1% Chloroprocaine(PF) vs. Bupivacaine Spinals: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 1% Chloroprocaine(PF) vs. Bupivacaine Spinals (NCT03324984), a randomized phase 2 study. The primary outcome is Recovery Time.

2. Clinical Question

The clinical question is whether recovery after spinal anesthesia differs between patients assigned to 1% chloroprocaine and those assigned to 0.75% bupivacaine for hemorrhoidectomy in an ambulatory surgery center. Recovery time is defined as the time until both motor and sensory function have returned. The registry description also identifies voiding time as part of the study’s discharge-time objective, but the primary outcome reported in the results is recovery time.

3. Trial Design

The registry describes a completed phase 2, randomized, parallel-group trial sponsored by Montefiore Medical Center. It lists an enrollment of 110 and dates the study start to 2019-09-11 and primary completion to 2023-02-01. The treatment groups were 1% chloroprocaine and 0.75% bupivacaine, both administered as spinal anesthesia for patients undergoing hemorrhoidectomy.

The masking field identifies the study as triple masked, while the official title calls it double-blind. The registry record does not identify which study roles were masked or explain the difference in terminology. Allocation is recorded as randomized. The record does not report further details about how the random sequence was generated, how assignments were concealed, or whether any participants or staff were unmasked.

The primary outcome is recovery time, measured in minutes as the time until both motor and sensory function had returned. The described assessment schedule was on post-operative day 1, approximately every 15 minutes up to 24 hours. The registry’s study summary also refers to discharge time, defined in that summary in relation to voiding time, but a posted result for that measure is not included in the outcome information. The listed secondary outcomes are evidence of hypotension and evidence of transient neurological symptoms.

The arm-level recovery summaries contain 54 participants for 1% chloroprocaine and 51 for 0.75% bupivacaine. The record does not explain the relationship between these outcome counts and the enrollment figure. Eligibility criteria, exclusions, treatment adherence, withdrawals, and the analysis population are not reported in the registry record. The original protocol and the trial’s own sample-size justification are also 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

Reasons for not completing this period:

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 Recovery Time, measured over On post-operative day 1 (POD1), approximately every 15 minutes up to 24 hours.

Recovery time is a continuous outcome measured in minutes. It is defined as the time from the postoperative assessment period until both motor and sensory function have returned. Motor recovery was assessed by mobility of both lower extremities, including the hips, knees, and lower legs, using the Bromage scale. Sensory recovery was assessed using light touch and/or pinprick in dermatomes corresponding to the T8-S2 spinal cord segments. The time at which both functions were re-established was recorded.

This endpoint is relevant to the study’s recovery question because it combines return of movement and sensation rather than treating either measure alone as complete recovery. The registry describes repeated assessments on post-operative day 1, approximately every 15 minutes up to 24 hours. The arm results are summarized with means and standard errors.

In the posted results, mean recovery time is 134.1 minutes for 1% chloroprocaine and 161.9 minutes for 0.75% bupivacaine. The registry’s stated objective also mentions discharge time, with voiding time identified as the discharge-related measure, but a result for that outcome is not reported in the posted primary-outcome summary. The registry record does not report a threshold for what would count as a clinically important difference in recovery time.

7. Results Posted in the Registry

• 0.75% Bupivacaine: mean 161.90 versus 134.10 on control; difference 27.80 (95% CI 1.50 to 54.10), standardized effect d = 0.41; z-test p = 0.038.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: recovery time is recorded in minutes, and the registry summarizes it with a mean for each arm. A mean gives the arithmetic center of the observed measurements. It is useful for describing average recovery time, but it does not show the full distribution. Two groups can have different means while still having substantial overlap in individual values. The registry record does not provide medians, ranges, or individual-level distributions for this outcome.

What do the arm summaries describe?

The 1% chloroprocaine arm has a reported mean of 134.1 minutes and standard error of 8.6 minutes. The 0.75% bupivacaine arm has a reported mean of 161.9 minutes and standard error of 10.3 minutes. The arm counts are 54 and 51, respectively. The standard error describes the precision of an estimated mean, not the typical distance of an individual participant’s recovery time from that mean. It should not be read as a standard deviation.

In general, the standard error of a mean reflects both the variability in observed values and the number of observations. A smaller standard error generally indicates a more precise estimate of the group mean, but does not imply that individual outcomes are tightly clustered. The registry record does not report the standard deviations of recovery time or enough detail to reconstruct the individual-level distribution.

How should the difference be read?

The posted comparison is a mean difference of 27.8 minutes, stated as the 0.75% bupivacaine mean minus the 1% chloroprocaine mean. Its positive direction corresponds to the larger mean in the bupivacaine group. The confidence interval is 1.501 to 54.1 minutes. A confidence interval gives a range of values compatible with the data and the method’s assumptions; it is not a guarantee that the true value lies within the particular interval. A wider interval indicates less precision than a narrower interval.

The unadjusted p-value is 0.038. In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model, assuming that model and its assumptions hold. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of the difference. The registry record does not report the detailed test used to obtain the p-value or the method used to construct the confidence interval.

What does unadjusted mean?

An unadjusted comparison contrasts the groups without accounting for other measured characteristics through a statistical adjustment model. This can be a clear description of a randomized comparison, but it does not show whether estimates would change after adjustment for baseline factors. No adjusted estimate is reported in the registry record. The record also does not report a detailed statistical analysis plan, including planned covariates, model specifications, or diagnostic checks.

Random assignment is intended to make treatment groups comparable on average, including for characteristics that were not measured. It does not ensure that groups will be identical in a particular trial, especially when the number of participants is limited. Baseline characteristics are not included in the registry record described for this analysis, so the balance of the groups cannot be assessed from the posted primary-outcome summaries.

Why does the assessment schedule matter?

The outcome description says assessments occurred on post-operative day 1, approximately every 15 minutes up to 24 hours. Repeated assessment can locate recovery within the interval between checks rather than at a continuously observed instant. The registry record does not explain how times between assessments were handled, how the assessment schedule was applied if a participant was unavailable, or how any recovery time not observed within the stated period was treated.

Recovery time is a time-to-event type of measure in the ordinary statistical sense: the event is return of both motor and sensory function. However, the posted results summarize it as an arm mean, and the registry record does not report a time-to-event analysis, censoring rules, or a distributional model. It would therefore be inappropriate to infer that a particular time-to-event method was used.

The registry identifies four outcome measures and names evidence of hypotension and evidence of transient neurological symptoms as secondary outcomes. It reports no separate analysis entries. The record does not provide enough detail to determine how the multiple outcomes were incorporated into formal inference, or whether any adjustment for multiple testing was planned. These reporting gaps matter when interpreting the p-value as one result among several outcomes.

10. Confidence Intervals and Precision

The confidence interval for the reported mean difference extends from 1.501 to 54.1 minutes, with the comparison defined as the bupivacaine mean minus the chloroprocaine mean. The interval expresses uncertainty about the size of the difference. Its lower end is close to zero relative to its upper end, so the posted estimate is more precise about the direction than about the magnitude. The interval remains broad enough to include a range of possible positive differences.

In general, a confidence interval is constructed by a statistical procedure that, under repeated use and its assumptions, has a specified coverage property. It is not a probability statement about the fixed true difference after the data have been observed. Interpretation also depends on the method used to calculate it. The registry record does not report that method, so the interval should be read as the interval posted with the results rather than reconstructed under an assumed model.

The arm-specific standard errors are 8.6 minutes and 10.3 minutes. They indicate uncertainty in the estimated group means, not the variation among individual participants. The registry record does not give standard deviations or individual observations, which limits assessment of the outcome’s distribution and the influence of unusually long or short recovery times.

Precision is also shaped by the outcome counts. The summaries report 54 participants in the chloroprocaine group and 51 in the bupivacaine group. The enrollment figure is 110, and the reasons these numbers differ are not reported in the registry record. Without details about exclusions, missing outcomes, and the analysis population, it is not possible to determine how the analyzed participants relate to all enrolled participants.

The interval addresses statistical uncertainty in the reported mean difference; it does not establish clinical importance or resolve limitations in reporting. The registry record does not state a threshold for a meaningful recovery-time difference. It also does not report adjusted estimates or a detailed analysis plan. Those issues are distinct from the width of the confidence interval and should be considered separately.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations for this continuous recovery-time outcome. They are participants per arm, not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The registry record does not report the trial’s original sample-size assumptions or justification.

The rows consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For each assumed effect, the 80% power column gives the participants per arm associated with an 80% chance of detecting an effect of that size under the planning assumptions, if the assumed effect is the true effect and the model is appropriate. The 90% power column expresses the same kind of planning target with a higher chance of detection. These are design probabilities, not probabilities that a particular result is true.

The posted figures increase as the assumed effect becomes smaller. That pattern is expected: a smaller difference is harder to distinguish from sampling variation, so more participants are generally needed to detect it with the same target power and significance level. For example, the planning row for 75% of the observed effect gives 170 participants per arm for 80% power and 227 participants per arm for 90% power. The row for 50% of the observed effect gives 381 participants per arm for 80% power and 510 participants per arm for 90% power.

These figures are not observed power. They are hypothetical planning values based on the observed effect and the stated assumptions, not a retrospective measure of the probability that this completed trial detected an effect.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 27.800; pooled standard deviation σ = 68.422.
2. n = 2 × (1.96 + 0.842)² × 68.422² / 27.800² = 95.1, rounded up to 96 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 27.8                      # observed difference in means
sigma <- 68.4220923273076                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3324984)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 96 (80% power), 128 (90% power)
 75% of observed effect: n per arm = 170 (80% power), 227 (90% power)
 50% of observed effect: n per arm = 381 (80% power), 510 (90% power)
power.t.test: 96.1 
Simulated power at n = 96 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and names two secondary outcomes: evidence of hypotension and evidence of transient neurological symptoms. Recovery time is identified as the primary outcome. The record’s study summary also refers to voiding time in relation to discharge. Results for those other measures are not included in the primary recovery-time figures, and the registry record does not report their numerical results in the information used for this analysis.

When a study examines more than one outcome or makes multiple comparisons, the chance of observing at least one apparently unusual result can increase. Statistical methods may address this multiplicity, for example by defining a primary outcome in advance or adjusting inference across several tests. The registry record does not report whether a multiplicity strategy was prespecified or applied. The unadjusted p-value should therefore be understood as a result for the reported comparison, not as evidence that multiplicity has been addressed.

The registry record lists no separate analysis entries. It does not report an analysis population, whether participants were analyzed according to randomized assignment, how protocol deviations were handled, or whether any per-protocol or other populations were used. These details are important for understanding which participants contribute to the estimate and how the analysis relates to randomization.

Missing-data handling is not reported in the registry record. The primary-outcome arm counts are 54 and 51, whereas enrollment is listed as 110; reasons for the difference are not reported. The record does not state how many participants lacked recovery-time measurements, whether missingness differed by arm, or whether any imputation or sensitivity analysis was conducted. Without that information, the possible influence of missing outcomes cannot be assessed from the posted summary alone.

The original statistical analysis plan, including planned handling of multiple outcomes, missing data, and analysis populations, is not reported in the registry record. These omissions do not establish that no such methods were used; they mean that the methods cannot be verified from the registry record.

14. 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 serious adverse-event figures list 54 participants at risk in the 1% chloroprocaine arm and 51 in the 0.75% bupivacaine arm. The reported number affected by serious adverse events is 0 in each arm. The figures for other adverse events are also 0 in each arm, and deaths are reported as 0 in both groups. No serious-event terms are listed.

These are counts in the registry’s adverse-event summary. A zero count means that no events of that category were reported for the listed participants in the posted results; it does not prove that an event is impossible or that the treatments have no risks. The registry record does not provide event definitions, ascertainment procedures, severity details beyond the serious-versus-other distinction, or the observation period for these counts. It also does not report a separate safety analysis.

The safety figures should be considered alongside the recovery-time findings, not as a measure of the precision of that outcome. The primary outcome counts and adverse-event risk counts are consistent within each arm in the posted summaries, but the record does not explain how these counts relate to the total enrollment figure.

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

The posted results describe shorter average recovery time in the 1% chloroprocaine arm than in the 0.75% bupivacaine arm. The group means are 134.1 and 161.9 minutes, respectively, and the reported mean difference is 27.8 minutes when expressed as bupivacaine minus chloroprocaine. The confidence interval, 1.501 to 54.1 minutes, conveys uncertainty in the estimated difference. The unadjusted p-value is 0.038.

These results do not by themselves establish whether the difference is important to patients, clinicians, or discharge processes. The registry record does not report a threshold for clinical importance, nor does the primary-outcome summary provide a result for voiding time or discharge time. The record’s description of the study objective and its posted recovery-time result should therefore be distinguished: the results presented for recovery time do not answer every part of the stated objective.

The findings also do not establish that the observed difference would be the same in other settings or populations. The record describes a pilot trial in an ambulatory surgery center, but detailed eligibility criteria and baseline participant characteristics are not reported in the registry record for this analysis. Generalizability cannot be assessed fully from the arm means alone.

The serious and other adverse-event counts are zero in both groups in the posted summary. Those counts describe what was reported for the listed participants and do not demonstrate absence of risk. The registry record does not report the adverse-event observation period or detailed ascertainment methods.

Finally, the registry record does not include the original sample-size justification, detailed statistical analysis plan, missing-data methods, or analysis population. These gaps limit assessment of whether the posted analyses followed prespecified methods and how incomplete outcome data may have affected the estimate. The appropriate reading is a comparison of the reported group summaries with uncertainty, rather than a definitive answer about clinical benefit, safety, or outcomes beyond recovery time.

16. Why This Trial Matters Statistically

This trial illustrates how a continuous recovery outcome can be summarized and compared between randomized groups. Reporting both arm means and a mean difference makes the direction of the contrast interpretable: the posted estimate is calculated as the bupivacaine mean minus the chloroprocaine mean. Pairing that estimate with a confidence interval helps readers see that the data do not determine the difference precisely.

It also illustrates why standard errors should not be mistaken for the spread of participants’ outcomes. The standard errors describe uncertainty in estimated means, while individual recovery times may vary more widely. Without standard deviations, distributions, or individual observations, the degree of participant-level variability cannot be judged from the mean summaries alone.

The registry record identifies a pilot trial and reports an enrollment figure alongside smaller arm-level outcome counts. That makes clear the importance of distinguishing enrollment from the number contributing to a particular outcome analysis. Because the reasons for the difference are not reported, the impact of exclusions or missing outcome data cannot be evaluated from the posted results.

The record also names additional outcomes related to discharge and safety, while the primary numerical result concerns recovery time. A prespecified hierarchy of outcomes and clear reporting of all measured outcomes are important for placing a single p-value in context. The record does not report whether multiplicity was addressed or how the original statistical plan treated the various outcomes.

Finally, the planning illustrations demonstrate how sample-size requirements depend on the effect size to be detected and the target power. Such illustrations help explain design tradeoffs, but they are not a substitute for the trial’s original sample-size rationale, which is not reported in the registry record. Taken together, the trial is useful for understanding estimation, precision, reporting, and planning without treating a pilot result as a complete account of all clinical questions.

17. 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 primary-outcome summary is limited to group means, standard errors, a mean difference, a confidence interval, and an unadjusted p-value. The registry record does not report the standard deviations or individual recovery times, so the distribution, outliers, and potential skew in recovery time cannot be assessed. The exact statistical procedures used for the interval and p-value are also not reported.

The outcome counts are 54 for 1% chloroprocaine and 51 for 0.75% bupivacaine, while the enrollment figure is 110. Reasons for this difference, including any exclusions or unavailable measurements, are not reported. Missing-data methods and the analysis population are not reported, limiting assessment of whether the group summaries include all randomized participants or another subset.

The registry record does not report baseline characteristics, eligibility details, treatment adherence, protocol deviations, or methods of allocation concealment. It identifies triple masking, whereas the official title uses double-blind terminology; the roles masked and the reason for the difference are not reported. These gaps make it difficult to assess trial conduct and the comparability of the analyzed groups.

Only the recovery-time comparison is described numerically in the primary-outcome information. The stated discharge-related objective and named secondary outcomes do not have numerical results in this summary. The record does not report a multiplicity plan, a detailed statistical analysis plan, or the trial’s own sample-size justification. It also does not report a clinically important difference threshold. These limitations restrict interpretation of the result’s clinical importance and of how completely the posted analysis reflects the trial’s planned questions.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: 1% Chloroprocaine(PF) vs. Bupivacaine Spinals — NCT03324984.
• Registry record last updated 2025-02-28; status last verified 2025-02.
• Results first posted 2025-02-28.
• 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.

21. Record Summary

The registry record describes a completed phase 2 randomized parallel-group trial sponsored by Montefiore Medical Center. It compares spinal 1% chloroprocaine with 0.75% bupivacaine in patients undergoing hemorrhoidectomy in an ambulatory surgery center. The record lists enrollment of 110 and study dates from 2019-09-11 to primary completion on 2023-02-01.

The primary outcome is recovery time in minutes, defined as return of both motor and sensory function. Mean recovery times are 134.1 minutes for chloroprocaine and 161.9 minutes for bupivacaine. The reported mean difference is 27.8 minutes, with a confidence interval from 1.501 to 54.1 minutes and an unadjusted p-value of 0.038.

Secondary outcomes named in the record are hypotension and transient neurological symptoms. The adverse-event summary reports zero serious events, zero other adverse events, and zero deaths in both groups. Further detail about the analysis plan, missing data, analysis population, sample-size rationale, and results for other outcomes is not reported in the registry record.