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 Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial (NCT02552888), a randomized phase 2 study. The primary outcome is Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02552888 |
| Phase | Phase 2 |
| Condition | Chronic Kidney Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 70 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Tulane University |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned patients with chronic kidney disease. The registry record reports enrollment of 70 and lists chronic kidney disease as the condition. It does not report further eligibility details in the record, such as disease stage or other participant characteristics, so the population represented by the results cannot be characterized more narrowly from these registry entries.
Intervention
The treatment arm received immediate release sodium nitrite 40 mg by mouth twice per day and isoquercetin 225 mg by mouth once per day. The trial summary describes the study as testing combination therapy in relation to endothelial function and inflammation. The posted primary endpoint was mean percentage change in endothelium-dependent flow-mediated vasodilation over 12 weeks.
Comparator
The comparison group received identical placebos. The study was randomized, quadruple masked, and parallel in design, according to the registry record. These design labels describe how the trial was organized; the record does not provide further detail about how masking was maintained or which people were masked.
Primary question
The central statistical question is how mean percentage change in flow-mediated vasodilation over 12 weeks was described for the treatment and placebo groups, and how precise those group estimates were. The posted values are 1.1 with a 95% confidence interval from -0.1 to 2.3 for treatment, and 0.3 with a 95% confidence interval from -0.9 to 1.5 for placebos. These are group summaries. A between-group estimate and test are not reported in the registry record, so these values alone do not establish the size or statistical uncertainty of a treatment-versus-placebo contrast.
3. Trial Design
The NICE Trial is listed as a phase 2 randomized study with a parallel model and quadruple masking. Its status is completed. The registry record identifies Tulane University as sponsor and reports enrollment of 70. The recorded study start is 2016-03, and primary completion is 2017-06. These dates describe the record; they do not supply further information about recruitment duration or follow-up beyond the outcome timeframes listed.
The treatment group received immediate release sodium nitrite 40 mg by mouth twice per day together with isoquercetin 225 mg by mouth once per day. The comparator group received identical placebos. The registry record does not describe the allocation sequence, concealment procedures, adherence, or how the masking was implemented. Those details are not reported in the registry record.
The primary outcome was mean percentage change in endothelium-dependent flow-mediated vasodilation over 12 weeks. The listed measurement time points were baseline, 6 weeks, and 12 weeks. Secondary outcomes covered changes in endothelial function biomarkers and inflammatory biomarkers, as well as LDL as an oxidative stress biomarker. The registry record lists 21 outcome measures and 9 posted secondary outcomes. It does not report results for those secondary outcomes in the registry record for this analysis.
Design features such as randomization and masking can reduce some sources of bias, but they do not by themselves resolve questions about missing observations, analysis choices, precision, or outcome reporting. The registry record does not provide details of the randomization process, a protocol-level statistical analysis plan, or an account of participant flow. Those details should not be inferred from the design labels.
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
| Stage | Treatment | Placebos |
|---|---|---|
| STARTED | 35 | 35 |
| COMPLETED | 34 | 34 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Treatment | Placebos |
|---|---|---|
| Lost to Follow-up | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Mean Changes Over 12 Weeks (95% CI)
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 | Treatment | Placebos | Total |
|---|---|---|---|---|
| Participants analysed | 35 | 35 | 70 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 19 | 19 | 38 |
| Age, Categorical: >=65 years | Participants | 16 | 16 | 32 |
| Age, Continuous | years | 61.3 (SD 10.4) | 62.2 (SD 10.2) | 61.8 (SD 10.3) |
| Sex: Female, Male: Female | Participants | 13 | 13 | 26 |
| Sex: Female, Male: Male | Participants | 22 | 22 | 44 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 17 | 15 | 32 |
| Race (NIH/OMB): White | Participants | 16 | 20 | 36 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 35 | 35 | 70 |
| Baseline Metabolic Panel of Study Participants by Treatment Allocation: Fasting plasma glucose, mean, mg/dL | mg/dL | 119 (SD 44) | 124 (SD 70) | 121.5 (SD 57) |
| Baseline Metabolic Panel of Study Participants by Treatment Allocation: Total cholesterol, mean, mg/dL | mg/dL | 178 (SD 43) | 171 (SD 50) | 174.5 (SD 46.5) |
| Baseline Metabolic Panel of Study Participants by Treatment Allocation: HDL-cholesterol, mean, mg/dL | mg/dL | 48 (SD 13) | 47 (SD 14) | 47.5 (SD 13.5) |
| Baseline Metabolic Panel of Study Participants by Treatment Allocation: LDL-cholesterol, mean, mg/dL | mg/dL | 107 (SD 34) | 100 (SD 37) | 103.5 (SD 35.5) |
| Baseline Blood Pressure of Study Participants by Treatment Allocation: Systolic blood pressure, mean, mmHg | mmHg | 129 (SD 15) | 129 (SD 15) | 129 (SD 15) |
| Baseline Blood Pressure of Study Participants by Treatment Allocation: Diastolic blood pressure, mean, mmHg | mmHg | 73 (SD 7) | 75 (SD 11) | 74 (SD 9) |
| Baseline Body Mass Index of Study Participants by Treatment Allocation | kg/m^2 | 30.9 (SD 5.6) | 32.5 (SD 5.7) | 31.7 (SD 5.65) |
| Baseline Estimated Glomerular Filtration Rate of Study Participants by Treatment Allocation | ml/min/1.73m^2 | 51 (SD 22) | 45 (SD 16) | 48 (SD 19) |
6. Primary Endpoint
The registry lists the primary outcome as Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks, measured over Baseline, 6 weeks, 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage change |
| Endpoint classification | Continuous Endpoint |
Flow-mediated vasodilation, abbreviated FMD in the registry record, was measured using high resolution ultrasound on the brachial artery. The recorded method defines FMD as the maximal percentage change in vessel size during hyperemia. The primary outcome is mean percentage change in FMD over 12 weeks, with measurements described at baseline, 6 weeks, and 12 weeks.
As a general statistical concept, a continuous endpoint retains information about the magnitude of a measured response rather than reducing it to categories such as improved or not improved. A mean summarizes the central level of a continuous measure for a group. The interpretation depends on the measurement procedure, the analysis population, and how observations over time are handled.
FMD was selected as a measure of endothelial function in this trial, as reflected in the endpoint title and trial summary. The registry description says mean changes between the listed time points, with 95% confidence intervals, were calculated using a linear mixed effects model. It does not give further model specifications, such as the exact contrast or covariance structure. The endpoint therefore indicates what was measured and the reported group summaries, but it does not by itself provide a direct estimate of the difference between treatment and placebo.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is a continuous group-level measure. For treatment, the reported mean percentage change is 1.1, with a 95% confidence interval from -0.1 to 2.3. For placebos, it is 0.3, with a 95% confidence interval from -0.9 to 1.5. The registry record presents these as group estimates for the primary endpoint. It does not report a between-group contrast, its confidence interval, or a test result in the registry record.
A confidence interval describes statistical uncertainty around an estimate under the assumptions of the method used. In general, it gives a range of values that are compatible with the data and model at the stated confidence level. It is not a guarantee that the true value lies within the interval, and it does not show the probability that the effect is beneficial. The intervals reported for each group should not be treated as a substitute for an interval around the treatment-versus-placebo contrast.
The group intervals extend from negative to positive values. This means the group summaries do not pin down a direction of mean change with high precision relative to zero. However, a comparison between groups requires a direct estimate that accounts for the trial’s analysis. Judging a comparative result from group means or the appearance of their separate intervals can be misleading. The registry record does not report the comparative estimate needed to state how large the difference was or how precisely it was estimated.
The endpoint description says that changes across baseline, 6 weeks, and 12 weeks were calculated with a linear mixed effects model. The posted arm summaries alone do not reveal the model’s full specification or the handling of incomplete measurements. Nor do they indicate whether the group values correspond to a particular time-point contrast or to another model-based summary beyond the stated mean changes over 12 weeks.
Thus, the posted data describe estimates for each arm and their confidence intervals, but the registry record does not provide enough information to draw a complete comparative statistical conclusion. The absence of a reported comparison is not evidence that the arms were equivalent, and it is not evidence that they differed. Equivalence or a meaningful difference would require a defined comparative estimand, an estimate, and suitable uncertainty information. No clinical threshold for interpreting the size of the FMD change is reported in the registry record.
The trial summary states that the study was intended to test safety and efficacy of combination therapy on endothelial function and inflammation. That stated purpose is not itself a result. The primary outcome values describe the posted FMD summaries only. Secondary outcome results, including the listed biomarker outcomes, are not reported in the registry record for this analysis, so no interpretation of their estimates is possible.
9. Statistical Methods Explained
The primary outcome is continuous: it is a mean percentage change in FMD. Continuous outcomes can preserve gradations in measured responses. In general, their analysis depends on the scale of measurement, the distribution of observations, the study design, and the target comparison. The registry describes FMD as the maximal percentage change in vessel size during hyperemia, assessed with high resolution ultrasound on the brachial artery. It lists measurement at baseline, 6 weeks, and 12 weeks.
What does the mean summarize?
A mean is a measure of the center of a set of values. It does not describe every participant’s response, the spread of individual values, or the shape of the observed distribution. A group mean can be useful for summarizing a continuous endpoint, but readers should not assume that participants had similar responses or that the mean represents each participant. The registry record reports arm means and confidence intervals, but does not report a measure of between-participant variability in the posted primary outcome details.
What does the confidence interval communicate?
In general, a confidence interval expresses uncertainty in an estimate under a statistical model and its assumptions. A narrower interval indicates greater precision for that estimate, while a wider interval indicates greater uncertainty. The reported 95% confidence intervals accompany the treatment and placebo means: 1.1 with limits -0.1 and 2.3 for treatment, and 0.3 with limits -0.9 and 1.5 for placebos. They describe uncertainty for those reported group summaries. They are not the confidence interval for a treatment-versus-placebo effect, which is not reported in the registry record.
A confidence interval should be interpreted alongside the quantity it estimates. An interval for a within-arm change answers a different question from an interval for a difference between arms. The primary trial question is comparative, but the registry entries include arm-level values rather than a direct comparative estimate. The interval endpoints therefore do not supply the missing contrast or a formal test of that contrast.
Why use a mixed effects model?
The endpoint description says that mean changes between baseline, 6 weeks, and 12 weeks, with 95% confidence intervals, were calculated using a linear mixed effects model. As a general concept, mixed effects models can represent repeated measurements from the same participant while accounting for the fact that those observations may be related. Such models can estimate average patterns while allowing individual observations to contribute within a structured analysis.
That general description does not identify the exact model used in this trial. The registry record does not report the fixed effects, random effects, covariance structure, missing-data assumptions, or precise contrast used to produce the posted means. It also does not state how deviations from model assumptions were assessed. These details matter because they can affect the estimand, standard errors, confidence intervals, and interpretation.
What is the role of the randomized design?
Randomization is intended to make the assigned groups comparable on average with respect to factors that could influence outcomes. Masking can reduce the influence of expectations on care, measurement, or assessment, depending on how it is implemented. These are general design principles, not evidence that all potential biases were eliminated in this trial. The registry record labels the study randomized and quadruple masked, but does not describe sequence generation, concealment, or masking procedures.
The parallel model means that the record describes treatment and placebo groups rather than a crossover comparison. The trial’s treatment regimen is immediate release sodium nitrite 40 mg by mouth twice per day and isoquercetin 225 mg by mouth once per day; the comparator received identical placebos. The design labels do not establish adherence or completeness of outcome measurements, details that are not reported in the registry record.
How should planning calculations be read?
In general, a sample-size calculation is a planning exercise based on assumptions about an effect, variability, allocation, and statistical error rates. It is not a measure of the probability that a completed study has detected a real effect. The planning illustration associated with this record is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; it is not the trial’s own design calculation. The stated fractions of the observed effect refer to planning scenarios, not observed outcomes.
Such illustrations should not be described as observed power. The record does not report the trial’s original sample-size justification or its planning assumptions. No conclusion about whether the trial was adequately sized for its intended question can be drawn from the planning description alone. The posted primary confidence intervals are the more direct indication of precision for the reported arm estimates, while the missing comparative estimate limits assessment of precision for the main contrast.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 21 outcome measures and 9 posted secondary outcomes. Those secondary outcomes include changes in endothelial function biomarkers, inflammatory biomarkers, and LDL. The registry entries available for this analysis do not report results for those outcomes. The record reports 0 analyses, so additional analysis details are not available in the registry record.
Multiplicity arises when a study makes several statistical comparisons or evaluates several outcomes. In general, testing many hypotheses can increase the chance of finding at least one apparently notable result by chance. Statistical plans may address that issue through a prespecified hierarchy, adjustment procedure, or careful distinction between primary and exploratory analyses. The registry record does not report a multiplicity adjustment, testing hierarchy, or statistical plan for the listed outcomes. It is therefore not possible to determine how multiplicity was handled.
The primary endpoint description identifies a linear mixed effects model, but does not report how missing FMD observations were handled. The registry record also does not describe imputation, sensitivity analyses, or assumptions about why measurements may be missing. These omissions matter because conclusions from repeated-measures analyses can depend on the amount and pattern of missing data and on the assumptions used to address it.
Analysis populations are not described in the registry record. The record does not state whether the reported results use an intention-to-treat, per-protocol, or other population, nor does it report participant flow or exclusions from analysis. These details are not reported in the registry record. Consequently, the reported means cannot be tied to a more specific analysis population from this information alone.
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 |
|---|---|---|---|
| Treatment | 1 | 35 | 2.9% |
| Placebos | 1 | 35 | 2.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment | 0 of 35 |
| Placebos | 0 of 35 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1.75% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment | 11 of 35 |
| Placebos | 14 of 35 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment | Placebos |
|---|---|---|---|
| Serious Adverse Event - Inpatient hospitalization | Cardiac disorders | 1 of 35 | 1 of 35 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment | Placebos |
|---|---|---|---|
| Adverse Events | Cardiac disorders | 11 of 35 | 14 of 35 |
Serious events with the highest arm-level rate: serious adverse event - inpatient hospitalization (2.9%).
The registry reports serious adverse events for the treatment and placebo groups. In each group, 35 participants were listed as at risk and 1 as affected by a serious adverse event. Deaths were reported as 0 in each group. The registry also reports other adverse events for 35 participants at risk in each group, with 11 affected in treatment and 14 affected in placebo. These are descriptive counts in the record, not a comparative statistical analysis.
The listed serious adverse event term is Serious Adverse Event - Inpatient hospitalization, reported as 2.9%. The registry record does not provide further detail in the registry record about the event’s nature, timing, relationship to treatment, or whether the listed term accounts for all serious adverse events. A serious adverse event classification should not be confused with a judgment that an event was caused by a study intervention.
Counts alone do not show whether a difference between groups is meaningful or attributable to treatment. Interpretation depends on event definitions, follow-up, completeness of reporting, and the uncertainty around any comparative estimate. A comparative safety estimate and its uncertainty are not reported in the registry record. These figures describe what was posted; they do not establish a safety conclusion.
12. What the Result Does, and Does Not, Mean
The record describes a completed randomized, quadruple-masked, parallel phase 2 trial of immediate release sodium nitrite plus isoquercetin versus identical placebos in patients with chronic kidney disease. Its primary outcome was mean percentage change in FMD over 12 weeks. The posted arm means are 1.1 for treatment and 0.3 for placebos, with respective 95% confidence intervals from -0.1 to 2.3 and from -0.9 to 1.5.
These estimates show the reported group summaries and the uncertainty attached to each. They do not provide a direct estimate of the treatment-versus-placebo difference. Without that comparative estimate and its confidence interval or test, the magnitude and precision of the primary between-group contrast are not reported in the registry record. The posted values therefore should not be used to claim either a comparative benefit or a lack of difference.
The outcome is a measurement of endothelial function as described by the trial, not a direct report of a clinical event or an individual participant’s experience. The registry entries do not establish how a change in this measure relates to outcomes that matter to patients, and no threshold for interpreting clinical importance is reported in the registry record. The listed biomarker outcomes are secondary measures; their results are not reported in the registry entries.
The safety figures are also descriptive. Serious adverse events were reported for 1 participant in each group, while deaths were 0 in each group. Other adverse events were reported for 11 participants in treatment and 14 in placebo. These counts do not establish causality or a statistically supported difference between the groups.
The result should be read as a limited account of the posted endpoint summaries and adverse-event counts. It does not resolve the trial’s full comparative efficacy or safety question. The record lacks several details needed for fuller interpretation, including a direct primary contrast, analysis-population information, missing-data methods, and a reported statistical plan.
13. Why This Trial Matters Statistically
This trial illustrates the distinction between reporting an outcome for each randomized group and reporting the comparison that randomization is designed to inform. The posted FMD means and confidence intervals describe treatment and placebo separately. A comparative estimate is needed to quantify the difference between the assigned groups and its uncertainty. Without it, group summaries cannot fully answer the primary comparative question.
The record also illustrates why a confidence interval must be linked to its estimand. The intervals around each arm’s mean describe uncertainty for those arm-level summaries. They do not directly express uncertainty around the difference between groups. Statistical interpretation depends not only on the numerical values but on the quantity estimated and the method used to estimate it.
Repeated measurements are another important feature. FMD was assessed at baseline, 6 weeks, and 12 weeks, and the registry says a linear mixed effects model was used. In general, such models can account for correlation among repeated observations, but interpretation relies on details of model specification and handling of incomplete data. Those details are not reported in the registry record, making it important to distinguish the named method from a fully described analysis.
The trial’s outcome list includes measures from several biomarker domains, while the registry entries report 9 posted secondary outcomes and no posted analysis details. This highlights the importance of prespecified outcome priorities and multiplicity plans when studies examine multiple endpoints. The registry record does not report those plans, so the scope and status of secondary analyses cannot be assessed from these registry entries.
Finally, the sample-size description is explicitly a planning illustration based on the observed effect, rather than the trial’s own design calculation. Treating it as observed power would confuse a retrospective planning exercise with the information conveyed by the estimates and their uncertainty. The record’s limitations demonstrate why precise reporting of contrasts, analysis populations, missing-data handling, and statistical plans is central to transparent interpretation.
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 limitation for interpreting the primary outcome is that the registry record reports arm-level means and confidence intervals but does not report a direct treatment-versus-placebo estimate. Without that contrast, the comparative magnitude and precision of the primary result cannot be stated. A formal test result is also not reported in the registry record for this analysis.
The endpoint description says a linear mixed effects model was used, but the model specification is not reported. The record does not state the exact contrast represented by the posted means, the covariance structure, the analysis population, or the handling of missing observations. These omissions constrain assessment of whether the reported summaries align with the intended primary question and how robust they are to analytic choices.
The record lists secondary outcome measures, but the registry entries do not include their results or a multiplicity plan. The record also does not report a protocol-level statistical analysis plan or the original sample-size justification. The planning illustration is described as based on the observed effect and is not the trial’s own design calculation.
The registry entries do not provide detailed participant characteristics, eligibility criteria, recruitment flow, adherence, or the implementation of masking and randomization. They also do not describe the timing, nature, or treatment relationship of adverse events beyond the posted summary terms. These limitations do not negate the reported results, but they narrow what can be inferred from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial — NCT02552888.
- Registry record last updated 2021-04-20; status last verified 2021-03.
- Results first posted 2021-04-20.
- 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 NICE Trial was a completed randomized, quadruple-masked, parallel phase 2 study sponsored by Tulane University. The registry record reports enrollment of 70, a start date of 2016-03, and primary completion in 2017-06. The study concerned patients with chronic kidney disease.
The treatment regimen was immediate release sodium nitrite 40 mg by mouth twice per day plus isoquercetin 225 mg by mouth once per day; the comparator received identical placebos. The primary outcome was mean percentage change in endothelium-dependent FMD over 12 weeks, measured at baseline, 6 weeks, and 12 weeks. The reported treatment mean was 1.1, with a 95% confidence interval from -0.1 to 2.3; the placebo mean was 0.3, with a 95% confidence interval from -0.9 to 1.5.
A direct between-group primary estimate, analysis-population details, missing-data methods, and a multiplicity plan are not reported in the registry record. Serious adverse events were reported for 1 participant in each group, and deaths were 0 in each group.