Utility of Hyperpolarized 13C-pyruvate Metabolic Magnetic Resonance Imaging: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Utility of Hyperpolarized 13C-pyruvate Metabolic Magnetic Resonance Imaging (NCT04698564), a na phase 2 study. The primary outcome is CTCAE v4.0 Higher Than Grade 2.

2. Clinical Question

The study asked whether hyperpolarized 13C-pyruvate metabolic MRI could be performed safely in men suspected of having prostate cancer. Its official title also places the imaging method in the context of diagnosis and risk-stratification, but the registry record reports no usable data from which diagnostic performance or risk-stratification can be assessed.

The clinical question therefore has two distinct parts: whether the procedure was completed with an acceptable safety profile, and whether the resulting scan was of sufficient quality for the intended diagnostic research. The posted results address only the event-count portion descriptively. They do not establish diagnostic accuracy, comparative utility, or the relationship between tissue metabolites and cancer diagnosis.

3. Trial Design

The registry describes a Phase 2, single-group study with no randomization and no masking. Allocation is listed as not applicable, consistent with the absence of a randomized comparator. The brief summary states that there would be no placebo treatment. The intervention is hyperpolarized 13C-pyruvate, and the study concerns metabolic MRI in men suspected of having prostate cancer; the arm description also includes people known to have prostate cancer.

The registry lists enrollment of 4 participants and identifies the study status as terminated. The listed study start is 2020-12-01, and the listed primary completion date is 2025-12-05. Those dates do not change the posted-results statement that the study ended prematurely. The registry does not report the reason for termination.

The single-arm structure is important to interpretation. Observations in this design cannot be compared against a concurrent randomized control group, and any secondary objective concerning standard MRI is not equivalent to a controlled head-to-head comparison. The stated secondary outcomes concern diagnostic accuracy, utility over standard MRI, and correlations between tissue metabolite concentrations and cancer diagnosis. The posted results do not provide usable data for those assessments.

The primary outcome is titled CTCAE v4.0 Higher Than Grade 2, with a timeframe of within three years post treatment. Its description also refers to successful scan completion and a minimum scan-quality standard measured by signal-to-noise ratio. The registry record does not report a detailed statistical analysis plan, participant flow beyond the information in the outcome description, or the planned analysis populations.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This study was terminated prematurely. No patients had treatment-related adverse events as assessed by CTCAE v4.0 higher than grade 2 until study termination. Four participants were enrolled; however, no usable data were obtained. * One withdrew before the visit * One could not complete the HP MRI due to pyruvate QC failure, so the HP scan was not completed. * Two patients completed scans, but the SNR was too low (below minimum quality standard) for analysis.

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 CTCAE v4.0 Higher Than Grade 2, measured over Within three years post treatment.

The primary endpoint is titled CTCAE v4.0 Higher Than Grade 2 and is expressed as a count of participants. CTCAE is the adverse-event grading system named in the registry. In general, an endpoint based on the number of participants meeting a stated adverse-event threshold is intended to describe how many people experienced an event meeting that definition during the specified observation period.

The registry gives the timeframe as within three years post treatment. Its description says the study would quantify participants with treatment-related adverse events assessed as CTCAE v4.0 higher than grade 2. It also says the study would determine the number who successfully completed a scan meeting a minimum quality standard, measured by signal-to-noise ratio. Thus, the description combines a safety count with a scan-completion and quality objective, although the outcome title emphasizes adverse events.

These measures serve different purposes. A safety count describes observed adverse events under the registry’s stated definition; scan completion and signal-to-noise ratio concern whether usable imaging was obtained. Both are relevant to a feasibility-oriented imaging study, but a count of adverse events cannot establish diagnostic accuracy. The posted results state that no usable data were obtained, so the record does not report a scan-quality result or diagnostic endpoint estimate. It reports that no participants had treatment-related adverse events higher than grade 2 before termination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary measure is a count of participants meeting an adverse-event definition: CTCAE v4.0 higher than grade 2. Counts are a natural way to report how many people experienced a specified event. They are not interchangeable with a continuous measurement such as a laboratory value, and they do not by themselves describe how long participants were observed. The registry also mentions scan completion and a minimum quality standard based on signal-to-noise ratio, which are distinct from the adverse-event count.

What does a single-group study allow? A single-group study can describe observations made among participants who receive the intervention. General statistical principle: without a concurrent comparison group, the data do not estimate a contrast between intervention and control under randomized assignment. In this record, there was no randomization, placebo, or control arm. Consequently, the listed objective of assessing utility over standard MRI should not be read as a randomized comparison. The record does not report a comparative analysis using standard MRI.

Why does follow-up matter? Event counts depend on who was observed and for how long. General statistical principle: when follow-up differs across participants, a raw count can conceal differences in opportunity to observe an event. The stated timeframe is within three years post treatment, but the study terminated prematurely. The registry reports no treatment-related events above the stated threshold before termination and does not provide individual follow-up durations or a complete account of outcome ascertainment. Thus, the event count should be read in the context of incomplete study conduct, not as a completed assessment over the entire stated timeframe.

How should zero events be read? A reported count of zero means that no qualifying events were reported in the described observation. It does not prove that the underlying event probability is zero. General statistical principle: with limited or incomplete observation, zero observed events can leave broad uncertainty about what might be seen in a larger or more complete study. Confidence intervals are used to express uncertainty around an estimate; the registry record does not report a confidence interval for this outcome. No interval should be inferred from the posted counts without a defined analysis population and follow-up basis.

What is over-dispersion? General statistical principle: over-dispersion occurs when count outcomes vary more than a chosen statistical model expects. It can affect uncertainty estimates if a model assumes less variability than the data contain. The registry record reports no fitted count model or analysis, and no usable data were obtained. Over-dispersion therefore cannot be evaluated for this study from the posted results. This concept is not a reason to reinterpret the zero-event statement as an estimated treatment effect.

What do the safety counts represent? The registry’s adverse-event entry gives separate counts for participants at risk and affected by serious adverse events, participants at risk and affected by other adverse events, and deaths. Such entries are descriptive summaries. General statistical principle: a count should be interpreted alongside the definition of an event, the population in which it was sought, and the period of observation. The registry lists three at risk for each adverse-event category, but does not provide a detailed account of how those entries relate to all four enrollees or to the primary outcome’s full observation timeframe.

What analysis is available? The record lists zero analyses. It does not report an inferential method, model, adjustment strategy, missing-data method, or analysis population. No p-value, effect estimate, or confidence interval is posted. General statistical principle: a method cannot recover information that was not collected or made usable; a model fitted to no usable outcome data would not provide a study-based estimate. The registry’s descriptive statements are therefore the appropriate limit of interpretation.

What about planning calculations? Sample-size planning is distinct from observed results. General statistical principle: a planning illustration describes the size a future study might need under stated assumptions; it is not observed power and does not repair missing outcome data. The record does not report the trial’s own sample-size justification. No planning calculation can be interpreted as evidence about the intervention’s safety or diagnostic performance in this terminated study.

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("Single-arm Study in Patients Who Are Suspected or ")
n      <- c(3)
events <- c(0)
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  Single-arm Study in Patients Who Are Suspected or   3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry names secondary outcomes concerning accuracy of metabolic MRI for diagnosing prostate cancer, utility over standard MRI, and correlation of tissue metabolite concentrations with cancer diagnosis. It also lists four outcome measures overall and zero analyses. The posted results do not report estimates for these secondary objectives.

When a study evaluates multiple outcomes, multiplicity can matter because examining several hypotheses can increase the chance of at least one apparently notable result by chance. General statistical principle: approaches to multiplicity may include defining a primary hypothesis in advance or adjusting interpretation across related tests. The registry record does not report a multiplicity procedure, a hierarchy among secondary outcomes, or a detailed statistical analysis plan. With no analyses reported, there are no posted hypothesis tests to interpret for multiplicity.

Missing-data handling is also not reported in the registry record. The primary outcome description states that four participants were enrolled but no usable data were obtained. It identifies one participant who withdrew before the visit and one who could not complete the HP MRI. It does not detail the reasons usable data were unavailable for the others, whether any outcome data were collected for them, or whether the withdrawals and incomplete scan were handled under a prespecified rule.

The analysis populations are not reported in the registry record. In particular, the record does not state which participants were included in safety summaries, whether any participants contributed partial observations, or how the at-risk counts in the adverse-event entry were defined. These omissions prevent reconstruction of an analysis denominator or a complete participant-flow account. No assumption should be made that every enrolled participant had complete outcome assessment.

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 adverse-event entry lists three participants at risk for serious adverse events and zero affected, three participants at risk for other adverse events and zero affected, and zero deaths. The primary outcome description separately states that no patients had treatment-related adverse events assessed as CTCAE v4.0 higher than grade 2 until study termination. These are descriptive statements from the registry, and the record does not provide serious adverse-event terms.

The different counts should not be collapsed into a claim that all four enrollees completed safety follow-up. The primary outcome description reports premature termination and no usable data; it also notes one withdrawal before the visit and one inability to complete HP MRI. The safety entry’s at-risk group is three, while the enrollment is four, and the registry does not explain that difference. The record does not report individual follow-up duration or whether the at-risk population corresponds to complete observation over the stated timeframe.

General statistical principle: zero observed events describes what was recorded, not proof that the underlying risk is absent. A limited observation period, incomplete follow-up, or a small at-risk group can leave substantial uncertainty. The posted counts therefore support a narrow conclusion about reported events before termination, not a broad conclusion about safety under full follow-up or in a larger population.

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

The registry record documents a terminated single-group study of hyperpolarized 13C-pyruvate metabolic MRI in men suspected or known to have prostate cancer. Four participants were enrolled, the study was terminated prematurely, and the outcome description says no usable data were obtained. It also reports that no patients had treatment-related adverse events assessed as CTCAE v4.0 higher than grade 2 until termination. This is the extent of the direct result that can be described from the posted information.

The record does not show whether the method accurately diagnoses prostate cancer, whether it improves on standard MRI, or whether metabolic measurements correlate with cancer diagnosis. Those questions appear among the registered objectives, but no analyses are reported. There is also no reported scan-quality result, despite the primary-outcome description’s reference to scan completion and a minimum signal-to-noise standard.

The zero-event statement should not be interpreted as proof of no risk. The study did not reach a complete usable dataset, the registry notes incomplete participation for two enrollees, and the safety entry lists three participants at risk. The registry does not explain the full follow-up or the status of every participant’s data. A count observed before termination is not equivalent to a definitive estimate across the stated timeframe.

Likewise, termination and unavailable data do not establish that the imaging approach is ineffective. They mean that the posted results cannot answer the diagnostic and comparative questions. No treatment benefit, lack of benefit, or diagnostic performance conclusion follows from the record. The appropriate interpretation is limited: the study ended before usable outcome data were available, with no higher-than-grade-2 treatment-related adverse events reported before termination.

14. Why This Trial Matters Statistically

This record is statistically informative because it illustrates the difference between a registered research question and an answerable result. The study had a stated safety and imaging-quality objective and listed diagnostic and comparative secondary outcomes. However, termination and lack of usable data prevented those aims from producing estimable results in the posted record. A registered endpoint alone does not guarantee that an endpoint can be analyzed.

The study also shows why participant flow and denominator definitions matter. Enrollment is reported as four, while the safety entry lists three participants at risk. The outcome description identifies a withdrawal before the visit and inability to complete HP MRI, but does not account in detail for the remaining data status. Without clear follow-up and analysis-population information, even a simple count requires careful qualification.

Finally, zero observed events have a limited statistical meaning when the study ends early. General statistical principle: observed counts describe the recorded experience, while an estimate of risk requires an interpretable population and observation period. The registry’s safety statement is useful as a report of what was observed before termination, but it cannot substitute for complete outcome collection or answer the imaging-performance questions.

For researchers, the key lesson is not a conclusion about clinical utility. It is the importance of distinguishing feasibility, safety, scan quality, diagnostic accuracy, and comparison with usual imaging as separate questions, each requiring usable data and a clearly described analysis. In this record, those analyses are not reported.

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 most consequential limitation is explicit in the registry: the study was terminated prematurely and no usable data were obtained. The record therefore does not support estimates for diagnostic accuracy, comparison with standard MRI, tissue-metabolite correlations, or scan quality. It also does not report an analysis plan or completed analyses.

Enrollment was four participants. The outcome description notes that one withdrew before the visit and one could not complete the HP MRI, but does not detail the data status or reason for unusable data for every other enrollee. The adverse-event entry lists three participants at risk, and the registry does not explain how that at-risk group was defined or how it relates to enrollment. Complete follow-up durations and outcome ascertainment procedures are not reported in the registry record.

The single-group, nonrandomized design has no concurrent control arm. Consequently, the study cannot provide a randomized comparison with standard MRI, despite listing utility over standard MRI as a secondary objective. The record does not report whether any nonrandomized comparative data were collected.

The primary outcome description combines an adverse-event count with scan completion and scan quality, while the outcome title focuses on CTCAE v4.0 higher than grade 2. The registry does not clarify how these components were to be analyzed together or separately. The reason for termination, detailed eligibility criteria, sample-size justification, interim analyses, missing-data procedures, and analysis populations are not reported in the registry record. These gaps limit interpretation beyond the narrow safety statement recorded before termination.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Utility of Hyperpolarized 13C-pyruvate Metabolic Magnetic Resonance Imaging — NCT04698564.
• Registry record last updated 2026-07-15; status last verified 2026-07.
• Results first posted 2026-07-15.
• 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

NCT04698564 is a Phase 2, single-group study of hyperpolarized 13C-pyruvate metabolic MRI in men suspected or known to have prostate cancer. The registry lists enrollment of 4, no randomization, no masking, and a terminated status. The study start is listed as 2020-12-01 and primary completion as 2025-12-05.

The primary outcome is titled CTCAE v4.0 Higher Than Grade 2, with a timeframe of within three years post treatment. The description also refers to scan completion and a minimum quality standard measured by signal-to-noise ratio. The registry states that the study terminated prematurely, no usable data were obtained, and no patients had treatment-related adverse events higher than grade 2 until termination. It notes one withdrawal before the visit and one participant unable to complete HP MRI.

The safety entry reports three at risk and zero affected for serious adverse events, three at risk and zero affected for other adverse events, and zero deaths. The registry lists diagnostic accuracy, utility over standard MRI, and tissue-metabolite correlation as secondary outcomes, but reports zero analyses. The diagnostic and imaging-performance questions therefore remain unanswered in the posted results.