrast. The registry record does not provide a paired contrast or the covariance information needed to reconstruct one from the arm summaries.
Why does the crossover design matter?
In general, a crossover trial assigns treatment order and observes participants during more than one treatment period. A within-participant comparison can reduce the influence of stable characteristics that differ between people, because each participant may contribute information under each treatment. This benefit relies on appropriate handling of period, sequence, and possible carryover effects. A period effect occurs when outcomes differ because of when a measurement is taken, apart from the treatment itself. Carryover refers to a treatment effect that persists into a later period and can affect the next treatment observation.
The record states that the trial was randomized, double blind, and crossover, with a six-week washout between treatment periods. It does not report the crossover analysis model, whether treatment order or period was included in that model, how carryover was assessed, or whether the washout was considered sufficient. Those details should not be assumed from the design label alone. The record also does not specify whether the published means are period-specific summaries, estimates adjusted for other design features, or based on a particular analysis population.
What does the “bioequivalence” description establish?
The primary endpoint description includes the term “bioequivalence.” In general, an equivalence analysis asks whether the treatment difference is sufficiently close to a prespecified margin, rather than merely whether a conventional test detects a difference. Interpretation requires a defined margin and a confidence interval for the relevant contrast. The registry record does not report an equivalence margin or a treatment-contrast interval. The word in the endpoint description therefore does not, by itself, show that an equivalence analysis was completed or that its criterion was met.
How should planning calculations be understood?
The registry record includes assumptions for planning illustrations based on the observed effect: a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. These are planning assumptions, not evidence about the trial’s observed precision or the probability that a result is true. Sample-size calculations under such assumptions are illustrations of what a future design might require under a specified scenario. The registry record does not report the trial’s own sample-size justification or provide a basis for describing the study’s observed power.
In general, power is a design property defined in relation to a specified effect, variability, significance threshold, and analysis. It is not a post hoc measure of whether the observed result is convincing. Planning calculations that use an effect estimated in the same study also inherit uncertainty in that estimate. The registry record does not report a prespecified target effect or variance assumptions for the original design, so no such rationale should be inferred.
Which statistical details remain unavailable?
The registry lists 11 outcome measures and 10 posted secondary outcomes, while listing zero analyses. It does not describe a statistical analysis plan, a multiplicity strategy, an imputation method, or rules for defining analysis populations. General statistical practice may address these issues in different ways, but the registry record does not identify which approach was used. Without those details, it is not possible to determine how the posted summaries relate to a prespecified analysis or how uncertainty from multiple outcomes was handled.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 secondary outcomes in addition to the primary endpoint description, and it lists 11 outcome measures overall. These include glomerular filtration rate using iohexol clearance, systolic and diastolic blood pressure, body weight, several urine ratios, and safety measures. The record lists zero analyses, so no secondary treatment comparisons or corresponding uncertainty estimates are posted in the information available for interpretation.
When a study examines multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately. General approaches include prioritizing a primary outcome, adjusting inference for multiple comparisons, or clearly treating secondary findings as exploratory. The registry record does not report which approach was planned or used. No multiplicity adjustment should be assumed.
The registry record also does not report how missing measurements were handled, the number of participants with complete paired data, or the analysis population for the primary endpoint. It does not specify whether all randomized participants were included in an analysis, whether participants with incomplete periods were excluded, or whether any imputation was used. These matters are important in crossover studies because a participant may have measurements for one period but not the other, and the treatment contrast can depend on which paired observations are available.
The posted treatment summaries include different counts for the dapagliflozin and placebo entries, while the registry enrollment is separately listed. The record does not explain the count difference or the role of missing observations. Without participant flow and analysis-population details, the precision and representativeness of the reported summaries cannot be fully assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Dapagliflozin 10mg Tablet | 1 | 53 | 1.9% |
| Placebo Matching Dapagliflozin Tablet | 1 | 52 | 1.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dapagliflozin 10mg Tablet | 0 of 53 |
| Placebo Matching Dapagliflozin Tablet | 0 of 52 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dapagliflozin 10mg Tablet | 17 of 53 |
| Placebo Matching Dapagliflozin Tablet | 13 of 52 |
Most frequent serious adverse event terms
| Event term | Organ system | Dapagliflozin 10mg Tablet | Placebo Matching Dapagliflozin Tablet |
|---|---|---|---|
| Cellulitis | Skin and subcutaneous tissue disorders | 0 of 53 | 1 of 52 |
| Colon Cancer | Gastrointestinal disorders | 1 of 53 | 0 of 52 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dapagliflozin 10mg Tablet | Placebo Matching Dapagliflozin Tablet |
|---|---|---|---|
| Any adverse event | General disorders | 17 of 53 | 13 of 52 |
Serious events with the highest arm-level rate: cellulitis (1.9%), colon cancer (1.9%).
The posted safety figures report one serious adverse event among 53 at risk in the dapagliflozin group and one among 52 at risk in the placebo group. Deaths are reported as 0 in each group. These counts describe what the registry records; they do not, on their own, establish whether the treatments differ in safety. With few serious events, the counts provide limited information about the range of possible differences.
The record also reports 17 participants with other adverse events among 53 at risk in the dapagliflozin group and 13 among 52 at risk in the placebo group. The specific definitions and collection procedures for “other” adverse events are not reported in the registry record. The secondary outcome description refers to hypoglycemic events and/or serious adverse events, but the posted group summaries do not separate that combined description into further detailed outcome results.
Cellulitis and colon cancer are listed among the top serious adverse event terms, each with a reported value of 1.9%. The record does not identify the treatment group for those terms in the listed summary, so they should not be attributed to one group. Adverse-event counts are descriptive and do not establish causation. The registry record does not provide event timing, duration, severity beyond the serious classification, or a statistical comparison.
12. What the Result Does, and Does Not, Mean
The posted primary summaries show mean percentage changes from baseline in 24-hour proteinuria for the dapagliflozin and placebo treatment periods. Both means are negative, and each has a reported 95% confidence interval. These numbers describe changes within the treatment summaries; they are not a direct estimate of the difference between treatments. The registry record does not provide the comparative estimate, its confidence interval, or a p-value.
That distinction limits what can be concluded. A negative mean in each period does not establish that dapagliflozin changed proteinuria more or less than placebo. Nor does it show that the two treatments are equivalent. The primary outcome description uses the term “bioequivalence,” but the registry record does not report an equivalence margin or the treatment contrast needed to assess such a criterion.
The outcome is a short-term measure assessed at six weeks. It does not establish whether any observed change persists, whether it corresponds to a change in longer-term kidney function, or whether it affects clinical outcomes. The registry lists other outcomes, including glomerular filtration rate, blood pressure, body weight, and urine ratios, but does not post analyses for them.
Similarly, the safety counts are not a comprehensive basis for comparing risk. The registry reports serious and other adverse-event counts and deaths, but does not provide detailed event timing, a formal statistical comparison, or a complete description of ascertainment. A small number of serious events cannot rule out effects that the available data may estimate imprecisely.
The results should therefore be read as registry-posted summaries, not as a complete report of the trial’s comparative efficacy or safety analysis. The record establishes the design, endpoint description, group-level means and confidence intervals, and selected adverse-event counts. It does not report enough statistical detail to evaluate the primary treatment contrast or to determine whether a prespecified equivalence conclusion was reached.
13. Why This Trial Matters Statistically
This trial is statistically notable because it uses a randomized crossover design for a continuous biomarker endpoint. In general, crossover designs can compare treatments within participants, potentially reducing the effect of stable between-person differences. That advantage depends on an analysis that respects repeated measurements, treatment order, period effects, and possible carryover. The registry record identifies the crossover structure and washout period but does not report how these features were handled analytically.
The primary outcome is also labelled as “bioequivalence,” which highlights the difference between testing for a detectable difference and evaluating whether treatments are sufficiently similar within a defined margin. An equivalence interpretation requires a prespecified margin and a treatment contrast with an appropriate confidence interval. Neither is reported in the registry record. Thus, the endpoint label draws attention to an important statistical question that the posted summaries do not resolve.
The record provides treatment-specific means and confidence intervals, but not the direct comparative estimate. This illustrates why group-level summaries may be inadequate for interpreting a crossover trial: the treatment comparison relies on the relationship between the observations from the same participant across periods. Without that paired analysis, the reported summaries do not answer the comparative question precisely.
The registry also lists multiple secondary outcomes but no analyses. This makes transparent reporting of analysis plans and missing-data procedures especially important: readers need to distinguish a prespecified primary test from exploratory analyses and understand which participants contributed to each outcome. The record does not provide that context. The statistical significance of the study is therefore less about a definitive treatment conclusion and more about the limits of interpreting incomplete comparative reporting.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation is that the registry record does not report the primary treatment contrast, even though the primary outcome is described as a comparison of dapagliflozin relative to placebo. The record provides separate means and confidence intervals, but not a paired crossover estimate, its uncertainty, or a p-value. It also lists zero analyses. These omissions prevent a direct assessment of the stated comparative question from the posted results.
The record does not report whether the primary analysis accounted for treatment sequence, period, or carryover, nor whether the washout period was adequate for the measured outcome. These are relevant considerations in a crossover study, but no trial-specific conclusion about them can be drawn from the registry information. The analysis population, participant flow, missing-data approach, and number of complete paired observations are also not reported.
The endpoint description calls the analysis “bioequivalence,” but the equivalence margin and the confidence interval for the treatment contrast are not reported in the registry record. Without these, the label cannot be interpreted as evidence that equivalence was tested or established. The record also does not state a statistical analysis plan or the method for handling multiple outcomes.
The registry’s enrollment entry is 53, while treatment summaries list 53 for dapagliflozin and 52 for placebo. The record does not explain this difference. Because the study is crossover, the treatment summaries should not be treated as independent groups or combined to infer participant totals.
Finally, the posted primary endpoint concerns a six-week change in proteinuria, and the secondary outcome analyses are not reported. The record therefore offers limited information about longer-term outcomes, other measured endpoints, and the completeness of safety assessment. These are limitations of the available registry record, not proof that the trial did not collect or analyze those data.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effects of Dapagliflozin in Non-diabetic Patients With Proteinuria — NCT03190694.
- Registry record last updated 2024-06-17; status last verified 2024-01.
- Results first posted 2024-06-17.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed, randomized, double-blind, Phase 2 crossover trial of dapagliflozin 10 mg and matching placebo in non-diabetic patients with proteinuria. The treatment periods were six weeks each, separated by a six-week washout. The primary endpoint was percentage change from baseline in 24-hour proteinuria after six weeks.
The posted mean changes are -15.04 for dapagliflozin and -15.8 for placebo, with respective 95% confidence intervals of -25.7 to -2.76 and -26.43 to -3.54. The record does not post a direct treatment contrast or its statistical analysis. It lists 10 secondary outcomes and zero analyses.
Safety summaries report one serious adverse event in each treatment entry and 0 deaths in each. The registry record does not report enough detail to determine the comparative treatment effect, assess an equivalence criterion, or fully evaluate missing data, multiplicity, and crossover-specific analysis choices.