CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (NCT03998163), a na phase 3 study. The primary outcome is Number of Participants With AEs..

2. Clinical Question

The registry describes a multicenter study of CR845 in people receiving hemodialysis who had moderate-to-severe pruritus. Its primary outcome is the number of participants with adverse events, assessed by monitoring adverse events through the follow-up visit at Week 13-14. The intervention description specifies intravenous CR845 at 0.5 mcg/kg after each dialysis session; the arm description states that sessions occurred three times per week. The treatment period was up to 12 weeks.

This is a safety and effectiveness question framed within an open-label, single-group study. Because no comparator group is listed, the record does not describe a direct comparison with another treatment or with no study treatment. The posted adverse-event counts describe events recorded among participants in the CR845 group; they do not, on their own, distinguish effects of treatment from events that might occur for other reasons.

The registry record does not report a separate effectiveness endpoint or an effectiveness result. It lists one outcome measure and no analyses. Details of how effectiveness was defined or assessed are not reported in the registry record. Accordingly, the primary question that can be addressed from the posted outcome information is descriptive: what adverse-event counts were recorded in the study group over the specified period?

3. Trial Design

This was a Phase 3, multicenter, open-label study with a single group. The registry lists 222 participants as enrolled and identifies the study as completed. The study start date is 2019-05-06, and the primary completion date is 2020-02-26. Cara Therapeutics, Inc. is listed as the sponsor.

The study intervention was CR845 0.5 mcg/kg given intravenously after each dialysis session. The arm description specifies administration three times per week. The brief summary describes an up to 12-week treatment period, and the primary outcome timeframe extends through the follow-up visit at Week 13-14. The registry does not report the actual treatment duration for individual participants.

Allocation is listed as not applicable, and masking is listed as none. In practical terms, the record describes participants receiving the study intervention without a listed randomized assignment or masking. No control arm is listed. This design can report what was observed among the participants treated in the study, but it does not provide a concurrent group for estimating how outcomes would have differed without CR845 or under another intervention.

The registry record does not report the number or location of study centers, eligibility criteria beyond the stated population, details of the treatment administration process beyond the dose and schedule, or a protocol-based sample-size justification. It also does not report interim analyses or a detailed statistical analysis plan. These details should not be inferred from the Phase 3 designation or from the fact that the study is completed.

The record lists one outcome measure and zero analyses. The adverse-event summary reports serious and other adverse-event counts for the CR845 group. The record does not describe a randomized comparison, and its listed design should not be read as if it were a like-for-like controlled trial.

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

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 Number of Participants With AEs., measured over Up to Follow-Up Visit (Week 13-14).

The primary outcome is the number of participants with adverse events, measured through the follow-up visit at Week 13-14. The registry says adverse events were assessed by monitoring. The outcome is expressed as a count of participants, rather than as a measure of symptom severity or a rate over person-time.

Counting participants with events is a straightforward way to describe how many people in a study group experienced events during the observation period. It can provide a basic account of safety experience. A participant count does not, by itself, describe how many separate events each participant experienced, how long events lasted, or their severity. Those details are not reported for the overall primary outcome in the registry record.

The posted adverse-event information distinguishes serious adverse events from other adverse events and gives the number of participants affected in each category. It reports 45 participants with serious adverse events and 11 with other adverse events, each among 222 at risk. The record does not separately report an overall count of participants with any adverse event, so these category counts should not be combined or treated as an overall total. The registry record also does not provide a definition of the event categories beyond labeling them serious and other.

General: participant counts are useful for communicating how many people were affected, but they do not establish that the study intervention caused an event. In a single-group study, a count is descriptive of what was recorded during follow-up; causal attribution requires additional evidence and cannot be inferred from the count alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of evidence does the design provide?

The registry describes an open-label, single-group study with no listed comparator. General: a single-group study follows participants receiving an intervention and records outcomes in that group. Its results can characterize what was observed during the study, but a change or event count cannot be compared with what would have happened under a different intervention unless a suitable comparison is available. In this record, no randomized comparison is listed.

Open-label means masking is listed as none. General: when treatment assignment is known, expectations or awareness can affect some aspects of care, event reporting, and outcome assessment. The extent to which this matters depends on the outcome and how it is collected. The registry says adverse events were monitored, but additional details about monitoring procedures are not reported in the registry record.

How should participant counts be read?

The primary outcome is a count of participants with adverse events. The posted safety summary reports 45 participants with serious adverse events and 11 with other adverse events, among 222 at risk in each category. These are participant counts, not counts of every event episode. General: if one participant experiences more than one event, the number of event episodes can exceed the number of participants affected. The registry record does not provide the total number of event episodes or explain overlap between the serious and other categories.

The record lists deaths separately, with a count of 3. It does not provide a time-to-event analysis, causes, or an assessment of relationship to treatment. General: a count alone does not convey when events occurred or how follow-up time differed across participants. The registry does not report participant-level follow-up duration or an event-rate analysis.

What does a confidence interval add?

General: a confidence interval is an uncertainty range calculated from data using a specified method. It helps show how imprecise an estimate may be, beyond stating the observed count. A confidence interval does not correct for the absence of a comparator, guarantee that a method's assumptions hold, or show that an intervention caused an outcome. No confidence intervals for the posted adverse-event counts are reported in the registry record.

The distinction between an observed count and an estimated rate is also important. A participant count describes how many people were recorded with an event. A rate requires an appropriate time denominator, such as person-time, and an analysis method suited to that denominator. The registry does not report person-time or event rates. No rates should be inferred from the participant counts.

What can be inferred from the event-term percentages?

The registry lists percentages for selected serious adverse-event terms: Hyperkalaemia, Clostridium difficile colitis, Sepsis, Arteriovenous fistula thrombosis, Syncope, and Anaemia. General: event terms describe types of events, while participant-level counts describe how many people were affected. The two are not interchangeable, and a participant may be represented by more than one event term. The record does not report term-specific counts or explain whether the list is exhaustive. The percentages are therefore best read as the registry’s descriptions of listed terms, not as a full distribution or as comparative risks.

What is not available about statistical analysis?

The registry lists zero analyses. It does not report an inferential statistical plan, analysis population, missing-data method, or adjustment for covariates. It also does not report interim analyses or a sample-size justification. These omissions mean that a reader cannot assess which analysis decisions were prespecified, how missing observations were handled, or whether a particular population was used for each outcome.

General: analysis choices can influence estimates and their uncertainty. An analysis population defines which participants contribute to a result; a missing-data method specifies how absent outcome information is treated. Without those details, the posted counts can be described as recorded counts, but the handling of incomplete data cannot be evaluated from the registry record.

The record’s sample-size planning assumptions are described as an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. That illustration is not the trial’s own design: this study is listed as single-group, and the registry does not report a sample-size justification for its enrollment. Planning calculations are not observed power and do not add evidence about the outcomes actually recorded.

How does multiplicity fit into interpretation?

General: multiplicity arises when multiple outcomes, comparisons, or analyses are tested, because repeated testing can increase the chance of a result appearing notable by chance. The registry lists one outcome measure and no analyses, but it does not report a multiplicity plan or whether other outcomes or analyses were prespecified elsewhere. The absence of a reported plan should not be interpreted as proof that no additional analyses took place.

Overall, the methods information supports a limited descriptive interpretation. It identifies the study group, intervention, outcome timeframe, and posted safety counts. It does not provide the inferential details needed to evaluate comparative effects, uncertainty intervals, missingness, or analysis choices.

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("CR845 0.5mcg/kg")
n      <- c(222)
events <- c(143)
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  CR845 0.5mcg/kg  222  143  64.4  57.7  70.7  57.9  70.4  57.9  70.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the number of participants with adverse events, and no analyses. It does not report a multiplicity-adjustment plan, a hierarchy of outcomes, or whether additional outcomes or analyses were prespecified. General: multiplicity is relevant when several hypotheses or outcomes are evaluated, because repeated testing can make apparently notable results more likely by chance. The available record is not enough to determine how multiplicity was handled across any analyses outside the listed outcome.

Missing-data handling is not reported in the registry record. The record does not state how many participants completed follow-up, whether any adverse-event information was missing, how incomplete follow-up was treated, or whether participants with missing information were included in the outcome counts. The number enrolled should not automatically be treated as the number with complete outcome data, even though the adverse-event summary lists 222 at risk in each category.

The analysis populations are not reported in the registry record. It is therefore unclear whether the posted counts use all enrolled participants, all participants who received treatment, or another defined group. No sensitivity analyses addressing missing data are listed.

These gaps affect interpretation of the reported counts and make it difficult to assess potential bias from incomplete information. General: a missing-data approach cannot recover information that was never observed without assumptions; different assumptions can lead to different estimates. Because the registry does not describe the missingness or its handling, the possible influence on the posted results cannot be quantified from this record.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hyperkalaemia (2.3%), clostridium difficile colitis (1.4%), sepsis (1.4%), arteriovenous fistula thrombosis (1.4%), syncope (1.4%).

The registry reports 45 participants with serious adverse events among 222 at risk, 11 participants with other adverse events among 222 at risk, and 3 deaths. The serious-event terms listed include Hyperkalaemia (2.3%), Clostridium difficile colitis (1.4%), Sepsis (1.4%), Arteriovenous fistula thrombosis (1.4%), Syncope (1.4%), and Anaemia (0.9%). These figures describe the CR845 group during the study; they are not a comparison with another group.

The registry does not state whether serious and other adverse-event categories are mutually exclusive. The counts should not be added to produce a total number of participants with any adverse event. The record also does not report the overall number of participants with any adverse event as a separate result, the total number of event episodes, or term-specific participant counts. Percentages for event terms should be understood as the listed registry values; their denominator and selection process are not described in the record.

The death count does not establish that CR845 caused the deaths. The registry record does not report their causes, timing, or relationship to treatment. More generally, adverse events observed during a study are not automatically adverse reactions caused by the intervention. With no comparator group listed, these counts cannot quantify how event occurrence differed from another treatment or from no study intervention.

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

The record establishes that a completed, open-label, single-group study enrolled 222 hemodialysis patients with moderate-to-severe pruritus and evaluated intravenous CR845 at 0.5 mcg/kg after dialysis sessions. The stated treatment period was up to 12 weeks, and the primary outcome timeframe extended through the Week 13-14 follow-up visit. The posted safety information includes counts for serious and other adverse events and a separate death count.

Those data describe what the registry reports for the study group. They do not establish that CR845 caused any particular event, nor do they estimate how event occurrence would compare under a different treatment. The lack of a listed comparator is central: differences between this group and an imagined alternative group cannot be calculated from the posted results.

The record also does not report a separate effectiveness result. Although the study title and summary refer to safety and effectiveness, the listed outcome measure is the number of participants with adverse events. The registry record does not describe an effectiveness outcome or its analysis. No conclusion about effectiveness should be drawn from the adverse-event counts.

The available information has additional limits. The registry lists no analyses and does not report confidence intervals, missing-data handling, or analysis populations. These omissions prevent a full assessment of statistical uncertainty and of how incomplete outcome information may have been handled. Event-term percentages are listed, but term-specific counts and the denominator are not reported.

General: statistical significance, causal attribution, and clinical importance are different questions. Statistical methods can describe uncertainty under assumptions; they cannot supply a missing comparison or turn an observed association into proof of cause. The posted results are therefore most appropriately read as descriptive safety information from one study group, with important limits on comparative and causal interpretation.

14. Why This Trial Matters Statistically

This study is statistically notable for the kind of question its design can answer. A single-group, open-label study can document adverse events observed among participants receiving an intervention and can provide descriptive information about the study experience. The registry’s counts and listed serious-event terms offer that form of description for CR845 in the enrolled population.

At the same time, the absence of a listed comparator constrains the inference. A count among treated participants does not show whether the same events would have been more or less common under another treatment or without the study intervention. This distinction is especially important for safety outcomes, which may occur during follow-up without being caused by the intervention. A concurrent comparison can help address comparative questions; this record does not list one.

The record also illustrates why outcome definitions and analysis details matter. The primary outcome is framed as a count of participants with adverse events, while the posted safety summary separates serious from other events and reports deaths separately. The registry does not describe overlap between categories or provide an overall count of participants with any adverse event. Readers therefore need to preserve these distinctions rather than combine figures into a broader result that the record does not state.

Finally, the absence of reported analyses, uncertainty intervals, missing-data methods, and analysis populations limits evaluation of precision and robustness. General: transparent reporting of these elements helps readers understand how estimates were produced and how much confidence to place in them. The registry record supports a cautious descriptive reading, while leaving comparative safety and effectiveness questions unresolved.

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 main trial-specific limitation is the single-group design. No comparator is listed, so the registry results cannot directly estimate differences in adverse events relative to another intervention or a control condition. The study is also open-label, with masking listed as none. The extent to which awareness of treatment may have affected event reporting or assessment is not reported in the registry record.

The posted outcome information is limited. The primary endpoint is the number of participants with adverse events, but the record separately reports serious and other adverse-event counts without stating whether these categories overlap. It does not give a distinct overall count of participants with any adverse event. The registry lists selected serious-event terms and percentages but does not report term-specific participant counts or explain the denominator and selection process.

The record reports 3 deaths but does not provide their causes, timing, or relationship to treatment. It does not report event duration, recurrence, or the total number of event episodes. The actual treatment duration and follow-up completeness for individual participants are not reported in the registry record.

Statistical reporting is also limited: no analyses are listed, and the registry does not report confidence intervals, a statistical analysis plan, analysis populations, missing-data methods, interim analyses, or a sample-size justification. These omissions restrict assessment of precision, missingness, and analysis choices. The registry also does not report a separate effectiveness endpoint or result, despite the study description referring to effectiveness. These limitations apply to interpretation of the registry record and do not establish what may have been reported elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus — NCT03998163.
• Registry record last updated 2021-10-15; status last verified 2021-09.
• Results first posted 2021-10-15.
• 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

NCT03998163 is a completed Phase 3, multicenter, open-label, single-group study sponsored by Cara Therapeutics, Inc. It enrolled 222 hemodialysis patients with moderate-to-severe pruritus and evaluated intravenous CR845 at 0.5 mcg/kg after each dialysis session, described as three times per week. The treatment period was up to 12 weeks.

The primary outcome was the number of participants with adverse events through the follow-up visit at Week 13-14. The registry reports 45 participants with serious adverse events and 11 with other adverse events, each among 222 at risk, as well as 3 deaths. It lists selected serious-event terms with percentages. No analyses are listed, and no comparator group is described.

The record does not report a separate effectiveness result, confidence intervals, missing-data methods, analysis populations, or a sample-size justification. Its safety figures are descriptive observations from the study group, not estimates of comparative effects or proof that the intervention caused an event.