Lactated Ringers With or Without Rectal Indomethacin to Prevent Post-ERCP Pancreatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lactated Ringers With or Without Rectal Indomethacin to Prevent Post-ERCP Pancreatitis (NCT02641561), a randomized phase 3 study. The primary outcome is The Number of Participants With Acute Pancreatitis After ERCP as Assessed by Worsening Abdominal Pain Plus Either Elevated Amylase or Lipase 3 x Upper Limit of Normal.

2. Clinical Question

The central statistical question is about the observed frequency of an event in randomized treatment groups, rather than a comparison of average laboratory values or time until an event. The registry's stated aim was to evaluate the combination of the two strategies against either strategy alone. The posted primary comparisons use normal saline plus placebo as the reference for each active-strategy arm. That structure permits interpretation of each reported comparison against the reference group, but does not by itself provide a direct statistical comparison between the indomethacin-only and lactated-Ringer's-only arms, or between either single strategy and the combination.

3. Trial Design

This is a randomized, phase 3, parallel-group trial with quadruple masking in the registry record. The registry lists an enrollment of 192 and a completed status. The recorded study start is 2014-10, and primary completion is recorded as 2016-06. The sponsor is Cooper Norcross Health. The primary outcome timeframe is 30 days after ERCP.

The treatment assignments combine fluid and suppository strategies. The reference arm received normal saline intravenously during the procedure and a placebo suppository before the procedure. Another arm paired normal saline with rectal indomethacin. A third paired lactated Ringer's solution, given as 1 Liter intravenously before the procedure, with placebo. The remaining arm paired lactated Ringer's solution with rectal indomethacin. The registry describes the active suppository as 100mg and says it was given prior to the procedure.

Randomization is intended, as a general design principle, to make treatment groups comparable on average with respect to factors that could affect outcomes. Masking is intended to reduce the influence of treatment knowledge on care, outcome assessment, or reporting. The registry labels masking as quadruple, but does not report the identities of the masked parties or the practical masking procedures. The method used to generate the random sequence, allocation concealment details, and any stratification factors are not reported in the registry record.

The posted primary arm results give the number of participants with the endpoint and the group size for each arm. The record does not report a detailed account of participant flow, treatment adherence, withdrawals, or the analysis population. Those details would help determine how closely the analyzed groups followed the original random assignments and how missing outcomes were handled.

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 The Number of Participants With Acute Pancreatitis After ERCP as Assessed by Worsening Abdominal Pain Plus Either Elevated Amylase or Lipase 3 x Upper Limit of Normal, measured over 30 days after ERCP.

The primary endpoint counts participants with acute pancreatitis after ERCP, assessed by worsening abdominal pain plus either elevated amylase or lipase at 3 x the upper limit of normal. The registry specifies a timeframe of 30 days after ERCP. In practical terms, the outcome combines symptoms with a laboratory criterion; an enzyme elevation alone is not the entire stated definition.

Counting participants who meet a specified event definition is useful when the clinical question concerns whether an adverse event occurred during a defined follow-up period. It gives an event count for each treatment group and allows comparisons of the observed frequency between groups. The registry reports this outcome as a count of participants, not as a continuous measure of pain, enzyme level, or illness severity. It does not report separate results for the symptom and laboratory components, nor a severity scale for pancreatitis, in the posted primary outcome results.

As a general statistical point, a clear endpoint definition and timeframe help make a comparison interpretable: they specify what qualifies as an event and the period in which it is counted. The registry's definition therefore provides a rule for classifying events, while the arm counts describe how often that rule was met in the posted results. Whether all outcomes were assessed consistently and whether any cases were missed are not reported in the registry record.

7. Results Posted in the Registry

• B (NS+IND): 12.5% (6/48) versus 20.8% (10/48) on control; risk difference -8.3 percentage points (95% CI -23.1 to 6.5), risk ratio 0.60 (0.24–1.52); unadjusted two-proportion z-test p = 0.273.
• C (LR+Placebo): 18.8% (9/48) versus 20.8% (10/48) on control; risk difference -2.1 percentage points (95% CI -18.0 to 13.9), risk ratio 0.90 (0.40–2.02); unadjusted two-proportion z-test p = 0.798.
• D (LR+IND): 6.2% (3/48) versus 20.8% (10/48) on control; risk difference -14.6 percentage points (95% CI -28.0 to -1.2), risk ratio 0.30 (0.09–1.02); unadjusted two-proportion z-test p = 0.037.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

The Number of Participants With Acute Respiratory Distress Syndrome (ARDS) After ERCP as Assessed by ARDSnet Criterion (Below)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • B (NS+IND): 0.0% (0/48) versus 2.1% (1/48) on control; risk difference -2.1 percentage points (95% CI -6.1 to 2.0); unadjusted two-proportion z-test p = 0.315.
  • C (LR+Placebo): 0.0% (0/48) versus 2.1% (1/48) on control; risk difference -2.1 percentage points (95% CI -6.1 to 2.0); unadjusted two-proportion z-test p = 0.315.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B (NS+IND) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C (LR+Placebo) and the control. The interval gives the range of effects that remain compatible with the data.

The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • B (NS+IND): 12.5% (6/48) versus 20.8% (10/48) on control; risk difference -8.3 percentage points (95% CI -23.1 to 6.5), risk ratio 0.60 (0.24–1.52); unadjusted two-proportion z-test p = 0.273.
  • C (LR+Placebo): 18.8% (9/48) versus 20.8% (10/48) on control; risk difference -2.1 percentage points (95% CI -18.0 to 13.9), risk ratio 0.90 (0.40–2.02); unadjusted two-proportion z-test p = 0.798.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B (NS+IND) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C (LR+Placebo) and the control. The interval gives the range of effects that remain compatible with the data.

The Number of Participants With Multiple Organ Failure (MOF) After ERCP as Assessed by Elevated Creatinine Blood Test

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • B (NS+IND): 2.1% (1/48) versus 0.0% (0/48) on control; risk difference 2.1 percentage points (95% CI -2.0 to 6.1); unadjusted two-proportion z-test p = 0.315.
  • C (LR+Placebo): 0.0% (0/48) versus 0.0% (0/48) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B (NS+IND) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C (LR+Placebo) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover other complications or clinical conditions after ERCP, including acute respiratory distress syndrome, systemic inflammatory response syndrome, multiple organ failure, and sepsis. The posted secondary results include sparse events for some outcomes and no events in some arm-outcome combinations. Across the available results, there is no uniformly informative pattern across all outcomes: event occurrence is limited, and the reported estimates do not consistently establish differences from the reference.

These outcomes relate to the primary result because they describe additional events that may occur after ERCP and may be relevant to the clinical course. They are not substitutes for the primary endpoint, which has its own stated definition based on worsening abdominal pain and enzyme elevation. A pattern in a secondary outcome cannot confirm or refute the primary result, particularly when the events are uncommon and the registry record does not provide a comprehensive analysis of relationships among outcomes.

The displayed secondary findings should be interpreted cautiously because the p-values are unadjusted and the registry lists multiple outcome measures. As a general statistical principle, testing many outcomes can increase the chance that some results appear unusual even when there is no underlying difference. Whether the investigators prespecified a hierarchy, selected a limited family of confirmatory outcomes, or adjusted for multiplicity is not reported in the registry record. Unadjusted secondary results therefore carry less weight as evidence of a treatment difference than a result from a clearly prespecified and appropriately analyzed primary comparison.

The registry record does not contain posted results for every listed secondary outcome in the registry record of the study record, and additional outcome definitions or analysis details are not reported in the registry record. The available secondary information is best treated as descriptive and hypothesis-generating. It does not support broad claims about the full range of post-ERCP complications.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• The Number of Participants With Acute Respiratory Distress Syndrome (ARDS) After ERCP as Assessed by ARDSnet Criterion (Below)
• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
• The Number of Participants With Sepsis After ERCP as Assessed by Infectious Source Defined by Positive Microbiology Culture

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference describe?

The primary comparisons are expressed as risk differences. In general, a risk difference is the event frequency in one group minus the event frequency in a reference group. A value below no difference indicates fewer observed events in the comparison group; a value above no difference indicates more. The posted estimates are unadjusted comparisons of the arm-level results. They do not account for additional participant characteristics in a regression model, and the registry record does not describe adjusted primary analyses.

The interpretation is anchored to the named reference arm: normal saline plus placebo. The comparison for each other arm is not an overall comparison of all active strategies combined. It also does not directly test whether one active strategy differs from another. General statistical guidance is to keep the contrast in view whenever interpreting an estimate: a risk difference answers a question about an absolute difference in event frequency for the particular two groups being compared.

How should a confidence interval be read?

In general, a confidence interval describes the uncertainty around an estimate under the assumptions of the method used to construct it. Its endpoints mark a range of values compatible with the data and method; the interval is not a guarantee that the true effect lies inside it. If a risk-difference interval includes no difference, the results are compatible with no difference as well as with differences in either direction represented by the interval. If the interval lies on one side of no difference, that is a different interval-based signal, but it does not eliminate concerns about precision, analysis choices, or multiplicity.

The registry reports intervals for its risk-difference comparisons and also reports risk-ratio and odds-ratio intervals for the primary endpoint. These are different effect measures. A risk ratio compares event frequencies as a ratio, while an odds ratio compares event odds. Their null values are not the same as the null value for a risk difference: a ratio has no difference represented by a value of one, while a difference has no difference represented by zero. The results are based on the same arm data, but the estimates and interval calculations can look different because the measures and their scales differ.

What does an unadjusted p-value say?

As a general explanation, a p-value measures how unusual data at least as discordant with a specified null hypothesis would be if that null hypothesis and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, nor the probability that the observed result occurred by chance. The registry labels the posted p-values as unadjusted. They should be read as results for individual comparisons without assuming that correction for multiple testing was applied.

The primary comparison p-values are 0.273 for normal saline plus indomethacin, 0.798 for lactated Ringer's plus placebo, and 0.037 for lactated Ringer's plus indomethacin, each versus the normal-saline-plus-placebo reference. These values should be considered alongside the estimates, confidence intervals, and study context rather than treated as a complete measure of evidence. The registry record does not report the statistical test used to obtain the p-values, the interval construction method, or whether a prespecified decision threshold governed the primary analysis.

Why are sparse event data important?

There were relatively few primary events in the posted arm counts. As a general statistical point, limited event information often produces imprecise estimates: a small change in the number of observed events can have a noticeable effect on an estimated group difference. This is one reason confidence intervals are useful. They show that the point estimate alone does not convey how uncertain a comparison is.

Rare events can also create practical difficulties for ratio measures and their intervals. A ratio may be unstable when event counts are small, and an arm with no events can make a conventional ratio calculation especially sensitive to the chosen method. The secondary ARDS results include groups with no events, but the registry record does not report the calculation methods for those comparisons. No additional modeling method should be inferred from the posted numbers.

What information is absent from the analysis record?

The registry record does not report the primary statistical analysis plan, the exact test or model, covariate adjustment, a missing-data approach, or the population used for analysis. It does not report whether the analysis followed intention-to-treat principles or how protocol deviations were handled. The randomization and masking labels describe design features, not the details of the analysis. These omissions limit assessment of whether the posted estimates were produced according to a prespecified plan and how robust they are to alternative reasonable methods.

The study description lists 20 outcome measures and the record lists multiple secondary outcomes. General statistical reasoning says that examining multiple outcomes and contrasts raises the chance of at least one apparently unusual result, unless the analysis plan accounts for that multiplicity. Whether such an adjustment or a hierarchy among endpoints was planned is not reported in the registry record. The primary endpoint result should therefore be distinguished from exploratory or unadjusted secondary findings.

11. Confidence Intervals and Precision

Precision is about how narrowly the data locate an effect estimate. The posted primary risk-difference intervals for the normal-saline-plus-indomethacin and lactated-Ringer's-plus-placebo comparisons include no difference and extend in both directions. That means these data do not pin down whether either comparison has fewer events, more events, or little difference relative to the reference. Their p-values are also not small, but the intervals are the more direct description of the range of effects compatible with the analysis.

The risk-difference interval for lactated Ringer's plus indomethacin versus the reference is entirely on the side corresponding to fewer events. However, the estimates remain based on a limited number of observed events, and the ratio-measure intervals give a different picture of precision: the risk-ratio interval includes its null value, while the odds-ratio interval is below its null value. The registry does not report how those intervals were constructed. This makes it important not to treat a single interval or p-value as the entire interpretation.

In general, confidence intervals are affected by the amount of information in the data, including the group sizes and number of events. They do not capture every source of uncertainty, such as possible outcome misclassification, departures from the analysis plan, or bias from missing data. The registry record does not report enough detail to assess those sources. The intervals quantify uncertainty under the methods used, whose full details are not reported in the registry record.

The observed point estimates summarize the sample results, not a guaranteed effect in a future study or another population. A narrow estimate would indicate greater statistical precision under the analysis assumptions; broad intervals indicate that multiple effects remain compatible with the observed data. Here, the posted comparisons should be interpreted with attention to both the interval locations and their breadth, and not solely by whether a p-value is above or below a conventional threshold.

12. 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 derived from the observed effect, not the original trial's design calculations. They are stated as participants per arm for 80% power and participants per arm for 90% power. They are not total sample sizes and do not refer to total events. The sample-size assumptions in the registry-derived calculation are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect.

In plain terms, the 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under those planning assumptions. The 90% power column uses a higher target chance of detection and therefore generally requires more participants per arm. These are design illustrations, not a measure of how much power the completed trial actually had; this is not observed power.

Each comparison has its own planning figures because the observed differences vary. For lactated Ringer's plus indomethacin versus the reference, planning for 100% of the observed effect gives 86 participants per arm for 80% power and 114 participants per arm for 90% power. Planning for 75% of the observed effect gives 170 participants per arm for 80% power and 227 participants per arm for 90% power; planning for 50% gives 420 participants per arm for 80% power and 561 participants per arm for 90% power. Smaller effects require more participants to detect under the same assumptions.

The figures depend strongly on the observed effect used as the planning basis. An observed effect from a relatively small study can be an unstable estimate, so these calculations should not be treated as a guarantee that a future study will achieve the stated power. The original protocol's sample-size justification and design assumptions are not reported in the registry record. The curve is a visual expression of the same planning relationship; it should be read as an illustration rather than as evidence about the completed trial's power.

13. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.208; treatment proportion p₁ = 0.125; average p̄ = 0.167.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5270 = 1.0330.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5237 = 0.4408.
4. n = (1.0330 + 0.4408)² / (-0.0833)² = 312.8, rounded up to 313 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
p0 <- 0.208333333333333                          # control proportion
p1 <- 0.125                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2641561)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 313 (80% power), 419 (90% power)
 75% of observed effect: n per arm = 585 (80% power), 782 (90% power)
 50% of observed effect: n per arm = 1,377 (80% power), 1,842 (90% power)
power.prop.test: 312.8 
Simulated power at n = 313 per arm: 0.809 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures and more than one treatment comparison. The primary outcome is acute pancreatitis, while secondary outcomes include additional complications and clinical events. When several outcomes or comparisons are examined, the probability of observing at least one result that looks unusual can increase. General statistical methods address this issue by prespecifying a primary contrast, using a testing hierarchy, or adjusting for multiple comparisons. Whether any such approach was planned or used is not reported in the registry record.

The posted comparison p-values are described as unadjusted. They should not be read as if a multiplicity correction had been applied. The record does not say whether the primary comparison was the sole confirmatory test, whether the other arm comparisons were exploratory, or how the family of tests was defined. The multiplicity issue is especially relevant to interpreting an isolated p-value in the context of several outcomes and contrasts.

Missing-data procedures are also not reported in the registry record. The posted arm results provide group sizes and event counts, but do not describe whether every randomized participant had complete endpoint follow-up, how missing outcome status was classified, or whether any imputation or sensitivity analysis was used. The flow of participants after randomization, reasons for withdrawal, and handling of protocol deviations are not reported in the registry record.

The analysis population is not reported in the registry record. The randomization label does not establish that the posted analyses followed an intention-to-treat approach, nor does it show whether a per-protocol or other population was used. The statistical analysis plan, covariate adjustment, and exact methods for constructing intervals and p-values are also not reported in the registry record. These gaps make it difficult to judge whether analysis choices were prespecified or to reproduce the reported comparisons independently. They do not invalidate the arm counts, but they limit how fully the inferential results can be evaluated.

15. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events in any of the arms. It also reports other adverse events and deaths separately. Other adverse events were reported for 2 participants in the normal-saline-plus-placebo arm and 1 participant in each of the other arms. Deaths were reported for 1 participant in the normal-saline-plus-placebo arm, 2 in the normal-saline-plus-indomethacin arm, 2 in the lactated-Ringer's-plus-placebo arm, and 1 in the lactated-Ringer's-plus-indomethacin arm.

These are descriptive counts. The registry record does not provide event descriptions for the other adverse events, an assessment of whether events were considered related to study treatment, or a narrative explaining the deaths. The record lists no serious adverse event terms. The counts should not be interpreted as evidence that any particular regimen caused or prevented an adverse event, and the small numbers do not support a precise comparison of safety between arms. The meaning of the adverse-event observation period and the methods used to collect and classify events are not reported in the registry record.

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

The primary result describes the number of participants meeting a specified acute-pancreatitis definition within 30 days after ERCP. The posted count was highest in the normal-saline-plus-placebo reference arm and lowest in the lactated-Ringer's-plus-indomethacin arm. The corresponding comparison with the reference has an unadjusted p-value of 0.037 and a risk-difference interval on the side of fewer events. This is evidence of a difference in the posted comparison under its analysis, but it is not by itself a definitive account of the effect or its reliability.

The comparisons for normal saline plus indomethacin and lactated Ringer's plus placebo have intervals that include no difference. Their posted results do not distinguish a reduction from no difference or an increase with precision. The results therefore do not establish a clear difference for those individual comparisons. Nor do the reference-arm comparisons establish whether the combined strategy is better than either single strategy, because direct comparisons between active arms are not reported.

The result does not establish causation beyond the limits of the trial design and analysis information available in the registry. Although randomization is recorded, details of the analysis population, missing outcomes, statistical methods, and multiplicity handling are not reported in the registry record. These omissions leave uncertainty about how the estimates were obtained and how broadly they should be interpreted. The result also concerns the registry-defined endpoint and timeframe, not every possible measure of pancreatitis, illness severity, or longer-term outcome.

Statistical evidence should not be reduced to a binary statement about whether a p-value passes a threshold. The estimated difference, its confidence interval, the small number of observed events, the multiple comparisons, and the missing analysis details all matter. The posted results support a careful description of the event counts and comparisons, not medical advice or a claim that a regimen works or does not work.

17. Why This Trial Matters Statistically

This trial is statistically informative because it compares fluid and medication strategies in a randomized design and reports arm-level event counts for a defined post-ERCP outcome. The design separates a reference regimen from strategies that add indomethacin, substitute lactated Ringer's solution, or combine both. That makes the clinical question more specific than a simple comparison of one treatment with no treatment, while also creating several possible contrasts that require clear interpretation.

The results illustrate why a point estimate, a confidence interval, and a p-value should be read together. The combined-strategy comparison has a risk-difference interval on one side of no difference, but ratio-measure intervals do not all present the same interval-based signal. The other comparisons have uncertainty spanning no difference. This emphasizes that effect measures answer related but distinct questions, and that sparse event counts can limit precision even when an estimated contrast appears notable.

The record also illustrates the difference between a completed randomized trial and a fully documented statistical analysis. The design labels and posted results are useful, but the absence of details about the analysis plan, missing data, participant flow, and multiplicity makes it difficult to assess how confirmatory the reported comparisons were. These issues are central to interpreting clinical trial results, not administrative details.

Finally, planning calculations based on observed effects should not be mistaken for the completed trial's observed power or for the original design rationale. They show how sample-size needs change under stated hypothetical assumptions. The original sample-size justification is not reported in the registry record. Together, these considerations make the trial a useful example of interpreting a randomized comparison while keeping uncertainty and reporting limitations visible.

18. 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.

Several limitations specific to this record affect interpretation. The primary outcome counts participants meeting a composite symptom-and-laboratory definition, but the registry does not report the component results separately or provide a severity breakdown. It is therefore not possible to determine from the posted primary endpoint counts whether group patterns differed for pain, enzyme elevation, or more severe pancreatitis classifications.

The event counts are limited, and the comparisons have varying degrees of precision. In particular, the posted confidence intervals do not all give the same impression across risk difference, risk ratio, and odds ratio for the combined strategy comparison. The registry does not report the methods used to construct the intervals or explain that difference. This constrains a detailed appraisal of the statistical calculations.

The primary reported comparisons use the normal-saline-plus-placebo arm as reference. Direct statistical comparisons between the active arms are not reported. Consequently, the results cannot establish a ranking among indomethacin alone, lactated Ringer's alone, and their combination. The registry also does not report details of random sequence generation, allocation concealment, masking procedures, participant flow, or treatment adherence.

Important analysis details are absent: the original statistical analysis plan, analysis population, missing-data handling, covariate adjustment, and multiplicity strategy are not reported in the registry record. In addition, the listed secondary outcomes are numerous, while the available posted secondary results are limited. These limitations do not change the recorded event counts, but they restrict assessment of selection, precision, robustness, and the role of secondary findings.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Lactated Ringers With or Without Rectal Indomethacin to Prevent Post-ERCP Pancreatitis — NCT02641561.
• Registry record last updated 2018-02-27; status last verified 2018-01.
• Results first posted 2018-02-27.
• 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.

22. Record Summary

NCT02641561 is a completed randomized phase 3 parallel-group trial with quadruple masking, sponsored by Cooper Norcross Health. It enrolled 192 participants, with study start recorded as 2014-10 and primary completion as 2016-06. The trial compared normal saline plus placebo with regimens involving rectal indomethacin, lactated Ringer's solution, or both.

The primary endpoint was the number of participants with acute pancreatitis after ERCP, defined by worsening abdominal pain plus either elevated amylase or lipase at 3 x the upper limit of normal, assessed through 30 days after ERCP. The posted arm counts were 10 of 48 for the reference, 6 of 48 for normal saline plus indomethacin, 9 of 48 for lactated Ringer's plus placebo, and 3 of 48 for lactated Ringer's plus indomethacin. The combined-strategy comparison had an unadjusted p-value of 0.037; interpretation remains limited by sparse events and analysis details not reported in the registry record.

The record reports no serious adverse events and lists other adverse events and deaths by arm. The original sample-size justification, analysis population, missing-data methods, and multiplicity approach are not reported in the registry record.