Study To Investigate The Effectiveness Of Pregabalin For Management Of Patients Undergoing Total Hip Replacement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study To Investigate The Effectiveness Of Pregabalin For Management Of Patients Undergoing Total Hip Replacement (NCT00905437), a randomized phase 3 study. The primary outcome is Mean Pain on Movement Score.

2. Clinical Question

3. Trial Design

The registry describes a phase 3, randomized, quadruple-masked, parallel-group study of pregabalin versus placebo as an adjunct to standard of care. The listed enrollment is 72. The trial status is terminated. The record gives a start of 2009-11 and a primary completion date of 2012-07; it does not report why the trial was terminated.

The two arms were pregabalin and placebo. The official title describes a randomized, double-blind, multi-center study, while the masking field records quadruple masking. The registry record does not specify which roles were masked, so the masking label alone should not be used to infer the exact masking procedures.

The study focused on patients undergoing total hip arthroplasty and perioperative pain. The brief summary describes the intended treatment period as beginning a day before surgery and continuing for 14 days after surgery. Both study treatments were described as additions to standard care.

The listed primary outcome was mean pain on movement, defined using observations over Days 1 to 5 after surgery. Secondary outcomes listed in the registry include daily pain and sleep-interference scores, anxiety measured with an A-VAS, time to mobilization, rescue medication use, and neuropathic pain. The registry record reports selected results, but not results for every listed secondary outcome.

The primary outcome population was a modified intent-to-treat population, not simply every enrolled participant. It included randomized participants who had taken at least one pre-surgery dose and had no surgical complications; the analyzed number was the number evaluable for the measure. The registry record does not report the original sample-size justification or the reason for termination.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent to Treat (MITT) population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

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 Mean Pain on Movement Score, measured over Every 12 hours from Day 1 to Day 5 post-surgery.

The primary endpoint was mean pain on movement score. It was defined as the mean of pain-on-movement scores over Days 1 to 5 post-surgery, with assessments scheduled every 12 hours from Day 1 to Day 5. The score described pain during passive flexion through 90 degree and passive abduction through 30 degree at the operated hip joint.

The rating scale ran from 0, meaning no pain, to 10, meaning worst possible pain. A mean score condenses repeated ratings across the specified postoperative period into a single summary for each participant. Comparing group means gives a direct description of average scores during that period, though it does not show how individual scores changed over time or whether effects differed at particular assessment times.

Pain on movement is distinct from pain at rest: this endpoint concerns pain recorded during specified passive movement of the operated hip. The registry's measure is therefore tied to both the postoperative window and the movement procedure. The primary population excluded participants with surgical complications and required at least one pre-surgery study medication dose. Those eligibility rules matter when interpreting the group summaries: they describe the evaluable modified intent-to-treat population rather than necessarily every randomized participant.

7. Results Posted in the Registry

• Pregabalin: mean 4.00 versus 3.90 on control; difference 0.10 (95% CI -0.58 to 0.78), standardized effect d = 0.08; z-test p = 0.773.

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.

Mean Daily Sleep Interference Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Pregabalin: mean 2.60 versus 3.10 on control; difference -0.50 (95% CI -1.38 to 0.38), standardized effect d = -0.30; z-test p = 0.263.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pregabalin and the control. The interval gives the range of effects that remain compatible with the data.

Mean Anxiety Visual Analogue Scale (A-VAS)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Pregabalin: mean 23.30 versus 24.70 on control; difference -1.40 (95% CI -10.03 to 7.23), standardized effect d = -0.08; z-test p = 0.750.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pregabalin and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Rescue Medication Usage

• 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:
  • Pregabalin: 51.5% (17/33) versus 69.4% (25/36) on control; risk difference -17.9 percentage points (95% CI -40.7 to 4.8), risk ratio 0.74 (0.50–1.10); unadjusted two-proportion z-test p = 0.127.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pregabalin and the control. The interval gives the range of effects that remain compatible with the data.

The listed secondary outcomes cover several different aspects of recovery: pain scores, sleep interference, anxiety, mobilization, rescue medication use, and neuropathic pain. The registry posts numerical results for selected measures, including sleep interference, anxiety and rescue medication use, but does not post results for every listed secondary outcome. Mean daily pain, time to mobilization and the number of participants with neuropathic pain are listed outcomes whose results are not reported in the registry record.

Across the posted secondary comparisons, the point estimates do not all have the same direction or scale. They include continuous score differences and a binary risk difference, so they should not be treated as interchangeable measures of one underlying outcome. Their intervals express uncertainty for each outcome separately. None of these secondary summaries changes what the primary endpoint measured: movement-related pain averaged over its stated postoperative period.

Secondary results can help describe whether other outcome domains were also recorded, but they should be interpreted alongside the primary result and the registry's reporting limitations. The record lists no reported analyses for the secondary outcomes and does not describe a multiplicity adjustment. When several outcomes are examined, unadjusted results carry less weight as confirmatory evidence because considering multiple comparisons can increase the chance of apparently notable findings by chance. The registry record does not report whether or how the study's investigators addressed that issue.

These outcomes also differ in assessment windows and data types. For example, sleep interference and anxiety are continuous scores, while rescue medication use is reported as a participant count. Their estimates therefore answer different questions and should be read on their own scales and within their own time frames, rather than combined into a single overall treatment conclusion.

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

• Mean Daily Pain Score
• Mean Daily Sleep Interference Score
• Mean Anxiety Visual Analogue Scale (A-VAS)
• Time to Mobilization After Surgery
• Number of Participants With Rescue Medication Usage
• Number of Participants With Neuropathic Pain

9. Statistical Interpretation

10. Statistical Methods Explained

The main comparison is between two randomized parallel groups: pregabalin plus standard of care and placebo plus standard of care. Random allocation is intended to make the treatment groups comparable on average, while masking is intended to limit the influence of treatment knowledge on care, assessment or reporting. These are general purposes of trial design; the registry record does not provide further details about the procedures used to achieve them.

What the group means describe

The primary outcome is continuous: each participant has a score, and the registry reports the group mean. The pregabalin mean was 4.0 and its standard error was 0.23; the placebo mean was 3.9 and its standard error was 0.26. A standard error describes the precision of an estimated mean, not the amount of variation among individual participant scores. A standard deviation would describe individual-level spread, but the primary outcome is posted with standard errors.

The comparison is expressed as a mean difference of 0.1, with pregabalin as the first group and placebo as the reference group. This makes the direction interpretable: a positive difference means a higher average score in the pregabalin group, and a negative difference means a lower average score. Because higher pain ratings correspond to more pain on this scale, direction is important, but a point estimate should be considered together with its uncertainty.

How to read the confidence interval

A confidence interval gives a range of values compatible with the data under the method used. In general, a wider interval means less precision, and an interval spanning zero for a difference between means allows for both directions of difference. The primary interval is -0.580 to 0.780. It includes zero and permits differences on either side of zero. The interval does not state the probability that the true value lies within its particular bounds.

The registry also posts an unadjusted p-value of 0.773. A p-value describes how compatible the observed data are with a null model of no group difference, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an estimate. The record does not list a reported adjusted analysis for this outcome. The displayed p-value should therefore be treated as unadjusted rather than as an adjustment for other outcomes or analyses.

Population and evaluability

The primary outcome population is defined as a Modified Intent to Treat population. It includes randomized participants who took at least one pre-surgery study medication dose and had no surgical complications. The analyzed number is the number of participants evaluable for the measure. That definition narrows the population relative to a general description of all randomized participants, and it makes the outcome-specific analyzed counts relevant to interpretation.

The primary outcome counts were 27 in the pregabalin arm and 30 in the placebo arm. The registry record does not report how many participants were excluded for each reason, the amount or pattern of missing outcome data, or the method used to handle missing observations. Without those details, the group summaries cannot establish whether missingness or exclusions might have influenced the comparison.

What is and is not reported about analysis

The registry lists no reported analyses for the secondary outcomes, although it posts outcome summaries and comparisons for selected measures. This distinction matters: a result summary does not provide a complete account of the statistical model, covariate adjustment, repeated-measures method, or treatment of missing values. Those analytic details are not reported in the registry record.

The record does not report an interim-analysis plan, a multiplicity procedure, or a statistical analysis plan. It also does not report the original design assumptions used to select the enrollment target. The planning figures associated with the posted effects are separate illustrations based on specified assumptions, not evidence of the trial's original design process.

For the continuous outcomes, a mean difference is a natural way to express a contrast on the original measurement scale. For the binary rescue-medication outcome, the posted comparison is a risk difference, expressed as the difference in proportions between groups. General statistical reasoning applies to both: an estimate gives a direction and magnitude, while an interval communicates uncertainty. Neither a point estimate nor a p-value alone describes all relevant uncertainty or clinical importance.

11. Confidence Intervals and Precision

The primary mean difference was 0.1, with a 95% confidence interval from -0.580 to 0.780. This interval includes zero, so the posted data are compatible with no difference as well as with group differences in either direction. The range also shows that the estimate is not precise enough to pin down a narrow value for the underlying mean difference.

Confidence intervals are useful because they pair the estimated contrast with its uncertainty. In general, an interval is not a guarantee that the true value is within its endpoints, nor does it assign a probability to each possible value. Its interpretation depends on the method and assumptions used. The registry record gives the interval but does not report full details of the model or interval calculation.

The group means have standard errors of 0.23 for pregabalin and 0.26 for placebo. Standard errors describe uncertainty around the estimated means; they should not be mistaken for the range of scores among participants. The primary measure was available for 27 participants in the pregabalin group and 30 in the placebo group, within the defined evaluable population.

Precision is also distinct from clinical importance. The registry record does not report a clinically important difference threshold for the movement pain scale. As a result, the interval can be described statistically, but the record does not establish which values within it would be important to patients or clinicians.

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 derived from the observed effect, not the trial's original design justification. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. The original trial's own sample-size assumptions are not reported in the registry record.

For these outcomes, the figures refer to participants per arm, not a total across both arms. The sample-size display does not use a total-events convention; that convention applies to time-to-event calculations, and no time-to-event planning figure is being discussed. The columns for 80% and 90% power represent the number of participants per arm that the stated planning calculation estimates would be needed to have the corresponding chance of detecting the specified effect, if the assumptions were met.

Rows based on 100% of the observed effect use the full posted effect estimate as the target. Rows based on 75% or 50% use smaller target effects. Smaller effects are harder to distinguish from random variation, so the planning calculation calls for more participants per arm as the target effect becomes smaller. These estimates are illustrations, not proof that the observed estimates are stable or that a future study would have the assumed effect.

This is not observed power. It is a planning calculation using the posted effect and stated assumptions, and it should not be used to infer that the completed trial had a particular probability of detecting an effect.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.100; pooled standard deviation σ = 1.321.
2. n = 2 × (1.96 + 0.842)² × 1.321² / 0.100² = 2,738.5, rounded up to 2,739 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 <- 0.1                      # observed difference in means
sigma <- 1.32079727988267                     # 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(905437)
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 = 2,739 (80% power), 3,667 (90% power)
 75% of observed effect: n per arm = 4,869 (80% power), 6,518 (90% power)
 50% of observed effect: n per arm = 10,954 (80% power), 14,665 (90% power)
power.t.test: 2739.4 
Simulated power at n = 2,739 per arm: 0.796 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and multiple secondary outcomes, but it does not report a multiplicity adjustment or a hierarchy for interpreting the secondary comparisons. When multiple outcomes are tested, the chance of at least one apparently unusual result can increase. Adjustment procedures or a prespecified hierarchy can help control how those results are interpreted; whether such procedures were planned or used is not reported in the registry record.

The posted secondary p-values are unadjusted. They should not be read as if they account for all outcomes in the trial. The record also lists no reported analyses for the secondary outcomes, so it does not provide the full analysis details needed to assess modeling choices, outcome-specific hypotheses, or any prespecified decision rules.

Missing-data information is limited. The primary population required at least one pre-surgery dose and no surgical complications, and the analyzed count was the number evaluable for the endpoint. The record does not report how many participants were excluded under each criterion, why any outcome measurements were unavailable, or how missing values were handled. It does not report whether missingness differed between groups or whether sensitivity analyses were conducted.

The outcome counts vary by measure, which reinforces the need to interpret each result using its own analyzed population. Without details on the reasons for differences in evaluability, it is not possible to determine from the registry record whether the observed summaries could be affected by selection or missingness.

The registry record also does not report an interim-analysis plan, stopping rules, or a statistical analysis plan. It is therefore not possible to establish from this record which analyses were prespecified, how any planned interim monitoring was conducted, or whether the reported results represent all planned analyses.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: oxygen saturation decreased (2.9%), asthma (2.9%), hypotension (2.9%).

For serious adverse events, the registry reports 2 affected participants among 35 at risk in the pregabalin group and 0 among 37 at risk in the placebo group. These are counts within the reported safety populations. They should be read as descriptive event information, not as proof that treatment caused or prevented an event. The registry record does not provide a comparative statistical analysis of these counts.

The serious-event terms listed include oxygen saturation decreased, asthma and hypotension, each reported as 2.9%. The record does not provide further context about timing, severity beyond the serious-event classification, or causal attribution for these terms. Death figures are not reported in the registry record.

Other adverse events were reported for 23 of 35 participants receiving pregabalin and 22 of 37 receiving placebo. These broader counts are distinct from serious adverse events. Safety summaries describe what was recorded in the trial; by themselves, they do not establish whether events were related to study treatment or characterize risks outside the studied population and observation period.

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

The posted primary result estimates the difference in mean movement-related pain scores between the pregabalin and placebo groups over Days 1 to 5 after surgery. The point estimate is close to zero on the scale, but the confidence interval is broad enough to include differences in either direction. The statistical evidence should therefore be described as uncertain rather than as proof of equality or proof of a particular benefit or harm.

The result applies to the measure and population specified in the registry: participants who had taken at least one pre-surgery study medication dose, had no surgical complications, and were evaluable for the endpoint. It does not automatically describe all randomized participants, every person undergoing hip replacement, or outcomes beyond the stated assessment period.

The study summary also identifies anxiety, sleep disturbance and postoperative pain as areas of interest. The selected posted secondary outcomes provide additional descriptions, but the registry record does not report results for every listed outcome, and it does not report how multiplicity was addressed. Those gaps limit how broadly the results can be interpreted across different recovery domains.

Statistical uncertainty and clinical importance are related but not identical. A confidence interval describes uncertainty around an estimate, while clinical importance requires context about what size of difference matters. The registry record does not report a clinically important threshold for the pain scale, so the posted estimate cannot be judged against such a threshold from this record alone.

These findings describe the results as recorded, not a general treatment recommendation. The terminated status, limited details about missing data and analysis plans, and selected reporting of secondary outcomes should remain part of any interpretation. The record does not explain the termination, and no conclusion about its reason can be drawn from the status alone.

17. Why This Trial Matters Statistically

This trial illustrates why an estimated difference and its precision should be read together. A small point estimate can appear straightforward, but the confidence interval is essential for showing how much uncertainty remains about both direction and magnitude. The primary result makes that distinction visible: the estimate alone is not enough to establish a definitive interpretation.

It also highlights the importance of defining the analysis population. The registry's Modified Intent to Treat description excludes participants with surgical complications and requires at least one pre-surgery dose. The number analyzed is measure-specific. Those details affect the population to which the outcome summary applies and should not be obscured by the overall enrollment figure.

The record also demonstrates the difference between a trial's original design assumptions and a planning illustration based on observed results. The registry gives no original sample-size justification, while the accompanying planning estimates use explicit assumptions and observed-effect fractions. Treating those illustrations as an account of what investigators planned, or as observed power, would confuse two different statistical questions.

Finally, the multiple outcome domains make reporting discipline important. Several secondary measures are listed, but only selected results appear, and no adjustment approach is reported. That makes it important to distinguish exploratory description from confirmatory evidence and to avoid allowing one unadjusted secondary comparison to stand in for the primary trial question.

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.

The trial is marked terminated, but the registry record does not report why. The listed enrollment is 72, while the primary endpoint has measure-specific evaluable counts of 27 and 30 in the two arms. The record does not explain the exclusions or differences in evaluability, so their implications for the analysis cannot be assessed from the posted information.

The primary analysis population excludes randomized participants with surgical complications and requires at least one pre-surgery medication dose. This definition may be appropriate to the stated analysis, but it means that the primary summary does not represent every participant enrolled or randomized. The registry record does not describe additional analyses using a broader population.

Several design and analysis details are not reported in the registry record: the original sample-size justification, interim analyses, a statistical analysis plan, handling of missing data, and multiplicity procedures. The record also does not provide a clinically important difference threshold for the primary scale. These omissions limit assessment of prespecification, robustness, and clinical relevance.

Results are not posted for every listed secondary outcome. The available secondary summaries use different measures and time frames, and their p-values are unadjusted. The registry does not provide enough information to determine whether all planned secondary analyses are represented or how their results were intended to be interpreted together.

Finally, the primary endpoint covers movement-related pain over Days 1 to 5 after surgery. It does not by itself describe pain at rest, later recovery, or outcomes beyond the stated period. The record supports interpretation of the posted measures only within their specified populations and time frames.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study To Investigate The Effectiveness Of Pregabalin For Management Of Patients Undergoing Total Hip Replacement — NCT00905437.
• Registry record last updated 2021-01-28; status last verified 2021-01.
• Results first posted 2013-06-11.
• 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

The registry describes a phase 3 randomized, quadruple-masked, parallel-group trial of pregabalin versus placebo, each as an adjunct to standard of care, among patients undergoing total hip arthroplasty. Enrollment was 72, and the trial status is terminated. The record lists a start of 2009-11 and primary completion in 2012-07.

The primary outcome was mean pain on movement over Days 1 to 5 post-surgery. The posted means were 4.0 for pregabalin and 3.9 for placebo, with a mean difference of 0.1 and a 95% confidence interval from -0.580 to 0.780. The interval includes zero and allows differences in either direction.

Selected secondary outcome results and safety counts are posted, but results are not reported for every listed secondary measure. The registry record does not report the original sample-size rationale, missing-data methods, multiplicity procedures, interim analyses, or the reason the trial was terminated.