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 Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease (NCT04595370), a randomized phase 2 study. The primary outcome is Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04595370 |
| Phase | Phase 2 |
| Condition | Heart Failure, Chronic Kidney Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 153 |
| Arms in the primary outcome | 6 |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Participants had heart failure with left ventricular ejection fraction below 60% and chronic kidney disease with estimated glomerular filtration rate from 20 to 60 mL/min/1.73 m². The planned population included at least 20% with estimated glomerular filtration rate from 20 to below 30 mL/min/1.73 m², and no more than 35% with estimated glomerular filtration rate at least 45 mL/min/1.73 m². The registry record reports enrollment of 153 participants.
Intervention
The primary analysis included three dose groups receiving AZD9977 at 15 mg, 50 mg, or 150 mg, each with dapagliflozin 10 mg once daily. Treatment was described for 12 weeks.
Comparator
The active comparator for the primary analysis was dapagliflozin 10 mg once daily alone. AZD9977 150 mg monotherapy and placebo were among the original arms, but those arms were removed early and were not included in the revised mixed-effects analysis.
Primary question
The primary question was whether the percent change from baseline in urinary albumin-to-creatinine ratio at Week 12 differed across the retained AZD9977-plus-dapagliflozin dose groups and dapagliflozin alone. The endpoint also supported assessment of a dose-response relationship. The registry reports an omnibus F-test for the four retained arms rather than a set of arm-by-arm comparisons.
Urinary albumin-to-creatinine ratio, abbreviated UACR, combines urine albumin and urine creatinine measurements into a ratio. The endpoint is expressed as percent change from baseline, so negative values indicate a decrease from baseline and positive values indicate an increase. This is a measure of change in a laboratory marker, not a direct measure of how participants feel or function.
3. Trial Design
This was a randomized, parallel-group Phase 2b study sponsored by AstraZeneca. The registry describes the study as double-blind in its official title and records quadruple masking. The study status is completed. The recorded start date is 2021-01-26, and the primary completion date is 2023-09-22.
The registry lists four treatment arms that remained in the primary analysis: AZD9977 15 mg plus dapagliflozin 10 mg, AZD9977 50 mg plus dapagliflozin 10 mg, AZD9977 150 mg plus dapagliflozin 10 mg, and dapagliflozin 10 mg alone. Each regimen was described as once-daily oral treatment for 12 weeks. The posted outcome counts analyzed were 32, 23, 25, and 28, respectively. The outcome record also lists AZD9977 150 mg alone and placebo, but explains that these arms were removed early and were not included in the formal MMRM analysis.
The primary outcome was percent change from baseline in UACR at Week 12, based on urine samples. The registry says the Week 12 value was calculated as the average of UACR values at Week 12 and analyzed using a mixed-effects model for repeated measures. The full analysis set included randomized participants whether or not they received study intervention; for this outcome, the reported analyzed count refers to participants evaluated for the measure.
Other posted outcomes addressed the UACR dose-response relationship, adverse events, serum potassium, and estimated glomerular filtration rate. The registry lists six secondary outcomes and seven outcome measures in total. It does not report a detailed recruitment rationale or the reasoning behind the original enrollment target in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Participants who signed the Informed Consent Form (ICF) were enrolled into study. The study included an optional pre-screening visit.
Overall Study
| Stage | AZD9977 15 mg + Dapagliflozin 10 mg | AZD9977 50 mg + Dapagliflozin 10 mg | AZD9977 150 mg + Dapagliflozin 10 mg | AZD9977 150 mg | Dapagliflozin 10 mg | Placebo |
|---|---|---|---|---|---|---|
| STARTED | 35 | 33 | 36 | 7 | 35 | 7 |
| COMPLETED | 33 | 25 | 27 | 6 | 29 | 6 |
| NOT COMPLETED | 2 | 8 | 9 | 1 | 6 | 1 |
Reasons for not completing this period:
| Reason | AZD9977 15 mg + Dapagliflozin 10 mg | AZD9977 50 mg + Dapagliflozin 10 mg | AZD9977 150 mg + Dapagliflozin 10 mg | AZD9977 150 mg | Dapagliflozin 10 mg | Placebo |
|---|---|---|---|---|---|---|
| Subjects randomised, not treated, Protocol Deviation | 1 | 0 | 0 | 0 | 0 | 0 |
| Subjects randomised, not treated, Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Adverse Event | 0 | 4 | 3 | 1 | 1 | 1 |
| Withdrawal of Consent | 1 | 1 | 1 | 0 | 0 | 0 |
| Death | 0 | 1 | 0 | 0 | 1 | 0 |
| Protocol-Specified Withdrawal Criterion Met | 0 | 0 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 1 | 0 | 2 | 0 |
| Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Participants discontinued study treatment due to other reasons | 0 | 2 | 2 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set included all participants who were randomized and either received or did not receive any study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.
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: Total 153 participants were randomized but 9 participants were excluded from full analysis set (FAS) due to good clinical practice (GCP) misconduct at site. Hence, 144 participants were included in FAS. FAS included all participants who were randomized and either received or did not receive any study intervention.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | AZD9977 15 mg + Dapagliflozin 10 mg | AZD9977 50 mg + Dapagliflozin 10 mg | AZD9977 150 mg + Dapagliflozin 10 mg | AZD9977 150 mg | Dapagliflozin 10 mg | Placebo |
|---|---|---|---|---|---|---|---|
| Participants analysed | 34 | 31 | 35 | 6 | 33 | 5 | |
| Age, Continuous | Years | 70.9 (SD 7.1) | 72.4 (SD 8.4) | 73.7 (SD 8.1) | 77.0 (SD 8.7) | 72.2 (SD 9.4) | 77.2 (SD 5.8) |
| Sex: Female, Male: Female | Participants | 11 | 5 | 8 | 1 | 10 | 1 |
| Sex: Female, Male: Male | Participants | 23 | 26 | 27 | 5 | 23 | 4 |
| Race/Ethnicity, Customized: Asian | Participants | 4 | 3 | 7 | 0 | 3 | 0 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 | 1 | 1 | 0 | 2 | 1 |
| Race/Ethnicity, Customized: White | Participants | 30 | 27 | 27 | 6 | 28 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12, measured over Baseline (Day 1) to Week 12.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Percent change from baseline |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is percent change from baseline in urinary albumin-to-creatinine ratio at Week 12. UACR is calculated from urine albumin and urine creatinine, with the registry expressing the ratio in milligrams per gram. The endpoint therefore captures change in a urine laboratory measure over the treatment period. A negative percent change represents a lower UACR relative to baseline; a positive percent change represents a higher value.
UACR is used as a marker of albumin in urine in the setting of kidney disease. As general statistical and clinical context, measuring a continuous laboratory outcome can provide more detail about the degree of change than reducing results to categories such as improved or not improved. The measure does not, on its own, describe symptoms, daily function, or longer-term clinical events.
The posted mean percent changes were -56.39 for AZD9977 15 mg plus dapagliflozin, -42.09 for AZD9977 50 mg plus dapagliflozin, -58.05 for AZD9977 150 mg plus dapagliflozin, and -34.32 for dapagliflozin alone. Their respective 95% confidence intervals were -71.53 to -33.21, -64.17 to -6.376, -73.56 to -33.43, and -58.2 to 3.22. These are estimates of group-level change; the intervals convey uncertainty around the estimates and should not be read as individual participant ranges.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
Across the four arms retained for the primary MMRM analysis, the reported mean percent changes in UACR were negative. The estimates were -56.39 for AZD9977 15 mg plus dapagliflozin, -42.09 for AZD9977 50 mg plus dapagliflozin, -58.05 for AZD9977 150 mg plus dapagliflozin, and -34.32 for dapagliflozin alone. These figures describe within-arm change from baseline. They do not by themselves quantify the adjusted difference between each combination arm and dapagliflozin alone.
The reported 95% confidence intervals were -71.53 to -33.21, -64.17 to -6.376, -73.56 to -33.43, and -58.2 to 3.22, in the same arm order. A confidence interval is a range of values compatible with the data and the model under its assumptions; it is not a range containing a fixed proportion of individual outcomes. The intervals for the combination arms and comparator overlap. Comparing overlap by eye is not a substitute for the model-based test or for a direct contrast with its own uncertainty interval.
The registry reports an F-test statistic of 1.07 and a p-value for the overall analysis. The test covers the four retained arms specified in the revised analysis. It is an omnibus test: it evaluates evidence of differences across the group means as a whole, rather than separately testing each dose against dapagliflozin. Since the numerical p-value is not reproduced in this interpretation, the statistic should be read alongside the sponsor's formal analysis record rather than treated as a standalone conclusion.
The displayed estimates do not form a steadily ordered sequence across the three AZD9977 doses. The 50 mg estimate is less negative than the 15 mg and 150 mg estimates, while the 150 mg and 15 mg estimates are similar in direction. This pattern alone cannot establish or rule out a dose-response relationship. The uncertainty intervals are broad, and a pattern in point estimates does not replace a prespecified trend or dose-response analysis.
The placebo and AZD9977 150 mg monotherapy records are descriptive only following early arm removal. Their values were 230.3 for placebo and -45.01 for monotherapy, based on 3 and 5 participants analyzed, respectively; no confidence intervals were reported for these estimates. They are not part of the formal four-arm MMRM result and should not be set beside the retained-arm estimates as if they were randomized, fully powered comparisons.
Overall, the posted results describe decreases in mean UACR in each retained arm, with uncertainty around every estimate. They do not establish a clinical benefit or show that adding AZD9977 produces a particular outcome for an individual participant. The evidence should be interpreted as a short-term biomarker analysis in a Phase 2b trial, in light of the revised arm set and the uncertainty in the estimates.
9. Statistical Methods Explained
The primary outcome is continuous: each participant has a measured UACR value, and the reported summary is mean percent change from baseline. For a continuous outcome, the mean describes the average change in a group. It does not imply that every participant changed by that amount, and it can be influenced by the distribution of participant-level values. The posted results give the mean and 95% confidence interval, not a separate standard deviation or standard error.
What does the confidence interval describe?
As general statistical context, a confidence interval expresses the uncertainty in an estimate under the analysis model and its assumptions. A narrower interval indicates greater precision than a wider interval on the same scale. The reported intervals allow readers to assess the precision of each mean change estimate. They are not direct intervals for differences between arms, and they do not identify the range of responses among participants.
For the retained arms, the mean estimates and confidence intervals are -56.39 (-71.53 to -33.21), -42.09 (-64.17 to -6.376), -58.05 (-73.56 to -33.43), and -34.32 (-58.2 to 3.22), respectively. Because the intervals differ in width and overlap, the point estimates alone do not establish a dose ranking. An arm-to-arm inference requires the model's contrast and its uncertainty, not just a visual or numerical comparison of separate means.
Why use a repeated-measures model?
The registry states that the primary endpoint was analyzed with a mixed-effects model for repeated measures, or MMRM. As general explanation, repeated-measures models can use measurements collected at multiple time points while accounting for the fact that measurements from the same participant are related. A mixed-effects framework can estimate group patterns over time and compare groups while incorporating the repeated structure. The exact covariance structure, fixed effects, adjustment variables, and handling of departures from model assumptions are not reported in the registry record.
The registry describes the Week 12 change as calculated from the average of UACR values at Week 12, then analyzed by MMRM. It also says that removal of the AZD9977 150 mg monotherapy and placebo arms led to revised objectives, and that the MMRM included the four remaining arms. This change matters: the formal test describes the reduced set of arms, not the original set of all treatment groups.
What does the F-test test?
The posted analysis reports an F-test statistic of 1.07 for the four retained arms. In general, an omnibus F-test evaluates whether the set of group means is consistent with a common value, against the possibility that at least one differs. It does not identify which arm differs, the direction of any difference, or the size of a particular pairwise contrast. Those questions require specific contrasts and corresponding uncertainty estimates. The registry record does not report such primary pairwise estimates in the listed analysis.
The test is not equivalent to testing whether each combination regimen differs from dapagliflozin alone, nor is it automatically a test of a linear dose trend. The study description mentions assessment of dose response, and a secondary outcome is explicitly named as a dose-response assessment. The details of the dose-response model or its specific result are not reported in the registry record.
Why can over-dispersion matter?
As general statistical context, over-dispersion means that observed variability is greater than a model expects. It is especially relevant for outcomes based on counts or events, where an overly restrictive variance assumption can produce confidence intervals that are too narrow and tests that are too optimistic. The primary outcome is continuous and analyzed using MMRM, so count-data over-dispersion is not the central issue for this endpoint. Distributional behavior, influential observations, and model fit can still affect continuous-outcome inference; the registry record does not report diagnostic results.
How should planning illustrations be read?
Any sample-size planning illustration based on an observed effect is a hypothetical design calculation, not a measure of the trial's achieved power. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such illustrations answer how a future study might be planned under those assumptions. They do not show that the present study had a particular power, and they do not replace the sponsor's analysis.
These general methods explanations do not fill in omitted protocol details. The registry record does not report the model's full specification, a missing-data sensitivity analysis, or a formal multiplicity strategy. Consequently, interpretation should remain tied to the reported estimand, the retained arms, the confidence intervals, and the limits of the information registered.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| F-Test | F test statistics 1.07 | not reported | 0.364 |
The registry's primary analysis is the sponsor-reported MMRM, which includes AZD9977 15 mg, 50 mg, and 150 mg combined with dapagliflozin and dapagliflozin alone. Its reported omnibus result is an F-test statistic of 1.07. The registry also provides group-level mean changes and confidence intervals. These model-based results are the relevant sponsor analysis for interpreting the stated primary endpoint.
A simple recalculation from posted summary statistics, if presented alongside the registry result, would be unadjusted and would not necessarily reproduce the MMRM estimand. It would not account for repeated measurements or any model adjustments, and it could not reconstruct participant-level information from group summaries. It should therefore be treated as a secondary check rather than a replacement for the sponsor's analysis. The registry record does not flag a discrepancy between sponsor results and recalculations.
The two arms removed early are not included in the formal MMRM comparison. Their descriptive estimates do not provide a like-for-like adjusted contrast with the retained groups. The registry explains that the study objectives were revised after those removals and that only descriptive statistics are shown for the removed arms. The formal sponsor analysis therefore takes priority for the primary question as revised; it should not be extended to arms it did not analyze.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary UACR endpoint and six secondary outcomes, including a UACR dose-response assessment, adverse events, serum potassium, and estimated glomerular filtration rate. It also reports four analyses. A trial with several outcomes, time points, doses, and possible comparisons can generate multiple opportunities to find a nominally unusual result. As general statistical context, multiplicity procedures are used to control or describe the increased chance of false-positive findings across a family of tests.
A formal multiplicity adjustment strategy for the primary and secondary outcomes is not reported in the registry record. Nor does the record state how a family of individual dose-versus-comparator tests would be defined or adjusted. The reported F-test is an overall test across the four retained arms; it does not, by itself, resolve multiplicity across the broader outcome set or establish results for every secondary endpoint.
The registry describes a full analysis set including randomized participants whether or not they received study intervention, and says the outcome-specific analyzed count covers participants evaluated for that endpoint. The exact handling of missing Week 12 measurements, any imputation method, and sensitivity analyses for missing data are not reported in the registry record. MMRM can use available repeated measurements under model assumptions, but that general property does not demonstrate that missingness was harmless or that the assumptions held in this trial.
Early removal of the placebo and AZD9977 150 mg monotherapy arms changed the formal analysis population of arms and prompted revision of the study objectives. The registry provides descriptive results for those arms without formal comparison. It does not report the decision process, timing details, or any interim-analysis plan associated with the removals. These omissions limit assessment of how the revised analysis relates to the original statistical plan.
As general interpretation guidance, confidence intervals and tests should be considered with the analysis population, missing-data approach, outcome hierarchy, and multiplicity plan. Where these details are not registered, the uncertainty is not resolved by the point estimates alone.
12. 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 |
|---|---|---|---|
| AZD9977 15 mg + Dapagliflozin 10 mg | 1 | 33 | 3.0% |
| AZD9977 50 mg + Dapagliflozin 10 mg | 3 | 31 | 9.7% |
| AZD9977 150 mg + Dapagliflozin 10 mg | 2 | 34 | 5.9% |
| AZD9977 150 mg | 0 | 6 | 0.0% |
| Dapagliflozin 10 mg | 4 | 33 | 12.1% |
| Placebo | 2 | 5 | 40.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| AZD9977 15 mg + Dapagliflozin 10 mg | 0 of 33 |
| AZD9977 50 mg + Dapagliflozin 10 mg | 2 of 31 |
| AZD9977 150 mg + Dapagliflozin 10 mg | 0 of 34 |
| AZD9977 150 mg | 0 of 6 |
| Dapagliflozin 10 mg | 1 of 33 |
| Placebo | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| AZD9977 15 mg + Dapagliflozin 10 mg | 1 of 33 |
| AZD9977 50 mg + Dapagliflozin 10 mg | 4 of 31 |
| AZD9977 150 mg + Dapagliflozin 10 mg | 13 of 34 |
| AZD9977 150 mg | 5 of 6 |
| Dapagliflozin 10 mg | 7 of 33 |
| Placebo | 2 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | AZD9977 15 mg + Dapagliflozin 10 mg | AZD9977 50 mg + Dapagliflozin 10 mg | AZD9977 150 mg + Dapagliflozin 10 mg | AZD9977 150 mg | Dapagliflozin 10 mg | Placebo |
|---|---|---|---|---|---|---|---|
| Cardiac failure | Cardiac disorders | 0 of 33 | 1 of 31 | 1 of 34 | 0 of 6 | 0 of 33 | 1 of 5 |
| COVID-19 | Infections and infestations | 0 of 33 | 1 of 31 | 0 of 34 | 0 of 6 | 0 of 33 | 1 of 5 |
| Transient ischaemic attack | Nervous system disorders | 0 of 33 | 0 of 31 | 1 of 34 | 0 of 6 | 0 of 33 | 0 of 5 |
| Cardiac failure congestive | Cardiac disorders | 0 of 33 | 0 of 31 | 0 of 34 | 0 of 6 | 1 of 33 | 0 of 5 |
| Left ventricular failure | Cardiac disorders | 0 of 33 | 1 of 31 | 0 of 34 | 0 of 6 | 0 of 33 | 0 of 5 |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | 0 of 33 | 0 of 31 | 0 of 34 | 0 of 6 | 1 of 33 | 0 of 5 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 0 of 33 | 1 of 31 | 0 of 34 | 0 of 6 | 0 of 33 | 0 of 5 |
| Peripheral swelling | General disorders | 0 of 33 | 0 of 31 | 0 of 34 | 0 of 6 | 1 of 33 | 0 of 5 |
| Sudden cardiac death | General disorders | 0 of 33 | 0 of 31 | 0 of 34 | 0 of 6 | 1 of 33 | 0 of 5 |
| Hepatic enzyme increased | Investigations | 1 of 33 | 0 of 31 | 0 of 34 | 0 of 6 | 0 of 33 | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AZD9977 15 mg + Dapagliflozin 10 mg | AZD9977 50 mg + Dapagliflozin 10 mg | AZD9977 150 mg + Dapagliflozin 10 mg | AZD9977 150 mg | Dapagliflozin 10 mg | Placebo |
|---|---|---|---|---|---|---|---|
| Hyperkalaemia | Metabolism and nutrition disorders | 0 of 33 | 1 of 31 | 2 of 34 | 1 of 6 | 3 of 33 | 0 of 5 |
| Chronic kidney disease | Renal and urinary disorders | 1 of 33 | 1 of 31 | 2 of 34 | 1 of 6 | 1 of 33 | 0 of 5 |
| Urinary tract infection | Infections and infestations | 0 of 33 | 1 of 31 | 1 of 34 | 0 of 6 | 3 of 33 | 0 of 5 |
| Nasopharyngitis | Infections and infestations | 0 of 33 | 0 of 31 | 3 of 34 | 0 of 6 | 1 of 33 | 0 of 5 |
| Urinary tract infection bacterial | Infections and infestations | 0 of 33 | 2 of 31 | 1 of 34 | 0 of 6 | 0 of 33 | 0 of 5 |
| Diarrhoea | Gastrointestinal disorders | 0 of 33 | 0 of 31 | 2 of 34 | 0 of 6 | 0 of 33 | 1 of 5 |
| Fall | Injury, poisoning and procedural complications | 0 of 33 | 0 of 31 | 1 of 34 | 0 of 6 | 2 of 33 | 0 of 5 |
| Hypertensive crisis | Vascular disorders | 0 of 33 | 0 of 31 | 2 of 34 | 0 of 6 | 0 of 33 | 0 of 5 |
| Nausea | Gastrointestinal disorders | 0 of 33 | 0 of 31 | 2 of 34 | 0 of 6 | 0 of 33 | 0 of 5 |
| Syncope | Vascular disorders | 0 of 33 | 0 of 31 | 1 of 34 | 0 of 6 | 0 of 33 | 1 of 5 |
Serious events with the highest arm-level rate: covid-19 (20.0%), cardiac failure (20.0%), left ventricular failure (3.2%), osteoarthritis (3.2%), cardiac failure congestive (3.0%).
The registry reports serious adverse events for the treatment groups, with participants at risk and affected counts shown separately. Serious adverse events affected 1 of 33 participants in the AZD9977 15 mg plus dapagliflozin group, 3 of 31 in the 50 mg group, 2 of 34 in the 150 mg group, 0 of 6 in the AZD9977 150 mg monotherapy group, 4 of 33 in the dapagliflozin group, and 2 of 5 in the placebo group. Deaths recorded by arm were 0, 2, 0, 0, 1, and 0, respectively.
These are descriptive counts from groups of differing sizes. They do not establish that a treatment caused an event, and the smaller groups provide limited information about uncommon outcomes. The registry lists COVID-19 and cardiac failure as the leading serious-event terms, each reported as 20.0%; other listed terms include left ventricular failure and osteoarthritis at 3.2%, and cardiac failure congestive and lower gastrointestinal haemorrhage at 3.0%. The registry record does not provide enough detail in this summary to infer comparative risk from these term percentages.
For non-serious adverse events, affected counts were 1 of 33, 4 of 31, 13 of 34, 5 of 6, 7 of 33, and 2 of 5 across the same arm order. Descriptive safety counts should be read alongside the study's short treatment period and limited group sizes. They are not substitutes for a comparative safety analysis.
13. What the Result Does, and Does Not, Mean
The posted primary results show negative mean percent changes in UACR across the four arms retained for the MMRM analysis. The estimates range from -34.32 in the dapagliflozin-alone group to -58.05 in the AZD9977 150 mg combination group, with confidence intervals that reflect substantial uncertainty. The overall F-test statistic is 1.07. These findings describe the measured biomarker over the registered treatment period; they do not establish what happened to every participant or what would happen with longer follow-up.
The statistical result is not a direct estimate of the benefit of adding AZD9977 at each dose. The reported means are within-group changes, while the formal analysis is an omnibus test across arms. Without reported pairwise contrasts and their confidence intervals, the registry record does not quantify the adjusted difference between each combination and dapagliflozin alone. A lack of a clearly separated pattern in the estimates is not proof that the groups are equivalent.
UACR is a laboratory marker. A change in this measure should not be translated automatically into a change in symptoms, heart failure events, kidney outcomes, survival, or quality of life. Those are distinct outcomes, and the primary endpoint is not a direct measure of them. The registry lists eGFR and safety outcomes among the secondary measures, but their detailed results are not included in the registry record described for the primary outcome.
The results also do not answer the original question across every randomized arm in the same way. The registry says placebo and AZD9977 150 mg monotherapy were removed early, with descriptive statistics only for those arms. Their small analyzed counts and lack of formal comparison make them unsuitable for drawing strong comparative conclusions against the retained groups.
As general statistical context, a non-significant or imprecise comparison cannot establish equivalence, and a point estimate cannot establish a causal effect without the design and analysis supporting that inference. The posted estimates and test should be understood as evidence from a randomized, short-term Phase 2b biomarker study, with the limitations of the revised analysis and the unreported statistical details kept in view. No medical advice follows from these registry results.
14. Why This Trial Matters Statistically
This trial raises several useful statistical issues for clinical researchers. First, its primary outcome is continuous and reported as percent change, making both the scale and the direction of change important. Negative values denote decreases from baseline, but a group mean does not reveal the distribution of individual responses. Confidence intervals help express estimation uncertainty, while remaining distinct from participant-level ranges.
Second, the registry reports an omnibus F-test across the four arms retained for formal analysis. That test addresses an overall group question, not a collection of dose-specific comparisons. Reading it as if it answered whether every AZD9977 dose differs from dapagliflozin alone would overstate what the test establishes. The reported group means are informative descriptively, but direct contrasts are needed for dose-versus-comparator estimates.
Third, early arm removal changes the scope of inference. The primary MMRM includes the combination groups and dapagliflozin alone, while placebo and AZD9977 monotherapy are presented descriptively. Researchers need to keep the revised analysis distinct from the original set of arms and avoid treating all displayed values as equally supported comparisons.
Finally, the registry record leaves important design and analysis details unreported, including the full MMRM specification, missing-data sensitivity analyses, and multiplicity strategy. This makes transparent reporting especially important: readers need to know which participants and arms contribute to each result, what contrast is tested, and how uncertainty and missingness are handled. The trial is a practical example of why a reported mean, an overall test, and a clinical interpretation are related but not interchangeable.
15. 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 endpoint is a short-term laboratory outcome measured through Week 12. The registry record does not establish how well that change predicts longer-term kidney or heart failure outcomes. Results for this biomarker should therefore remain distinct from claims about clinical events, symptoms, or sustained effects.
The formal analysis was revised after early removal of AZD9977 150 mg monotherapy and placebo. The registry says descriptive statistics, without formal comparison, are reported for those arms. The reasons and timing details for the removals and the original analysis plan are not reported in the registry record. The descriptive results for the removed arms should not be interpreted as equivalent to the retained-arm MMRM result.
The analyzed counts vary by arm: 32, 23, 25, and 28 in the retained groups, and 5 and 3 in the removed groups. Confidence intervals are not reported for the monotherapy and placebo estimates. The limited information for those arms constrains interpretation, especially for comparisons and dose-response conclusions.
The registry does not report the full MMRM specification, model diagnostics, detailed missing-data methods, sensitivity analyses, or a multiplicity plan. It also does not report formal pairwise contrasts for the primary endpoint in the listed analysis. These omissions make it difficult to assess the robustness of the estimates or determine the precision of specific treatment differences from the registry record alone.
Finally, the primary endpoint summarizes UACR change and cannot by itself capture the full balance of benefits and harms. Safety counts are descriptive, and sparse event counts should not be treated as precise comparative risk estimates. These limitations are specific to the posted trial record and do not negate the value of the reported estimates; they define the boundaries of what can be concluded from them.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease — NCT04595370.
- Registry record last updated 2024-11-19; status last verified 2024-10.
- Results first posted 2024-11-19.
- 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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19. Record Summary
NCT04595370 is a completed randomized, parallel-group Phase 2b study of AZD9977 and dapagliflozin in participants with heart failure and chronic kidney disease. The registry reports enrollment of 153 and identifies AstraZeneca as sponsor. The primary outcome was percent change from baseline in UACR at Week 12.
The formal primary analysis included AZD9977 15 mg, 50 mg, and 150 mg combined with dapagliflozin 10 mg, alongside dapagliflozin 10 mg alone. The registry reports mean changes, 95% confidence intervals, and an omnibus F-test statistic of 1.07. Placebo and AZD9977 150 mg monotherapy were removed early and have descriptive results only.
The posted findings describe short-term changes in a laboratory marker, not direct evidence about symptoms or longer-term clinical outcomes. Important details, including the full model specification, missing-data sensitivity analyses, and multiplicity strategy, are not reported in the registry record.