Next Generation ORS: Comparing ORS With Calcium vs Standard ORS in Reducing Severity of Acute Watery Diarrhea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Next Generation ORS: Comparing ORS With Calcium vs Standard ORS in Reducing Severity of Acute Watery Diarrhea (NCT05814042), a randomized phase 2, phase 3 study. The primary outcome is Stool Output.

2. Clinical Question

3. Trial Design

This is a randomized, parallel-group trial with quadruple masking, listed as spanning Phase 2 and Phase 3. The registry reports enrollment of 396 and a completed status. The study compares next-generation oral rehydration solution with calcium against standard oral rehydration solution. The record gives the trial start as 2023-08-21 and primary completion as 2024-12-31.

The official title identifies adults with acute watery diarrhea. The registry lists diarrhea and cholera as conditions. It does not report the randomization procedure, allocation ratio, masking roles, sites, or further eligibility criteria in the registry record. Quadruple masking describes the reported masking category; the identities of the masked groups are not reported in the registry record.

The intervention descriptions are not fully consistent: the experimental arm is named as next-generation ORS, while the arm description calls it a nutrient-based intervention and a nutrition supplement. The comparator is described as current standard control ORS and as standard-of-care ORS. These labels support identifying the intended comparison, but they do not establish the exact ingredients, dose, or administration schedule.

The primary outcome is stool output, with daily measures on Day 1, day 2, and Day 3, as well as a measure over the entire 3 days. The record says total output covers the cumulative stool weight over the 72-hour study period or until diarrhea resolved, whichever occurred first. It notes that the number analyzed in individual rows differs from the overall sample size because diarrhea resolved over time. Further details of analysis populations and handling of these changing numbers are not reported 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: Work Flow: Triage =\>ER/SSU: Step 1: Verbal Consent, Study Nurse (SN)/ Field Research Supervisor (FRS) put a tag on bed and write screening ID on top of Study CRF=\>Study Ward/Allocated Space: Step 2: HW Screening Form; Step 3: FRS if enrollment criteria met consent done; Step 4: SN Complete admission section of CRF including clinical signs of dehydration; Step 5: Randomization to 72h or till diarrhea cease=\> Discharge Step-6: SN/PRP record outcome; Step 7: FRS Follow up at enrollment day 7.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The number analyzed in individual rows differs from the overall sample size because diarrhea resolved over time.

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 Stool Output, measured over Day 1, day 2, Day 3, and entire 3 days.

Stool output is the primary endpoint. The record defines daily stool output as the total weight, in grams, of all stools passed during a given 24-hour intervention day. Total stool output is the cumulative weight of stools passed over the entire 72-hour study period or until diarrhea resolved, whichever occurred first. The endpoint therefore expresses stool production as a continuous measurement of weight rather than as a count of bowel movements.

Stool output can be used to quantify the amount of diarrhea during the observation period. As a general statistical point, a continuous endpoint preserves information about the magnitude of measured output rather than reducing it to categories such as improved or not improved. Its interpretation depends on how measurements are collected, how the observation window is defined, and how participants whose diarrhea resolves earlier are handled.

The registry names daily and cumulative time points, but the numerical results, group summaries, effect estimates, and confidence intervals are not reported in the registry record. The number analyzed can differ across individual rows because diarrhea resolved over time. Thus the planned endpoint definitions are available, but the registry entries do not establish the observed size or precision of a treatment-group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group trial with quadruple masking. In a parallel design, participants are assigned to one group and outcomes are compared between groups. As a general statistical principle, randomization can reduce the risk that treatment assignment is systematically related to participant characteristics. The trial record does not report the randomization method, allocation ratio, or masking roles, so those implementation details cannot be assessed from the registry record.

What does a mean represent?

The primary outcome is identified as a mean of a continuous measure, with standard deviation as the stated measure of dispersion. Stool output is recorded in grams. A mean describes the average measured output in a group, while a standard deviation describes how spread out individual measurements are around that group average. These are descriptive summaries. The registry record does not report the means or standard deviations for the primary endpoint, so the group summaries cannot be interpreted numerically.

General statistical explanation: an estimated difference between group means would describe the contrast in average stool output, while a confidence interval would express the uncertainty around that estimate under the analysis assumptions. A narrow interval would indicate greater precision than a wide one. Neither an estimate nor a confidence interval for the primary outcome is reported in the registry record. No p-value for the primary comparison is reported either. Without these results, statistical significance and the range of plausible effect sizes cannot be evaluated.

Why do the time points matter?

The endpoint is assessed daily on Day 1, day 2, and Day 3, and cumulatively over the entire 3 days. Daily and cumulative measurements answer different descriptive questions. A daily value concerns stool output in a specified 24-hour intervention day. The cumulative value covers the 72-hour period or ends when diarrhea resolves, whichever occurs first. General statistical explanation: repeated measurements on the same participant are related, so an analysis that uses multiple time points may need to account for that relationship. The statistical model and its assumptions are not reported in the registry record.

The registry explicitly notes that the number analyzed in individual rows differs from the overall sample size because diarrhea resolved over time. This can arise naturally when the outcome window ends at resolution, but the record does not say exactly how measurements after resolution are represented in each analysis. It also does not report whether participants with incomplete measurements were excluded, included under a particular rule, or handled by another method. Therefore the impact of changing analysis counts on estimates and their precision is not known from this record.

What can be said about planning calculations?

The registry states general assumptions for a planning illustration based on the observed effect: a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not a report of the trial's original design justification. Numerical planning estimates are not included in the registry record for this account. Such sample-size illustrations are not observed power and do not establish whether the trial was adequately powered for its actual results.

The registry does not report the sample-size justification used to design the trial, the target effect considered during planning, or whether any interim analyses were conducted. It also does not report the statistical plan in sufficient detail to identify the primary contrast, covariate adjustment, model, or method for calculating uncertainty. Those missing details prevent a full reconstruction of the analysis.

How should multiple analyses be understood?

The record lists 36 analyses and several outcomes and time points. General statistical explanation: when many comparisons are examined, the chance of at least one apparently unusual result can increase if each is assessed without accounting for multiplicity. Adjustment methods can address this issue, but the record does not state whether any method was used or which comparison was designated for confirmatory interpretation. It would therefore be inappropriate to infer a multiplicity strategy from the count of analyses alone.

Overall, the design and endpoint definitions establish what was intended to be compared, while the absent numerical results and analysis details limit assessment of the findings. The record does not report enough information to evaluate model fit, distributional assumptions, sensitivity analyses, or the robustness of the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures and 36 analyses. The primary endpoint includes daily stool output on Day 1, day 2, and Day 3, together with cumulative output over the entire 3 days. Several secondary outcomes are also listed: duration of diarrhea, stool frequency, vomiting, the percentage of patients requiring unscheduled intravenous therapy, and ORS intake. These multiple outcomes and time points create several possible comparisons, but their presence alone does not reveal which analyses were designated as primary or how results were to be interpreted jointly.

The registry record does not report a multiplicity adjustment, a hierarchy of endpoints, or a prespecified rule for choosing among time points. General statistical explanation: testing multiple hypotheses without adjustment can increase the chance of finding at least one result that appears statistically notable by chance. A prespecified testing strategy can help control that risk. No such strategy is reported in the registry record, so no claim about control of multiplicity is warranted.

Missing-data handling is also not reported. The record notes that the number analyzed in individual rows differs from the overall sample size because diarrhea resolved over time. That statement identifies a reason for changing analysis counts, but does not explain whether other observations were missing, how resolution affected later measurements, or what analysis population was used at each time point.

The registry record does not state whether analyses followed intention-to-treat principles, whether participants were excluded after randomization, or whether sensitivity analyses were conducted. It also does not describe imputation or other methods for incomplete data. These omissions limit evaluation of whether the reported comparisons, if available, would reflect all randomized participants and how sensitive they might be to assumptions about missing observations. The numerical results needed to examine these issues are not reported in the registry record.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypovolemic shock (0.6%).

The registry lists serious and other adverse-event counts separately for four entries: ORS With Calcium: Aim 1, ORS: Aim 1, ORS With Calcium: Aim 2, and ORS: Aim 2. For Aim 1, each group entry reports 30 at risk, zero serious adverse events, zero other adverse events, and zero deaths. For Aim 2, the ORS With Calcium entry reports 167 at risk, 1 serious adverse event, 14 other adverse events, and zero deaths; the ORS entry reports 169 at risk, 1 serious adverse event, 11 other adverse events, and zero deaths.

Hypovolemic shock is listed among the serious adverse-event terms at 0.6%. The registry record does not provide further event-level context in the registry record for this account. These counts describe reported events in the listed entries; they do not by themselves establish whether an event was caused by an intervention. The record does not report attribution, event timing, severity criteria, or a statistical comparison of adverse-event rates. The Aim 1 and Aim 2 entries should be read as separately labeled registry groups, not silently combined. No deaths are reported in any of the four entries.

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

The record establishes that a randomized comparison was conducted between next-generation ORS with calcium and standard ORS, with stool output designated as the primary endpoint. It defines daily and cumulative stool-output measures and lists several secondary outcomes. These details describe the question and outcome framework, but they do not establish what the trial found.

Numerical results for the primary endpoint are not reported in the registry record. Without the group summaries or a between-group estimate, there is no basis in the registry record to state which group had greater or lesser stool output, or by how much. Without confidence intervals, the precision of a possible difference cannot be assessed. Without a reported p-value or other inferential result, statistical evidence for a difference cannot be characterized either. The absence of these results should not be interpreted as evidence that the groups were equivalent, or as evidence that they differed.

The registry reports adverse-event counts, but these counts are not a substitute for efficacy results. Nor do the event listings alone establish causal attribution or comparative safety. The record does not provide the methodological detail needed to assess differences in exposure, follow-up, or adverse-event ascertainment.

General statistical explanation: an observed estimate describes the result in the analyzed data, while its uncertainty indicates how much the estimate might vary under the model and sampling process. A clinically meaningful interpretation also depends on the context of the outcome and the prespecified question. In this case, the registry entries do not include an estimated effect or its uncertainty, and no threshold for a clinically important difference is reported.

Thus, the registry information supports a description of trial design, endpoint definitions, and listed adverse events, but not a conclusion about whether the calcium-containing solution changed stool output. The completed status and enrollment entry do not fill that result gap. Interpretation should remain limited to what is actually reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises a useful statistical question about measuring an acute, changing clinical outcome. Stool output is recorded as a continuous quantity across daily periods and as a cumulative measure. That approach can preserve information about the amount of output, but the interpretation depends on the observation window and how measurements are handled when diarrhea resolves before the end of follow-up.

The registry explicitly notes that the number analyzed in individual rows differs from the overall sample size because diarrhea resolved over time. This makes the analysis population at each time point important. A reader needs to know whether different row counts reflect outcome-related end of observation, missing measurements, exclusions, or a combination. The record explains that resolution affects counts but does not provide the analysis details needed to separate those possibilities.

The trial also lists multiple outcome measures, several stool-output time points, and 36 analyses. As a general statistical issue, a broad set of comparisons requires a clear plan for identifying confirmatory results and interpreting multiplicity. The registry information does not report such a plan. This makes it especially important not to select a result from a collection of analyses without knowing how it was prespecified or adjusted.

Randomization and quadruple masking are important design features reported in the record, but neither replaces transparent reporting of estimates, uncertainty, and analysis methods. The outcome results are not reported in the registry record, and the model and missing-data approach are not specified in the registry record for this account. The example therefore illustrates how design information can be available while the numerical information needed to evaluate a primary comparison remains absent.

For clinical researchers and statisticians, the key lesson is that endpoint definitions, analysis counts, and design labels are only part of an interpretable trial record. Results need to be paired with their denominators, statistical estimates, uncertainty, and clear account of how changing observations were handled. Without those elements, the question can be described, but its empirical answer cannot be assessed from the registry record.

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 principal limitation for interpretation is that numerical primary-outcome results are not reported in the registry record. The endpoint definition is available, but the group means, standard deviations, effect estimate, confidence interval, and p-value are not. Therefore the direction, magnitude, and precision of the primary comparison cannot be assessed.

Analysis counts differ across individual rows because diarrhea resolved over time. The record does not specify how the resulting changes in observation time were treated in each analysis, how missing measurements were handled, or which analysis population was used. The statistical model, covariate adjustment, and sensitivity analyses are also not reported in the registry record for this account.

There are multiple outcome measures, stool-output time points, and 36 analyses, but the registry record does not describe a multiplicity plan or identify a hierarchy among comparisons. Without that information, the intended confirmatory analysis cannot be distinguished from other analyses.

Intervention descriptions are inconsistent in wording: the experimental treatment is named as next-generation ORS with calcium, while its arm description refers to a nutrient-based intervention and a nutrition supplement. The record does not give the formulation, dose, or administration schedule. The standard comparator is identified as ORS, but its details are not reported either.

The record names quadruple masking but does not identify the masked roles or describe how masking was maintained. It also does not report detailed eligibility criteria, trial sites, the randomization method, or the original sample-size justification. These omissions do not establish that the study lacked such procedures; they mean that these details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Next Generation ORS: Comparing ORS With Calcium vs Standard ORS in Reducing Severity of Acute Watery Diarrhea — NCT05814042.
• Registry record last updated 2026-04-14; status last verified 2025-07.
• Results first posted 2026-04-14.
• 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.

18. Record Summary

The registry describes a completed randomized, parallel-group, quadruple-masked trial spanning Phase 2 and Phase 3. It lists enrollment of 396 and compares next-generation oral rehydration solution with calcium against standard oral rehydration solution in adults with acute watery diarrhea. The reported start date is 2023-08-21, and primary completion is listed as 2024-12-31.

Stool output is the primary endpoint, defined by daily stool weight and cumulative stool weight over the entire 3 days or until diarrhea resolved. The registry notes that the number analyzed varies across rows because diarrhea resolved over time. Secondary outcomes include duration of diarrhea, stool frequency, vomiting, unscheduled intravenous therapy, and ORS intake.

Numerical primary-outcome results and detailed analysis methods are not reported in the registry record. Adverse-event counts are listed for Aim 1 and Aim 2 entries, with zero deaths in all entries. The available information describes the design and outcome framework but does not establish the direction, size, or precision of the primary comparison.