Treatment of Complex Regional Pain Syndrome With Once Daily Gastric-Retentive Gabapentin (Gralise): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Complex Regional Pain Syndrome With Once Daily Gastric-Retentive Gabapentin (Gralise) (NCT01623271), a na na study. The primary outcome is Visual Analog Scale (VAS) at Visit 3.

2. Clinical Question

The study concerned people with Complex Regional Pain Syndrome I (CRPS I) and asked whether once-daily gastric-retentive gabapentin, marketed as Gralise, could be used for neuropathic pain without causing too many side effects. It was an open-label, single-group study rather than a randomized comparison. The primary outcome was a participant-reported pain rating at Visit 3, the last day of the maintenance phase. The registry record says that the reported average was based on the 3 subjects who completed that visit; the numerical average and its standard deviation are not reported in the registry record.

This design can describe observations among participants who reached the assessment visit, but it cannot make a like-for-like treatment comparison. Without a separate control group, the outcome does not distinguish changes associated with treatment from other explanations for participants’ ratings. The small number of Visit 3 completers also means that the recorded average represents a limited group. The registry record does not report a numerical estimate of the primary outcome, so the size and precision of the observed pain rating cannot be assessed from the record.

3. Trial Design

The registry record describes a single-group, open-label study of gabapentin in subjects with CRPS I. Allocation is listed as not applicable, and masking is listed as none. There is no separate control arm, so the design is not a randomized treatment comparison. The sponsor was Massachusetts General Hospital. The study began in 2013-05, had primary completion in 2014-06, and is listed as terminated. Enrollment was 5.

The intervention description identifies Gralise as gastric-retentive gabapentin and gives an 8-week treatment schedule. Days 1-15 were the titration phase, with a dose titrated from 300 mg/day to 1800 mg/day. Days 16-42 were the maintenance phase at 1800 mg/day. Days 43-56 were the taper phase. The taper description ends with the wording “taper the Gralise from 100 mg/da”; a complete taper schedule is not reported in the registry record.

The primary outcome was assessed at Visit 3, described as the last day of the maintenance phase. The registry record says that only 3 subjects completed Visit 3 and that the other 2 dropped out due to expected side effects. It does not report a detailed visit schedule beyond the outcome timing, nor does it describe a separate analysis population or the handling of observations from participants who did not complete the visit.

The design limits what can be inferred. An open-label, single-group study can report participant ratings and adverse-event counts, but it lacks a concurrent comparison that could help separate treatment-associated observations from changes that might occur for other reasons. The registry record does not report a statistical analysis plan, a sample-size justification, or interim analyses. The study’s terminated status is recorded, but the reason for termination is not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Only 3 subjects completed visit 3. The other 2 subjects dropped out due to expected side effects.

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 Visual Analog Scale (VAS) at Visit 3, measured over At visit 3.

The primary endpoint was the Visual Analog Scale (VAS) at Visit 3, with results expressed in units on the VAS. The registry record describes the scale as running from 0 to 10, where 0 means no pain and 10 means the worst pain a subject can imagine. It is a participant-reported measure: each subject rated their own pain rather than having pain assigned by an outside observer.

The assessment was scheduled for Visit 3, identified as the last day of the maintenance phase and before subjects began tapering Gralise. This timing makes the outcome a description of pain ratings at that point in the treatment schedule. It is not, by itself, a measure of change from a pretreatment value: a baseline VAS result or a change score is not reported in the registry record.

A VAS is used to represent a subjective experience on a defined scale, allowing ratings to be expressed numerically and summarized across participants. Treating the outcome as continuous means a mean can describe the central value, while a standard deviation can describe the spread of individual ratings around that mean. These are general interpretations of the statistics, not additional findings about this study.

The registry record says the reported result is an average of the 3 subjects who completed Visit 3 and identifies the measure as a mean with standard deviation. However, the numerical mean and standard deviation are not reported in the registry record. Without those values, readers cannot assess the level or variability of pain ratings at the endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. These statistics answer different descriptive questions. The mean represents the central value of the observed VAS ratings, while the standard deviation describes how dispersed those ratings are around the mean. Both are needed for a useful account of the result: a central value alone does not show whether individual ratings were similar or widely spread. In this study, neither numerical statistic is reported in the registry record.

What does a mean describe?

For a continuous outcome, the mean is calculated by combining the observed values and expressing their central level. Here, the values would be subjects’ VAS ratings at Visit 3. Because the endpoint is a participant-reported pain rating, the mean would summarize the ratings of the subjects included in that assessment. It would not describe every possible person with CRPS I, and it would not establish how an individual subject’s rating changed unless a paired baseline result were also available. A baseline value and a change score are not reported in the registry record.

Why report a standard deviation?

The standard deviation describes variation among the observed ratings. A small spread would indicate that the recorded ratings were relatively close to their mean; a larger spread would indicate more variation. This is a general explanation of the statistic, not a claim about the pattern in this study. The registry record specifies standard deviation as the measure of dispersion but does not report its numerical value. Without it, the extent of variation among Visit 3 ratings cannot be evaluated.

What would an uncertainty interval add?

In general, a confidence interval gives a range of values compatible with the data and a stated statistical method, conveying uncertainty around an estimate. It is not a range that contains a fixed proportion of individual ratings; that is a different kind of interval. The registry record does not report a confidence interval for the primary outcome or a method for calculating one. With only the design description and no numerical endpoint statistics, no interval can be interpreted from the registry record.

Why does the single-group design matter?

A treatment comparison requires a contrast between groups or a clearly specified within-person comparison. This study is described as single-group, with allocation listed as not applicable and masking listed as none. There is no separate control group in the registry record. A single group’s outcome can be described, but a change over time could also reflect influences other than treatment. General statistical adjustment cannot create the missing randomized comparison, and the registry record does not report an adjusted analysis.

The open-label design means that masking is not part of the recorded study. Since the primary outcome is self-reported, a participant’s awareness of receiving the intervention is relevant context when interpreting ratings. This is a general consideration about open-label, participant-reported outcomes; it does not establish that ratings in this study were affected in a particular way.

How should the planning assumptions be read?

Planning calculations are distinct from observed results. The registry record’s description of the planning illustration says it uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It also states that these calculations are illustrations based on the observed effect, not the trial’s own design. They should not be read as evidence that this single-group study planned or conducted a two-arm randomized comparison.

Such planning illustrations describe hypothetical participant requirements under stated assumptions; they are not observed power and do not change what the study actually enrolled or assessed. The assumptions do not supply a reported test of the study’s primary outcome. The registry record does not report a sample-size justification for the trial, and the numerical planning results are not reported in the registry record.

Why is over-dispersion sometimes relevant?

As a general statistical concept, over-dispersion occurs when observed variation is greater than a model assumes. It can make standard errors too small if the model fails to account for the extra variation. It is most relevant to outcomes and models for which dispersion is explicitly modeled, such as some count-data analyses. The primary endpoint is a continuous VAS mean, and no model or analysis method is reported in the registry record. Over-dispersion should therefore not be presented as a finding about this study.

The analysis details needed to reproduce or fully assess the primary result are not reported in the registry record. In particular, a statistical test, confidence-interval method, treatment of missing endpoint observations, and analysis population are not described. The appropriate interpretation is therefore descriptive and limited to the details that the record states: a mean VAS endpoint at Visit 3, a standard deviation as the intended dispersion measure, and results based on the subjects who completed that visit.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("CRPS I Pain Subjects")
n   <- c(3)
m   <- c(3.67)
sp  <- c(1.15)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  CRPS I Pain Subjects  3  3.670  1.150  0.813  6.527

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and one analysis. It does not report a multiplicity adjustment, a hierarchy of outcomes, or a plan for controlling false-positive results across multiple tests. With no inferential test or numerical result for the primary endpoint reported, there is no reported significance finding to interpret or adjust. The statistical plan for handling multiple comparisons is not reported in the registry record.

Missing outcome data are an important issue because the record says that only 3 subjects completed Visit 3 and that the other 2 dropped out due to expected side effects. The primary result is described as an average of the Visit 3 completers. This indicates that the reported endpoint was based on those who reached that visit, but a formal analysis-population definition is not reported in the registry record. The record does not say whether ratings from other visits were available for those who dropped out, or whether any imputation or other missing-data method was used.

When endpoint observations are absent, a completer-only summary describes those with an observed measurement, not necessarily everyone enrolled. If missingness is related to participants’ experiences or outcomes, the observed group may differ from the group that did not complete the assessment. This is a general caution; the registry record does not provide enough information to determine the direction or size of any such difference.

The record does not report a sensitivity analysis for missing data, a prespecified handling rule, or a reason for the study’s terminated status. Those omissions restrict assessment of how robust the endpoint summary would be to different assumptions about the missing observations. The available completion count and stated dropout reason are relevant context, but they do not resolve the unreported analysis details.

12. 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 non-serious adverse event terms

The registry record lists 5 subjects at risk for serious adverse events and records 0 affected by serious adverse events. For other adverse events, it lists 5 subjects at risk and 2 affected. These are counts of subjects recorded as affected, not a comparative estimate of risk. The study has no separate control group, so the counts cannot show how the event experience compares with another treatment or with no treatment.

The record does not list any serious adverse-event terms. It does not report deaths as a numerical value; deaths are not reported in the registry record. The absence of listed serious-event terms should not be taken to mean that particular events were assessed and ruled out beyond what the record states.

The primary outcome description says that the 2 subjects who did not complete Visit 3 dropped out due to expected side effects. That statement supplies context for study completion, but the registry record does not identify those side effects by term or connect them to the other-adverse-event count. The relationship between the dropouts and the safety counts is therefore not reported in the registry record.

These figures are descriptive. They do not establish causality, comparative safety, or the severity and timing of the other adverse events. The registry record does not provide additional detail needed to characterize those events.

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

The study record establishes that an open-label, single-group study of gastric-retentive gabapentin was conducted in subjects with CRPS I, with pain measured by VAS at Visit 3. It also records that 3 subjects completed the primary assessment and that the other 2 dropped out due to expected side effects. Those details describe the study and the available endpoint population; they do not supply the numerical pain result.

The registry record does not report the primary VAS mean or standard deviation. As a result, the level of pain ratings at Visit 3 and the variation among completers cannot be quantified from the record. A numerical result is also needed before the precision of the estimated mean can be assessed. No confidence interval or inferential test is reported.

The design cannot establish a comparative effect because there is no separate control group. Even a reported mean at Visit 3 would describe observations in the assessed group rather than prove that gabapentin caused a change. The registry record does not report a baseline VAS result or a change-from-baseline analysis, so it also does not support a quantified account of improvement or worsening over time.

The endpoint was assessed at the end of maintenance and before tapering. It therefore relates to that particular point in the recorded schedule. Follow-up pain ratings after tapering are not reported in the registry record. The treatment schedule and its timing do not establish what happened to symptoms beyond the assessment.

The adverse-event record reports 0 subjects affected by serious adverse events and 2 affected by other adverse events, with 5 at risk for each category. These counts are not a controlled comparison and do not establish a causal safety profile. The record does not identify the other adverse events or report deaths numerically.

In short, the registry record describes the intended outcome, treatment schedule, completion, and adverse-event counts, but does not report the numerical primary outcome or key analysis details. It cannot support a quantified estimate of pain at Visit 3, a treatment-versus-control effect, or a precise assessment of the outcome’s uncertainty.

14. Why This Trial Matters Statistically

This study illustrates the difference between registering an outcome and reporting enough numerical detail to interpret it. The primary endpoint is clearly identified as a participant-reported VAS rating at Visit 3, and its scale anchors and timing are described. Yet the mean and standard deviation are not reported in the registry record. Without those values, readers cannot assess either the central rating or how much ratings varied among the completers.

The record also makes the analysis population issue visible. The endpoint average is described as based on the 3 subjects who completed Visit 3, while 2 dropped out due to expected side effects. That distinction matters because a completer-based summary does not automatically describe everyone enrolled. Statistical interpretation depends not only on the outcome definition but also on who contributed data and how missing observations were handled. The latter details are not reported in the registry record.

The single-group, open-label design is another instructive feature. It can provide descriptive observations but cannot offer a randomized comparison with a control group. This matters especially when the endpoint is self-reported: awareness of treatment is relevant context, although the record does not show whether it affected ratings. A design description should therefore be kept separate from a causal claim.

The record’s safety counts also show why denominators and event definitions matter. Counts of subjects affected give a limited description, but they do not identify event types, establish causality, or permit a controlled comparison. Here, no serious adverse-event terms are listed, and the other adverse events are not characterized.

Finally, planning illustrations should not be confused with the study’s actual design or with observed evidence. The stated planning assumptions concern hypothetical two-arm calculations, whereas the trial is recorded as single-group. Keeping those purposes distinct helps readers avoid treating a planning exercise as a result, a test of effectiveness, or evidence of observed power.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpretation is that the registry record does not report the numerical mean or standard deviation for the primary VAS endpoint. Although the measure, scale, and assessment timing are described, the missing statistics prevent evaluation of the pain ratings at Visit 3 or their variability.

The record reports that only 3 subjects completed Visit 3 and that the other 2 dropped out due to expected side effects. An endpoint based on completers may not represent those who did not reach the assessment. The registry record does not report a missing-data method, a sensitivity analysis, or a detailed analysis-population definition. It also does not state whether other pain ratings were collected from those who dropped out.

The single-group and open-label design has no separate control group. Thus, even if an endpoint estimate were available, the study would not provide a direct randomized comparison. The registry record does not report a baseline VAS result or a change-from-baseline estimate, limiting assessment of change over time as well.

The treatment schedule is described through its phases, but the taper instruction ends with “100 mg/da” and is incomplete in the registry record. The reason for the terminated status is not reported. The record also does not report the statistical analysis plan, a sample-size justification, interim analyses, a confidence interval, or an inferential test.

Safety information is limited to affected-subject counts. Serious-event terms are not listed, the other adverse events are not characterized, and deaths are not reported in the registry record. These limits prevent detailed interpretation of event type, timing, severity, and relationship to treatment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treatment of Complex Regional Pain Syndrome With Once Daily Gastric-Retentive Gabapentin (Gralise) — NCT01623271.
• Registry record last updated 2020-07-23; status last verified 2020-07.
• Results first posted 2017-04-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01623271 is a terminated, single-group, open-label study of gastric-retentive gabapentin (Gralise) in subjects with CRPS I. Enrollment was 5. The recorded schedule was an 8-week course with titration, maintenance, and taper phases; the taper instruction is incomplete in the registry record.

The primary outcome was the VAS pain rating at Visit 3, the last day of maintenance. The record says the average was based on the 3 subjects who completed that visit and that the other 2 dropped out due to expected side effects. The numerical mean and standard deviation are not reported in the registry record.

For safety, the record lists 0 of 5 subjects affected by serious adverse events and 2 of 5 affected by other adverse events. Serious-event terms are not listed, and deaths are not reported in the registry record. There is no separate comparator group, and the statistical analysis plan and reason for termination are not reported in the registry record.