Acute Headache Treatment in Pregnancy: Occipital Nerve Block vs PO Acetaminophen With Caffeine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acute Headache Treatment in Pregnancy: Occipital Nerve Block vs PO Acetaminophen With Caffeine (NCT03951649), a randomized phase 4 study. The primary outcome is Number of Participants With Response to Occipital Nerve Block in Pregnancy.

2. Clinical Question

The comparison is about the proportion meeting a stated response definition, not the size of each participant’s change in pain score. Response meant resolution of headache or improvement to mild range, defined as a visual rating score of 3 or lower. The primary outcome timeframe is listed as 60-300 min, while its description identifies assessment at 2 hours. The registry record does not explain the relationship between these timeframe statements.

The trial was randomized and used a parallel-group design. It was open label, so participants and treating providers were not masked to the assigned treatment. The result therefore addresses the recorded outcomes in these two groups, while the lack of masking is relevant when interpreting a subjective symptom response. The registry record does not report further details about the enrolled population, such as eligibility criteria or baseline headache characteristics.

3. Trial Design

This was a randomized, open-label, parallel-group Phase 4 trial sponsored by the University of Alabama at Birmingham. The registry record lists enrollment of 62 participants and a completed status. It describes the study as evaluating response to bupivacaine occipital nerve block compared with an oral Tylenol/caffeine treatment in pregnant patients seeking headache care. The groups had 31 participants each in the posted primary outcome results.

One group received occipital nerve block. The record describes trained OB/GYN providers using palpation of bony landmarks to identify the injection location, cleaning the site, and injecting bupivacaine on both sides. The intervention description is incomplete in the registry record. The comparator group received acetaminophen 650mg by mouth and caffeine 100mg by mouth. No masking was used.

The primary outcome was the number of participants with a response to occipital nerve block in pregnancy. Its definition compares response after the block with response after the oral combination, counting headache resolution or improvement to mild range at 2 hours. The stated primary timeframe is 60-300 min. The registry record also lists 14 outcome measures and 13 analyses, including secondary outcomes covering treatment response, further treatment, consultation, admission, and representation for headache care.

The registry record does not report the randomization sequence method, allocation concealment, detailed eligibility criteria, original sample-size justification, interim analyses, or a full statistical analysis plan. It also does not state whether the primary analysis followed an intention-to-treat or another analysis-population definition. These details should not be inferred from the randomized design or from the posted counts.

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 Response to Occipital Nerve Block in Pregnancy, measured over 60-300 min.

The primary endpoint counts participants whose headache had resolved or improved to mild range after treatment. In the registry definition, mild range corresponds to a visual rating score of 3 or lower. This binary outcome reduces each participant’s symptom assessment to whether the response criterion was met, rather than measuring the full distribution of pain scores or the amount of change for each person.

A response threshold can be useful because it expresses the result in terms of a clinically interpretable state: whether participants reached the specified level of relief by the assessment time. It also allows the proportion meeting the threshold to be compared across randomized groups. That simplification has a cost. People with quite different starting pain levels or degrees of improvement can be counted alike if they meet the same threshold, and changes that do not cross the threshold are not distinguished from no change.

The record specifies the primary assessment at 2 hours in the outcome description, while the outcome timeframe is listed as 60-300 min. The registry record does not explain whether the broader timeframe reflects additional assessments, a window for assessment, or another convention. The posted primary results give participant counts rather than individual pain-score trajectories. They therefore support interpretation of the stated response outcome, not conclusions about every dimension of pain change or later headache course.

7. Results Posted in the Registry

• Oral Acetaminophen/Caffeine Group: 51.6% (16/31) versus 64.5% (20/31) on control; risk difference -12.9 percentage points (95% CI -37.3 to 11.5), risk ratio 0.80 (0.52–1.23); unadjusted two-proportion z-test p = 0.303.

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.

Number of Participants With Need for Crossover Treatment

• 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:
  • Oral Acetaminophen/Caffeine Group: 45.2% (14/31) versus 29.0% (9/31) on control; risk difference 16.1 percentage points (95% CI -7.6 to 39.8), risk ratio 1.56 (0.79–3.05); unadjusted two-proportion z-test p = 0.189.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Oral Acetaminophen/Caffeine Group and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Need for Second Line Treatment

• 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:
  • Oral Acetaminophen/Caffeine Group: 16.1% (5/31) versus 16.1% (5/31) on control; risk difference 0.0 percentage points (95% CI -18.3 to 18.3), risk ratio 1.00 (0.32–3.11); unadjusted two-proportion z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Oral Acetaminophen/Caffeine Group and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Need for Representation for Treatment of Headache With 28 Days

• 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:
  • Oral Acetaminophen/Caffeine Group: 4.3% (1/23) versus 20.8% (5/24) on control; risk difference -16.5 percentage points (95% CI -34.7 to 1.8), risk ratio 0.21 (0.03–1.65); unadjusted two-proportion z-test p = 0.090.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Oral Acetaminophen/Caffeine Group and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address a range of later events, including whether participants received additional treatment, needed consultation or admission, or returned for headache care. Across the numeric results posted for these outcomes, the pattern is not uniform: some contrasts are numerically in one direction, others show no observed separation, and the follow-up representation outcome uses smaller denominators than the primary comparison. These measures describe different stages of care and should not be treated as repeated measures of the same endpoint.

The secondary results do not overturn the primary interpretation. The primary endpoint asks whether participants met a defined headache-response threshold after initial treatment. Secondary measures capture subsequent care decisions or events, which can depend on factors beyond that initial response. Their results can provide context, but they do not independently resolve the uncertainty in the primary comparison.

The registry record lists 13 secondary outcomes, while numeric results are posted for only some of them. Conclusions about the overall pattern must therefore remain limited to results actually reported. The registry record does not explain the reasons for outcomes without posted numeric results or identify which secondary outcomes, if any, were designated as especially important in the analysis plan.

Multiple secondary comparisons increase the chance that at least one result may appear notable by chance, particularly when many outcomes are examined without an adjustment for multiplicity. No multiplicity adjustment is reported. For that reason, unadjusted secondary findings carry less inferential weight than a clearly prespecified primary endpoint and should be viewed as exploratory context rather than as independent confirmation. The registry record also does not report whether these analyses were prespecified or how their interpretation was prioritized.

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

• Response to Treatment Within 2 Hours
• Number of Participants With Need for Crossover Treatment
• Response to Cross Over Treatment at 60 Min
• Number of Participants With Need for Second Line Treatment
• Response to Second Line Treatment at 60 Min
• Number of Participants With Need for Neurology Consult
• Number of Participants With Need for Admission for Treatment of Headache
• Number of Participants With Need for Representation for Treatment of Headache With 28 Days

9. Statistical Interpretation

10. Statistical Methods Explained

What does the randomized comparison estimate?

Random assignment creates a basis for comparing groups because assignment, rather than participant or provider selection, determines which treatment is offered. In a parallel-group trial, each participant is assigned to one group and outcomes are compared between groups. Randomization does not guarantee that every measured or unmeasured characteristic is identical across groups, particularly in a trial of this size, but it is the design feature intended to reduce systematic allocation differences.

The posted primary measure is binary: each participant either meets the response definition or does not. A risk, in this setting, is the proportion of participants in a group who meet that definition. The risk difference compares those proportions by subtraction. The recalculated difference is reported as oral treatment minus occipital nerve block, so a negative value indicates a lower observed response proportion in the oral group. This is a simple, unadjusted comparison based on the posted counts.

What does the reported test tell the reader?

The registry record reports a chi-squared test for the primary comparison. In general, a chi-squared test assesses whether the observed distribution of a categorical outcome differs across groups, under assumptions that include independent observations and adequate expected cell counts. The p-value describes how unusual results at least as discrepant as those observed would be under the test’s null model. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result was caused by chance.

The sponsor-reported p-value is 0.30. The posted unadjusted recalculation is p = 0.303. The small difference in displayed precision does not change the broad interpretation. The registry record does not report a prespecified significance threshold or further details of the sponsor’s statistical plan, so the test result is best read as the reported comparison rather than as evidence that all analysis choices are known.

Why consider an effect estimate and an interval as well?

A p-value alone does not show the estimated size of a difference or the range of values reasonably compatible with the data. The risk difference provides an absolute-scale estimate, while its confidence interval conveys uncertainty around that estimate. A confidence interval is formed by a statistical procedure that, under its assumptions, would cover the target value at its stated confidence level over repeated samples. It is not a guarantee that the true value lies in the particular interval, nor does it describe the spread of individual participant outcomes.

The comparison also reports relative measures, including a risk ratio and an odds ratio. In general, a risk ratio compares group proportions as a ratio, while an odds ratio compares the odds of the outcome. These are different scales for expressing a binary contrast and can be less intuitive than an absolute risk difference. The registry’s posted relative estimates are unadjusted. They should not be treated as adjusted for baseline characteristics or other covariates.

Why can over-dispersion matter?

Over-dispersion occurs when the observed variability is greater than a statistical model expects. It matters in models that rely on a specified variance structure, because underestimated variability can produce confidence intervals that are too narrow and p-values that are too small. The primary outcome is a binary participant count, and the registry reports a chi-squared comparison rather than a count model requiring an over-dispersion assessment. The registry record does not report a separate over-dispersion analysis or a model-based adjustment. This general concept should not be taken to mean that over-dispersion was identified in this trial.

Why does the choice of test vary for secondary outcomes?

The registry lists chi-squared and Fisher exact tests for the reported comparisons. Fisher’s exact test calculates a probability-based comparison for categorical counts and is commonly used when cell counts are small. The record uses it for the second-line treatment and representation outcomes, while chi-squared tests are reported for the primary endpoint and crossover outcome. Differences in test choice can affect p-values, especially with sparse data, so the test reported for each comparison matters. No adjusted analyses are listed for these outcomes.

For the primary outcome, the recalculation uses posted group counts and is unadjusted. It does not reconstruct an unreported model, account for unreported baseline factors, or resolve uncertainty about missing outcomes. The registry record does not report whether adjustments were planned, how missing observations were handled, or whether all randomized participants were included in each analysis. Those omissions limit how fully the methods can be assessed.

11. Confidence Intervals and Precision

The primary group counts are 20 responses among 31 participants assigned to occipital nerve block and 16 among 31 assigned to oral acetaminophen/caffeine. The recalculated risk difference is -0.129 for oral treatment compared with nerve block. The confidence interval for that contrast includes zero. In general, this means that the observed data do not rule out no difference at the interval’s confidence level, and they also allow values on either side of no difference.

The interval is wide enough to leave substantial uncertainty about the magnitude and direction of the contrast. It is therefore important not to treat the point estimate as a precise estimate of the underlying group difference. The observed counts show a numerical separation, but the uncertainty interval indicates that the trial’s data are compatible with more than one interpretation of the population contrast.

Confidence intervals express uncertainty in an estimate under the method’s assumptions; they do not show the range of outcomes among individual participants. Nor do they account automatically for limitations such as unreported missing-data handling, possible outcome assessment effects in an open-label trial, or unreported analysis choices. The interval should be interpreted together with the study design and the limitations of the registry record.

The relative effect estimates are also uncertain, with their posted intervals spanning the null value for those measures. Whether the comparison is expressed as an absolute difference or on a relative scale, the available results do not identify a narrow, stable estimate. More participants can generally improve precision, but the observed interval alone does not dictate what a future study would find.

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 planning figures are illustrations based on the observed effect, not the trial’s original design calculation. The original sample-size justification and its assumptions are not reported in the registry record. For these binary outcomes, the figures represent participants per arm, not a combined total. The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planning effect is set to the stated fraction of the observed effect.

The column for 80% power gives the estimated participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one and the analysis assumptions held. The 90% power column expresses the corresponding planning target for a 90% chance of detection. These are design probabilities for a hypothetical future study; they are not probabilities that the observed trial result is correct.

The listed rows consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. A smaller effect is harder to distinguish from random variation, so planning for a smaller effect requires more participants per arm. The figures also depend on the effect estimated from this trial, which is itself uncertain. They should be read as sensitivity illustrations rather than as definitive enrollment recommendations.

These calculations are not observed power. Observed power is not a useful substitute for interpreting the estimate and its confidence interval after a trial is complete. The posted planning figures describe hypothetical future designs under stated assumptions; they do not alter the uncertainty in the results already observed.

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 = 0.645; treatment proportion p₁ = 0.516; average p̄ = 0.581.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6978 = 1.3678.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6919 = 0.5823.
4. n = (1.3678 + 0.5823)² / (-0.1290)² = 228.4, rounded up to 229 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 <- 0.645161290322581                          # control proportion
p1 <- 0.516129032258065                          # 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(3951649)
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 = 229 (80% power), 306 (90% power)
 75% of observed effect: n per arm = 403 (80% power), 538 (90% power)
 50% of observed effect: n per arm = 894 (80% power), 1,196 (90% power)
power.prop.test: 228.4 
Simulated power at n = 229 per arm: 0.803 (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. Analyses Reported by the Sponsor

The registry-reported primary analysis uses a chi-squared test and gives p = 0.30. The simple unadjusted recalculation from the posted group counts gives p = 0.303 and a risk difference of -0.129 for oral treatment compared with occipital nerve block. The registry does not flag a discrepancy between the reported result and the recalculation. The values are close, with the small difference in p-value reflecting the displayed precision of the two results.

Both results support the same broad statistical reading: the posted primary comparison does not show clear evidence of a difference between groups. The recalculation offers an unadjusted effect estimate and confidence interval based on the summary counts; it is not a replacement for an analysis using any additional participant-level information or an unreported prespecified model. The sponsor-reported result remains the trial’s reported analysis, while the recalculation is a straightforward check on the posted summary statistics.

The registry record does not report details that would establish whether the sponsor’s analysis used covariate adjustment, how missing data were treated, or which analysis population was intended. No such features should be inferred from the p-value alone. The two displayed p-values are consistent in their broad interpretation, but neither establishes equivalence or determines the clinical importance of a possible difference.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures and 13 analyses, including multiple secondary outcomes and comparisons. Examining many outcomes creates a multiplicity issue: even if there is no true group difference for any outcome, the chance of at least one apparently unusual result rises as more comparisons are considered. A multiplicity procedure can adjust interpretation or testing to account for this, but the registry record does not report such an adjustment or a hierarchy for interpreting secondary outcomes.

The primary outcome is the central comparison, but the registry record does not provide a complete statistical analysis plan identifying which analyses were prespecified, how outcome definitions and timepoints were prioritized, or how testing across outcomes was to be handled. The reported p-values should therefore be read as individual comparisons, not as family-wise adjusted evidence. In particular, secondary results deserve caution when considered alongside many other outcomes.

Missing-data handling is also not reported. The primary results include 31 participants in each group, while the 28-day representation results use denominators of 24 and 23. The registry record does not state why those denominators differ from the primary outcome denominators, whether the difference reflects missing follow-up, eligibility for the outcome, or another reason, or how any missing observations were treated. No missing-data method should be assumed.

The record does not state whether the analysis population was intention-to-treat, per-protocol, or defined another way. Nor does it describe exclusions after randomization or how participants with incomplete outcome information were handled. These details matter because they affect which participants contribute to each estimate and can influence the interpretation of a randomized comparison.

Interim analyses, stopping rules, and the original sample-size justification are not reported in the registry record. These omissions do not establish that such procedures were or were not used; they mean the record does not allow their role to be assessed. Similarly, the registry record does not report adjustment for baseline variables, so the posted effect estimates should be treated as unadjusted unless further analysis details are available.

16. 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 3% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s serious adverse event figures report zero serious adverse events among 31 participants in the occipital nerve block group and zero among 31 participants in the oral acetaminophen/caffeine group. Deaths are reported as zero in both groups. For other adverse events, the record reports zero affected participants in the nerve block group and 3 in the oral treatment group.

These are counts in the trial record, not proof that serious events cannot occur or that the treatments have equivalent safety. With 31 participants per group, uncommon events may not be observed even if they are possible. The registry record does not provide further detail about the three other adverse events, their severity, timing, attribution, or whether they led to treatment changes.

Adverse-event counts should be interpreted as reported, without assuming that an event was caused by a study treatment. The record does not provide enough detail to assess completeness of event collection or the definitions used for all categories. The figures describe what was posted for this trial, not a comprehensive estimate of risks in a broader population.

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

The primary result describes the proportion of participants who met a particular headache-response definition at the reported assessment. The observed counts were 20 of 31 after occipital nerve block and 16 of 31 after oral acetaminophen/caffeine. The unadjusted risk difference is -0.129 when expressed as oral treatment minus nerve block, and the confidence interval includes zero. The sponsor-reported p-value is 0.30. Together, these results indicate uncertainty about the size and direction of the difference in this trial.

The result does not show that the treatments are equivalent. Equivalence requires a design and analysis with a prespecified equivalence margin, and no such margin is reported in the registry record. A non-significant comparison also does not demonstrate that there is no difference. It means that the reported analysis did not provide clear evidence against its null comparison at the level of precision available.

Nor does the result establish that one treatment is better or worse in a broad clinical sense. The endpoint is a binary response threshold, rather than a complete assessment of pain experience, duration of relief, recurrence, or every aspect of care. The secondary outcomes add information about some subsequent events but are limited by multiplicity and incomplete numeric reporting.

The open-label design is relevant because participants and providers knew the assigned treatment. Headache response includes a subjective assessment, so awareness of treatment could potentially influence reported experience or assessment. The registry record does not quantify whether or how such effects occurred. Randomization helps support the group comparison, but it cannot remove every possible source of measurement or implementation bias.

Finally, the results apply to the trial’s enrolled participants and recorded follow-up. Eligibility criteria, fuller population characteristics, missing-data methods, and analysis-population definitions are not reported in the registry record. The posted findings should therefore be understood as an estimate with uncertainty from this trial, not as a definitive statement about every pregnant patient with headache or every treatment setting.

18. Why This Trial Matters Statistically

This trial is statistically informative because it puts a subjective symptom outcome into a defined comparison: the proportion of participants reaching a specified headache-response threshold after randomized assignment. Translating a response criterion into group counts makes the contrast understandable, while the risk difference and confidence interval show that the observed difference is uncertain rather than self-explanatory.

The example also illustrates why the estimate, interval, and test result should be read together. The point estimate has a direction, but the interval spans no difference and values on either side. The reported and recalculated p-values tell a compatible story, yet neither p-value communicates the range of plausible effect sizes. Statistical interpretation is stronger when it describes all of these features rather than treating a significance threshold as a verdict.

Open-label trials of subjective outcomes raise particular questions about outcome assessment and expectations. The result is not automatically invalid because masking was absent, but the design feature belongs in the interpretation. The same applies to incomplete registry detail: absent information about analysis populations, missing data, multiplicity, and original planning assumptions limits the extent to which readers can audit the analysis.

The secondary endpoints further demonstrate how a trial can generate many different forms of evidence: immediate response, additional treatment, consultation, admission, and subsequent return for care. Those outcomes are related but not interchangeable. A transparent distinction between the primary question and exploratory or multiplicity-sensitive secondary findings helps avoid overstating a pattern.

Overall, this record is a useful illustration of reading a small randomized comparison with attention to absolute effects, uncertainty, design, and reporting gaps. The statistical lesson is not a treatment recommendation; it is that an observed difference and a non-significant test do not remove the need to examine precision and study limitations.

19. 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 result rests on 31 participants per group, so the estimated response difference is imprecise. The confidence interval includes zero and allows a range of possible contrasts. The trial’s enrollment and observed counts do not support a narrow conclusion about the magnitude of any underlying difference.

The open-label design is a particular limitation for a headache-response outcome, which depends on subjective symptom assessment. Participants and providers were not masked, and the registry record does not describe any safeguards intended to reduce the influence of treatment awareness on outcome measurement.

The primary timeframe is described as 60-300 min, while the outcome definition refers to assessment at 2 hours. The registry record does not explain this distinction. It also does not report detailed eligibility criteria, baseline headache characteristics, or other population information needed to judge how closely the enrolled participants represent a wider clinical population.

Analysis details are incomplete. The record does not report the intended analysis population, missing-data methods, original sample-size justification, interim analyses, or a full statistical analysis plan. The 28-day representation outcome has smaller denominators than the primary outcome, but the reason and treatment of missing observations are not stated. There are multiple secondary outcomes, and no multiplicity adjustment is reported.

The adverse-event summary provides counts but little detail on event type, timing, severity, attribution, or collection procedures. The registry record also contains an incomplete description of the nerve block procedure. These reporting limitations constrain interpretation; they do not by themselves establish that a particular bias or safety problem occurred.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Acute Headache Treatment in Pregnancy: Occipital Nerve Block vs PO Acetaminophen With Caffeine — NCT03951649.
• Registry record last updated 2023-12-20; status last verified 2023-11.
• Results first posted 2023-12-20.
• 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.

23. Record Summary

NCT03951649 is a completed, randomized, open-label, parallel-group Phase 4 trial sponsored by the University of Alabama at Birmingham. It enrolled 62 participants and compared occipital nerve block with oral acetaminophen 650mg and caffeine 100mg for acute headache in pregnant patients seeking care.

The primary endpoint counted participants with headache resolution or improvement to mild range at 2 hours; its timeframe is also listed as 60-300 min. The posted primary counts were 20 of 31 in the nerve block group and 16 of 31 in the oral treatment group. The sponsor-reported chi-squared p-value was 0.30, and the unadjusted recalculation gives p = 0.303 with a risk difference of -0.129 for oral treatment compared with nerve block. The confidence interval includes zero.

The record lists 14 outcome measures and 13 analyses. Numeric secondary results and adverse-event counts are posted, but details about missing data, analysis populations, multiplicity, and the original sample-size rationale are not reported in the registry record. The primary comparison is uncertain and should not be interpreted as proof of equivalence or as a definitive conclusion beyond the outcomes recorded.