Investigations of the Optimum Serum Bicarbonate Level in Renal Disease.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigations of the Optimum Serum Bicarbonate Level in Renal Disease. (NCT01574157), a randomized na study. The primary outcome is Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1).

2. Clinical Question

The registry describes the study purpose as assessing whether sodium bicarbonate would lower urine protein levels that indicate kidney damage in people with diabetes and chronic kidney disease. The posted primary endpoint narrows that broad purpose to urinary TGF-b1. Other listed outcomes include urinary markers and estimated glomerular filtration, but they are not the primary question.

3. Trial Design

This was a randomized, double-masked, parallel-group trial with 74 participants enrolled. The registry lists sodium bicarbonate and placebo as the two interventions. The arm descriptions specify daily treatment over six months: sodium bicarbonate was prescribed at 0.5 meq per 1 kilogram of lean body weight, while the placebo group took an identical number of placebo tablets. The exact method used to generate the random allocation sequence and maintain masking is not reported in the registry record.

The posted primary outcome data include 35 participants in the sodium bicarbonate arm and 39 in the placebo arm. These are the arm counts associated with the outcome summary; the registry does not explain in this record whether these counts represent everyone randomized, everyone with an outcome measurement, or another analysis population. Further details about exclusions, adherence, and participant flow are not reported in the registry record.

The trial is listed as completed. Its recorded start date is 2012-11-05, and its primary completion date is 2018-05-01. The phase is listed as NA. The sponsor is the VA Office of Research and Development.

The study lists six outcome measures and six analyses. The primary endpoint is change in urinary TGF-b1. Five secondary outcomes are change in urinary KIM-1, NGAL, fibronectin, urinary albumin, and estimated glomerular filtration (eGFR). The registry does not describe the full analysis plan, the exact timing of every secondary outcome, or how the multiple outcomes were handled statistically.

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:

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 in Urinary Transforming Growth Factor Beta 1 (TGF-b1), measured over The mean of the 3-month and 6-month urinary TGF-b1 measurement will be compared to the baseline value between the groups..

The primary endpoint is change in urinary transforming growth factor beta 1 (TGF-b1), reported as percent change. TGF-b1 is described in the registry as a marker of renal fibrosis. The endpoint description says the mean of the urinary measurements at 3 months and 6 months would be compared with the baseline value between the treatment groups. The arm summaries are identified as geometric means with 95% confidence intervals.

A urinary marker is a measured biological outcome rather than a direct report of how a participant feels or functions. The endpoint is used to assess whether the groups differ in a marker relevant to the study’s stated kidney-damage question. A change in such a marker, by itself, does not establish a change in kidney function or other clinical outcomes. The registry record does not give a detailed biological rationale for selecting TGF-b1 over the other urinary measures, nor does it report a threshold defining a clinically important change.

The registry also lists five secondary outcomes: urinary KIM-1, NGAL, fibronectin, urinary albumin, and eGFR. Their presence indicates that the study assessed more than one measure, but the primary endpoint remains the prespecified focus named in the record. Details such as the specific laboratory procedures and handling of repeated measurements are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the arm summaries as geometric means and their uncertainty as 95% confidence intervals. It also reports a between-group analysis labeled as a mean difference in final values. It does not name a statistical test or model, so no specific method should be inferred from the reported label alone.

What a confidence interval conveys

In general, a confidence interval expresses the uncertainty associated with an estimate under the assumptions of the analysis used to construct it. A narrower interval indicates greater precision on the scale being analyzed, while a wider interval indicates less precision. A 95% confidence interval is not a guarantee that a particular interval contains the true value, and it does not describe the range of individual participants’ responses.

For the reported group comparison, the 95% confidence interval runs from -9.6 to 40.1 around the estimate of 12.6. Because the interval includes zero, the posted data do not pin down the direction of the difference. This is a statement about the uncertainty of the estimate, not proof that the groups are identical. Conversely, the positive point estimate alone is not enough to establish that the treatment group differs from placebo. No p-value is reported.

Arm summaries and between-group estimates

The geometric mean summaries are presented separately for each arm. A between-group contrast answers a different question: how far apart the groups are according to the analysis used. The arm-level confidence intervals should not be treated as though they were the confidence interval for the contrast. The reported comparison is the direct summary for the between-group question, although the registry does not give enough detail to reconcile its “final values” label with the endpoint description based on change from baseline.

In general, geometric means are used for quantities whose distributions are suitably handled on a logarithmic scale, often when values are skewed. This can make a central summary more appropriate than an arithmetic mean for some positive measurements. The record does not describe the distribution of TGF-b1, any transformation, or the rationale for choosing this summary. The endpoint is described as percent change, so the exact implementation and scale of the analysis are not clear from the registry record.

What the design contributes

Randomization is intended to create groups that are comparable, on average, at the start of a trial. Double masking is intended to limit effects of treatment knowledge on participant experience, care, or assessment. These design features can strengthen interpretation of a between-group comparison, but they do not remove uncertainty or replace details about allocation, adherence, missing observations, and analysis methods. Those implementation details are not reported in the registry record.

The trial used a parallel-group design: participants were assigned to one of the groups rather than described as receiving both treatments in sequence. The posted arm counts for the primary outcome are 35 and 39. The record does not state whether the analysis followed an intention-to-treat principle, how participants without measurements were handled, or whether any covariates were included.

Planning calculations and observed estimates

Any sample-size figures associated with the results should be understood as planning illustrations based on the observed effect, not as the trial’s original design justification. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such calculations explore how a hypothetical future study might be planned under those assumptions. They are not evidence about the probability that this completed trial detected an effect, and they are not observed power.

The registry record does not report the trial’s own sample-size justification, its assumed effect, or the statistical plan used to determine enrollment. The planning assumptions therefore should not be attributed to the original protocol. The record also does not report whether interim analyses were planned or conducted.

Multiple outcomes and incomplete methods

The record lists six outcome measures and six analyses, including the primary endpoint and five secondary outcomes. When several outcomes are examined, the chance of at least one apparently unusual result can increase if the analyses are interpreted without accounting for multiplicity. In general, multiplicity procedures can control or describe this issue, but the registry record does not report whether any such procedure was used. The six listed analyses should not be assumed to represent every analysis conducted.

Important details remain unavailable in the record, including the statistical model, handling of missing data, analysis population, covariate adjustment, and any sensitivity analyses. These omissions limit the ability to reproduce the analysis or assess how robust the estimate is to alternative reasonable methods. The reported estimate and interval can still be described, but conclusions about unreported methods are not warranted.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s comparison as a mean difference in final values of 12.6, with a 95% confidence interval from -9.6 to 40.1. No p-value is reported. The confidence interval includes zero, and the record does not provide enough methodological detail to reconstruct the sponsor’s analysis exactly.

The primary endpoint description refers to the mean of the 3-month and 6-month urinary TGF-b1 measurements compared with baseline between groups. The reported analysis label, “Mean Difference (Final Values),” does not fully explain how that analysis corresponds to the endpoint description. The registry record does not specify the model, scale, or adjustments used. The sponsor’s reported estimate should therefore be read as the posted analysis, without assuming it is a change-score contrast or a particular adjusted estimate.

No discrepancy between the posted summary and sponsor analysis is flagged in the record, and no separate recalculated comparison is reported among the registry entries available for this interpretation. The sponsor’s analysis remains the direct reported between-group result. Its uncertainty should be conveyed through the confidence interval rather than replaced by an unsupported reconstruction.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and six analyses: the primary urinary TGF-b1 endpoint and five secondary outcomes. Examining multiple outcomes raises a general statistical concern: without an appropriate plan, the chance of finding at least one result that appears notable by chance can increase. This does not mean that any particular result is false; it means that the set of analyses needs to be interpreted in light of how many questions were examined and how they were prioritized.

The record does not report whether the trial used a multiplicity adjustment, a hierarchical testing procedure, or another strategy for interpreting the secondary outcomes. It also does not give a complete analysis plan that would show which outcomes were confirmatory and which were exploratory. The primary outcome is identified, but that designation alone does not establish how the other outcomes were handled.

Details about missing data and analysis populations are also not reported in the registry record. The arm counts associated with the primary outcome are 35 for sodium bicarbonate and 39 for placebo, but the record does not say whether these are all randomized participants or only those with usable outcome data. It does not describe missing measurements, reasons for missingness, imputation, exclusions, or whether participants were analyzed according to their randomized assignment.

These gaps affect how fully the results can be assessed. Missingness can matter when the availability of outcome measurements is related to treatment assignment or participant characteristics. In general, different assumptions about missing observations can affect estimates, but the record does not provide the information needed to assess that possibility. The registry also does not report sensitivity analyses that might show whether conclusions change under alternative assumptions.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The posted safety figures list zero serious adverse events in the sodium bicarbonate group among 35 participants at risk and zero in the placebo group among 39 participants at risk. The figures also list zero other adverse events in each group and zero deaths in each group. No serious adverse event terms are listed.

These are counts recorded in the registry, not proof that no adverse events occurred outside the categories or reporting framework represented in the posted results. The record does not describe how adverse events were defined, collected, graded, or attributed to treatment. It also does not provide event-level narratives or follow-up details. With zero events recorded in these categories, the data do not support estimating a comparative event effect from a nonzero event count; they should be read as the registry’s reported counts rather than as a comprehensive safety assessment.

The at-risk counts are the arm counts shown for safety. The registry does not explain whether those counts reflect all randomized participants or a particular safety population. These figures describe reported events during the recorded study period and do not establish safety beyond the trial’s specified follow-up.

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

The main statistical result is a reported between-group mean difference in final values of 12.6, with a 95% confidence interval from -9.6 to 40.1. The interval includes zero and spans values in both directions. The estimate is therefore uncertain about the direction and size of the group difference. No p-value is reported, and the record does not provide a clinically important threshold for interpreting the scale.

The arm summaries show a geometric mean percent change of 7.6 for sodium bicarbonate and -4.4 for placebo, each with its own 95% confidence interval. Those summaries are not interchangeable with the reported between-group contrast. The comparison’s label and the endpoint description are not fully aligned in the registry record, which limits interpretation of exactly what scale the difference represents.

The outcome is urinary TGF-b1, described as a marker of renal fibrosis. A marker can provide evidence about a biological process, but a result on a marker does not, by itself, establish what happened to kidney function, symptoms, or other clinical outcomes. The registry lists eGFR and several other secondary outcomes, but the registry entries available for this interpretation do not include their results.

The record supports a careful description of the posted estimate and its uncertainty. It does not support a definitive conclusion about the size of a treatment-group difference, nor does it establish that the groups were equivalent. The sample-size illustrations, if consulted, are planning exercises based on the observed effect and stated assumptions; they are not observed power or a substitute for the confidence interval.

In general, a randomized, double-masked comparison is designed to reduce some sources of bias. However, the available registry information does not describe allocation procedures, missing data, adherence, the statistical model, or analysis populations. These omissions leave important questions about implementation and analysis unresolved. The posted result should be interpreted within those limits.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a randomized, double-masked comparison with a biomarker endpoint and a reported confidence interval that leaves substantial uncertainty about the between-group estimate. It illustrates why the point estimate, arm-level summaries, and comparison interval answer distinct questions and should not be treated as interchangeable.

The registry identifies a primary endpoint while also listing five secondary outcomes. That structure makes the distinction between a primary question and a broader set of measurements important. Without a reported multiplicity strategy or complete analysis plan, readers cannot tell how the full set of outcomes was interpreted statistically. This is a general issue for trials that measure several outcomes, not a claim that any particular result is invalid.

The record also illustrates the value of clear alignment between an endpoint definition and the reported analysis. The primary description refers to change from baseline using measurements at 3 months and 6 months, whereas the reported comparison is labeled as a mean difference in final values. The missing detail does not erase the posted estimate, but it limits the ability to understand precisely how it was derived.

Finally, the confidence interval communicates uncertainty more directly than a binary reading of whether an effect is present. Here the interval includes zero and allows values in either direction. Statistical interpretation therefore depends on the estimate, its precision, the endpoint’s meaning, and the limits of the record—not simply on whether a single threshold is crossed.

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.

Several trial-specific limitations of interpretation arise from the registry record. First, the reported primary analysis is labeled as a mean difference in final values, while the endpoint description specifies comparing the mean of 3-month and 6-month measurements with baseline. The record does not explain how these descriptions relate, or identify the precise model and scale used for the reported estimate.

Second, the statistical methods are incompletely described. The record does not report the allocation procedure, the analysis population, covariate adjustment, handling of missing data, or sensitivity analyses. Although the study is described as randomized and double-masked, details needed to assess implementation are not included in the record.

Third, outcome reporting is limited for interpretation across the study. Five secondary outcomes are listed, but their results are not included in the registry record. The registry does not report whether multiplicity was addressed or how secondary analyses were prioritized. The record also does not give a clinically important threshold for the primary outcome, making it difficult to judge the practical importance of values compatible with the confidence interval.

Finally, the safety figures are limited to the posted counts and do not include definitions, collection methods, event descriptions, or details of the safety population. The outcome counts associated with the primary endpoint are 35 and 39, but the record does not explain whether those counts represent all randomized participants or a subset with available measurements. These limitations do not change the posted numbers; they constrain how broadly and precisely they can be interpreted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Investigations of the Optimum Serum Bicarbonate Level in Renal Disease. — NCT01574157.
• Registry record last updated 2019-08-28; status last verified 2019-08.
• Results first posted 2019-08-28.
• 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.

19. Record Summary

NCT01574157 is a completed randomized, double-masked, parallel-group trial sponsored by the VA Office of Research and Development. It enrolled 74 participants and compared daily sodium bicarbonate with placebo over six months in people with diabetes and chronic kidney disease.

The primary outcome was change in urinary TGF-b1, described as a marker of renal fibrosis. The reported between-group mean difference in final values was 12.6, with a 95% confidence interval from -9.6 to 40.1; no p-value was reported. The interval includes zero. The registry also lists five secondary outcomes, but their results are not included in the available record details. It reports zero serious adverse events, zero other adverse events, and zero deaths in each group.