Preventing Sickle Cell Kidney Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preventing Sickle Cell Kidney Disease (NCT02373241), a randomized phase 2 study. The primary outcome is Feasibility as Measured by the Number of Patients That Accept Enrollment, Remain Adherent to Losartan, and Remain Adherent to Study Procedures..

2. Clinical Question

The clinical rationale described in the registry is that hypertension and renal injury are concerns in sickle cell disease, and that blood-pressure patterns across a 24 hour period may provide information beyond clinic measurements. The proposed feasibility study focused on abnormal nocturnal dipping. A separate prospective cohort was intended to track hypertension and potential markers of kidney injury and hypertension; that cohort should not be confused with the randomized treatment comparison.

The registry record reports the trial as terminated and enrollment as 1. It does not report a comparative estimate for the two blood-pressure targets. The study question is therefore best understood as a feasibility question whose posted results are too limited to characterize a treatment-target contrast.

3. Trial Design

The registry describes a randomized, parallel-group, unmasked Phase 2 study. Its randomized component compared two blood-pressure management targets, with losartan used in both arms. Participants were to start at 25mg daily, and the targets were in-clinic blood pressure <95th percentile in the standard arm and <75th percentile in the experimental arm. The registry does not report further details about the randomization procedure or allocation concealment.

The trial was presented as a feasibility study among adolescents with HbSS or SB0 thalassemia and abnormal nocturnal blood-pressure dipping. The brief description refers to a six month feasibility trial. The primary endpoint description also discusses adherence during a three year trial and gives an intended participant count of n=40 for that adherence assessment. The registry's primary outcome timeframe is listed as 5 yrs. These durations appear in different parts of the record, and their relationship is not explained.

A prospective cohort was also described, with participants aged 6-19 years. Its purpose was to evaluate hypertension incidence and potential biomarkers of kidney injury and hypertension. It planned annual evaluations, including 24 hour blood-pressure monitoring for participants aged 11 years or older and clinic blood pressure for all cohort participants. The registry does not report cohort results or clarify how cohort enrollment related to the randomized trial.

The record lists enrollment of 1 and status as terminated. It also states that the randomized trial was stopped because eGFR was determined not to be an accurate measure of GFR in patients with sickle cell disease. The record does not report the timing or operational consequences of that decision beyond the termination status. Although the trial is labeled randomized, the posted arm counts are 0 for standard management and 1 for experimental management, so the record does not show a substantial randomized comparison.

Masking is listed as none. There is no placebo arm described: both groups received losartan and differed in the target for in-clinic blood pressure. Further information about treatment titration, adherence measurement, eligibility exclusions, or the detailed conduct of follow-up is 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: We stopped the RCT as eGFR was determined not to be an accurate measure of GFR in SCD patients

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: 1 patient identified as eligible for the study due to ambulatory hypertension

6. Primary Endpoint

The registry lists the primary outcome as Feasibility as Measured by the Number of Patients That Accept Enrollment, Remain Adherent to Losartan, and Remain Adherent to Study Procedures., measured over 5 yrs.

The primary endpoint is a count of participants who accept enrollment, remain adherent to losartan, and remain adherent to study procedures. Its stated timeframe is 5 yrs. The description breaks the feasibility aims into acceptance and reasons for acceptance or rejection, adherence to losartan, and adherence to study procedures. These components address whether a randomized study of losartan could recruit and retain participants and whether participants could follow the assigned treatment and study requirements.

Feasibility outcomes are used to assess whether a study process can be carried out; they are not, by themselves, estimates of clinical benefit. Here, the endpoint is expressed as a number of participants rather than a rate or a between-arm treatment effect. While the description mentions acceptance and adherence, the registry does not post separate results for each component, a definition of adherence, or an account of how the components were combined in the reported count.

The record lists a primary result of 0 participants in the standard blood-pressure management arm and 1 in the experimental arm. These counts do not establish how many people met each element of the endpoint or whether the result represents completed follow-up. The record reports total enrollment of 1, but does not provide a detailed participant-level account linking enrollment, adherence, and endpoint ascertainment.

The broader study description also refers to safety and restoration of normal circadian blood pressure. Those aims do not change the meaning of the posted primary count. A count tied to feasibility can describe participation in the study, but it cannot establish whether the two blood-pressure targets differ in effect. The registry does not report a primary comparative analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish a descriptive result from evidence about a difference between treatment strategies. In this trial, the primary outcome is a count of participants meeting a feasibility description. The posted arm values are counts, and the registry does not report an analysis comparing them. The information supports a factual description of recorded enrollment and outcome counts, but not an estimate of the size or precision of a treatment-target effect.

What does randomization contribute?

In general, random allocation is used to make comparison groups similar, on average, with respect to factors that could affect outcomes. This supports interpretation of an observed group contrast as an effect of assignment, provided the trial has enough participants, outcome information is collected appropriately, and the analysis follows a suitable plan. Randomization does not make a comparison informative when there is almost no group-level outcome information. With enrollment of 1 and posted arm counts of 0 and 1, the registry does not contain a usable comparison of the two strategies.

The study is described as parallel and unmasked. In a parallel design, participants are assigned to one strategy rather than switching between strategies as part of the stated design. Unmasked means the registry does not list masking. The record does not describe the random sequence generation, concealment procedures, or any other steps used to implement randomization. Those details are not reported in the registry record.

How should a count endpoint be understood?

A count records how many participants meet a defined criterion. It is different from a proportion, which relates that count to a denominator, and from a rate, which also accounts for time at risk. The posted primary endpoint is described as a count of participants accepting enrollment and remaining adherent to medication and study procedures. The registry provides arm-level values but does not separately report the number meeting each endpoint component, the denominator used for any adherence calculation, or the length of observed follow-up for each participant.

In general, counts can be analyzed with methods appropriate to count outcomes, but the choice depends on the outcome definition, the observation process, and the analysis plan. Over-dispersion is a general concern when counts vary more than a chosen probability model expects; it can lead to uncertainty estimates that are too narrow if ignored. That issue cannot be assessed for this trial from the posted count alone. The record does not report a model, dispersion estimate, or analysis of the primary count.

What can a confidence interval say?

In general, a confidence interval expresses the uncertainty around an estimate under a statistical model and its assumptions. A narrow interval indicates greater precision than a wide interval, while both the interval and its interpretation depend on the data and method used. The registry does not report a confidence interval for the primary endpoint or a between-arm contrast. No precision estimate can therefore be described for the treatment comparison. A raw count alone does not supply the missing uncertainty information.

Similarly, a p-value is not a measure of effect size or clinical importance. It is a quantity generated by a specified statistical test under a null hypothesis and its assumptions. The registry reports no p-value or test for these outcomes. A reader should not infer statistical significance or non-significance from the absence of a reported test.

What do the planning illustrations represent?

In general, sample-size planning asks how many participants may be required to detect a specified effect under chosen assumptions. A planning illustration based on an observed effect is not the same as the original trial's sample-size justification and does not describe observed power. The record does not report the trial's own sample-size justification. It mentions n=40 in the adherence aim, but does not explain the basis for that planned count. The registry record's enrollment of 1 is an observed enrollment figure, not a planning target.

Sample-size calculations also rely on assumptions about allocation, outcome variability, and the effect to be detected. If those assumptions do not match the actual trial, the resulting illustration may not describe the study as conducted. Where an outcome is a count, the relevant model and dispersion assumptions matter. No planning calculation can compensate for the absence of a comparative dataset in the posted results.

What can be learned from the safety counts?

Safety results are reported as the number at risk and the number with events for each arm. These denominators matter because a count of events has meaning only in relation to how many participants were observed and the period of observation. The experimental arm lists 1 participant at risk, while the standard arm lists 0. With no participants listed at risk in the standard arm, a comparison of event frequencies is not possible from these entries. The record does not report exposure time or additional safety analysis.

More broadly, the registry lists no posted analyses. It does not report a prespecified statistical plan, model details, interim analyses, adjusted analyses, or a defined analysis population. These omissions limit the reader to descriptive interpretation of the recorded counts and design information. They do not justify reconstructing an analysis that the registry does not report.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Experimental Blood Pressure Management")
n      <- c(1)
events <- c(1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Experimental Blood Pressure Management  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two secondary outcomes: the number of patients with incident hypertension and feasibility measured by the number of patients with improvement in nocturnal blood pressure while receiving losartan. It does not report results for these secondary outcomes. The primary endpoint description itself includes acceptance, adherence to losartan, and adherence to study procedures, but separate component results are not reported.

When a study assesses multiple outcomes, multiplicity can arise because repeated tests increase the chance of at least one apparently notable result under a null model. In general, investigators may address this through a hierarchy of outcomes, adjusted thresholds, or a prespecified interpretation plan. The registry record does not report whether any multiplicity approach was planned or used. It also does not report a statistical analysis plan or any posted analyses.

Missing-data methods are not described. The record does not state whether participants were lost to follow-up, whether any outcome measurements were unavailable, or how missing observations would be handled. The recorded enrollment of 1 and termination status mean that a detailed account of follow-up and endpoint ascertainment is important, but it is not reported in the registry record.

The record also does not define analysis populations, such as whether any planned analysis was to include all randomized participants or only those completing follow-up. It gives no account of protocol deviations, treatment discontinuation, or the treatment of participants with incomplete adherence information. These details should not be inferred from the arm counts.

Finally, the trial description includes multiple time horizons: a six month feasibility trial in the brief summary, a three year adherence description, and a primary outcome timeframe of 5 yrs. The registry does not explain how these periods relate or which duration governed each analysis. Together with the absent analysis plan and missing-data description, this limits interpretation of both feasibility and secondary outcomes.

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 0% reporting threshold.

The registry's serious adverse event entries list the number of participants at risk, the number affected by serious events, and deaths. The standard blood-pressure management group has 0 listed at risk, 0 serious adverse events, and 0 deaths. The experimental blood-pressure management group has 1 listed at risk, 0 serious adverse events, and 0 deaths. Other adverse-event counts are also listed as 0 in each group.

These entries are counts, not estimates of risk. The group sizes are too limited for a meaningful comparison, and the standard group has no participant listed at risk. The registry does not report exposure duration or a safety analysis that accounts for follow-up. Therefore, the zero event counts should be understood only as the events recorded in this limited registry entry, not as evidence that an event could not occur or that the strategies have equivalent safety.

The record does not list top serious adverse-event terms. That absence does not add information about event types beyond the zero serious-event counts. The safety entries should be interpreted alongside the overall enrollment of 1 and the terminated status, rather than as a definitive assessment of comparative safety.

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

The registry record documents a randomized feasibility study of two losartan blood-pressure targets in sickle cell disease and describes a separate prospective cohort. It reports that the study was terminated and that enrollment was 1. The stated reason for stopping the randomized trial was that eGFR was determined not to be an accurate measure of GFR in patients with sickle cell disease. The record does not provide more detail about that determination or its implications for the study's endpoints.

The posted primary result is a count: 0 in the standard target arm and 1 in the experimental target arm. The endpoint was intended to cover acceptance and continued adherence to losartan and study procedures. The registry does not show separate results for these components or explain how the reported count maps to each criterion. Thus, the result does not give a complete account of recruitment, adherence, or reasons for participation decisions.

The counts do not establish whether the <75th percentile strategy differs from the <95th percentile strategy. There is no reported comparative estimate or measure of its precision. The record also does not post results for the secondary outcomes of incident hypertension or improvement in nocturnal blood pressure. No conclusion about clinical effectiveness should be drawn from these entries.

The safety data list no serious adverse events or deaths, but they cover only the small recorded study population and include 0 participants at risk in the standard arm. They cannot establish that either strategy is free of safety concerns or that the groups have similar safety outcomes.

The results are most useful as a limited record of study conduct: the trial was designed around feasibility and blood-pressure management targets, stopped, and enrolled 1 participant. They do not resolve the clinical or statistical questions the study was intended to investigate. Further information about outcome assessment, follow-up, analysis, and the cohort component is not reported in the registry record.

14. Why This Trial Matters Statistically

Feasibility is a central statistical concern when a study seeks to recruit and follow a specific population. The registry describes adolescents with HbSS or SB0 thalassemia and abnormal nocturnal blood-pressure dipping, and it identifies acceptance and adherence as primary feasibility concerns. These questions differ from estimating a treatment effect: even a well-designed clinical comparison depends on recruitment, retention, adherence, and usable outcome measurement.

The record also illustrates how outcome measurement can affect an entire research program. It states that the randomized trial was stopped because eGFR was determined not to be an accurate measure of GFR in patients with sickle cell disease. When a measure does not adequately represent the intended construct, an otherwise randomized comparison may not answer its intended question. The registry does not report further methodological detail, but the stated rationale highlights the need to consider measurement validity when choosing endpoints.

Statistically, the posted enrollment of 1 sharply limits what can be learned from the randomized component. Randomization is valuable for reducing bias in comparisons, but it cannot create precision in the absence of enough observed participants and outcomes. The available counts are descriptive and do not estimate the difference between blood-pressure targets.

The study also combined a feasibility trial with a planned cohort investigation. Those components address different questions and require different interpretations. The randomized trial focused on losartan targets and adherence, while the cohort was intended to examine hypertension and potential biomarkers. Separating these aims is important for understanding what the record does and does not establish.

Finally, the record's different stated timeframes and absent analysis details show why clear endpoint definitions and reporting of follow-up matter. Readers need to know when outcomes were assessed, how adherence was defined, and how incomplete observations were handled to interpret feasibility results. Those details are not reported in the registry record.

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 principal limitation is the very limited recorded enrollment: the registry reports 1 participant, with 0 in the standard arm and 1 in the experimental arm. This does not support a meaningful between-arm comparison. The record posts no comparative estimate, confidence interval, p-value, or statistical analysis for the primary outcome.

The primary endpoint combines acceptance, adherence to losartan, and adherence to study procedures in its description. The registry does not report these components separately, explain the operational definition of adherence, or clarify how the posted count corresponds to the endpoint criteria. This makes the count difficult to interpret beyond its basic descriptive meaning.

The trial is marked terminated, and the record attributes stopping to a determination about eGFR as a measure of GFR in sickle cell disease. The timing and consequences of this decision are not reported. The registry does not explain whether other outcome measures were collected, how the termination affected follow-up, or whether the planned cohort component continued.

Study duration is also unclear: the brief description refers to a six month feasibility trial, the primary endpoint description discusses a three year trial, and the primary outcome timeframe is listed as 5 yrs. The registry does not reconcile these descriptions. It also does not report a sample-size justification, missing-data approach, analysis population, or multiplicity plan.

The posted safety counts are limited, and no participant is listed at risk in the standard arm. This prevents a useful comparison of adverse events. Secondary outcomes are listed without posted results. Taken together, the registry record provides little information about clinical outcomes, precision, follow-up completeness, or the study's analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Preventing Sickle Cell Kidney Disease — NCT02373241.
• Registry record last updated 2024-04-03; status last verified 2024-04.
• Results first posted 2022-05-09.
• 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

The registry describes a randomized, parallel, unmasked Phase 2 feasibility trial comparing two losartan blood-pressure targets in adolescents with HbSS or SB0 thalassemia and abnormal nocturnal blood-pressure dipping. Both groups were to start losartan at 25mg daily, targeting in-clinic blood pressure <95th percentile or <75th percentile. A separate prospective cohort was also described.

The study is listed as terminated, with enrollment of 1. The record states that the randomized trial stopped because eGFR was determined not to be an accurate measure of GFR in patients with sickle cell disease. The primary endpoint concerns acceptance and adherence. Its posted arm counts are 0 for standard management and 1 for experimental management, with no comparative statistical analysis reported.

The registry lists two secondary outcomes, but does not post their results. Safety entries report no serious adverse events or deaths among the recorded participants. Given the limited enrollment and missing analysis details, the posted data are descriptive and do not estimate the comparative effects of the two treatment targets.