Ibuprofen Plus Metaxolone, Tizanidine, or Baclofen for Low Back Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ibuprofen Plus Metaxolone, Tizanidine, or Baclofen for Low Back Pain (NCT03068897), a randomized phase 4 study. The primary outcome is Change in Functional Impairment as Measured by the Roland Morris Disability Questionnaire (RMDQ).

2. Clinical Question

The question is about the additional contribution of each muscle relaxant within a shared treatment context. It is not a comparison of muscle relaxant treatment with no treatment: ibuprofen and the educational intervention were part of every arm, including the placebo arm. The registry record identifies the study as randomized, with parallel groups and quadruple masking.

The primary endpoint was change in the Roland Morris Disability Questionnaire (RMDQ) from baseline to 7 days. The measure captures reported limitations in daily life related to low back pain. The posted results give a mean and 95% confidence interval for each arm, but do not report a direct two-arm comparison for this primary endpoint. The arm summaries therefore describe the observed changes but do not establish whether the randomized groups differed beyond what could plausibly arise from sampling variation.

The record also lists secondary questions about change in low back pain, need for medication, and disability levels. The posted numerical secondary results cover two of these topics; a numerical result for levels of disability is not reported in the registry record. The trial record reports an enrollment of 320, while the outcome summaries have arm-specific denominators. Those figures are not reconciled in the registry record, so they should be interpreted in their stated contexts rather than treated as interchangeable.

3. Trial Design

The registry record identifies NCT03068897 as a Phase 4 randomized trial with a parallel-group design and quadruple masking. Montefiore Medical Center is listed as the sponsor. The condition is low back pain, and enrollment is recorded as 320. The study status is completed. The recorded start date is 2017-05-03, and the primary completion date is 2018-07-11.

Participants were enrolled during emergency-department visits. The study compared three active add-on regimens with a placebo add-on regimen. In each active arm, participants received ibuprofen 600 mg together with metaxalone, tizanidine, or baclofen. In the comparator arm, participants received ibuprofen 600 mg with placebo. All arms included a brief educational intervention. The listed medications were to be taken as needed every 8 hours for 7 days.

This shared background treatment matters when interpreting the contrast: any arm-to-arm difference concerns adding a particular muscle relaxant to ibuprofen and education, rather than the effect of the full regimen compared with receiving no care. The placebo arm also received ibuprofen and education, so it serves as an add-on comparator.

The record describes follow-up for three months, while the primary outcome timeframe is baseline and 7 days. The listed secondary outcome timeframes include baseline and 7 days for change in low back pain, and 7 days for need for medication. The registry record does not report a detailed visit schedule beyond those descriptions. Nor does it report the method used to generate the random sequence, allocation concealment procedures, or which parties were included in the quadruple masking.

Outcome summaries list 76 participants for metaxalone, 76 for tizanidine, 79 for baclofen, and 74 for placebo for the primary endpoint. The secondary summaries use denominators that differ in some instances from the primary summaries. The adverse-event summaries list 80 at risk in each arm. These numbers describe different posted outcome records; the registry record does not explain the differences or provide a participant-flow account that reconciles them with the recorded enrollment.

No protocol details about treatment adherence, rescue treatment, co-interventions, or the handling of treatment discontinuation are reported in the registry record. Those omissions limit how fully the treatment contrast and the observed outcome summaries can be reconstructed from the record alone.

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 Change in Functional Impairment as Measured by the Roland Morris Disability Questionnaire (RMDQ), measured over Baseline and 7 days.

The primary endpoint is change in functional impairment measured with the Roland Morris Disability Questionnaire (RMDQ), from baseline to 7 days. The RMDQ contains 24 items about the impact of low back pain on daily life. Each item is answered yes or no, and the total score ranges from 0 to 24. Higher scores indicate greater impairment and worse quality of life, as described in the registry record.

Change was calculated as the baseline score minus the score one week after discharge. With that subtraction order, a positive change means the follow-up score was lower than baseline, which corresponds to reduced reported impairment. A value nearer zero would indicate less change in score. This direction is important: the endpoint is not the follow-up score alone, and its sign should be read using the specified baseline-minus-follow-up definition.

The measure is used because it captures functional limitations associated with low back pain, rather than pain intensity alone. The registry description says it is most sensitive for people with mild to moderate disability due to acute, sub-acute, or chronic low back pain. It is a self-reported measure, and the posted endpoint is summarized as a mean change in units on the scale, with 95% confidence intervals.

The endpoint is measured at a short-term follow-up, despite the study description indicating that participants were followed for three months. The registry record does not report a primary outcome measurement at the end of that longer follow-up period. The posted mean changes therefore address the specified 7-day outcome and should not be read as a summary of longer-term functional status.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score change on the RMDQ. The registry record summarizes each arm with a mean and a 95% confidence interval. A mean describes the average change in the arm, while the confidence interval conveys uncertainty in estimating that mean from the observed participants. In general, a confidence interval is not a range containing a stated proportion of individual participants; it concerns uncertainty around an estimated quantity under the assumptions of the method.

The registry’s interval summaries are not treatment-effect intervals. To evaluate whether adding a muscle relaxant changed the outcome relative to placebo, the relevant quantity would be a direct contrast between the mean changes in those randomized groups, along with uncertainty for that contrast. A direct comparison can have different precision from either arm’s separate interval. The registry record does not report such primary contrasts, so the arm means and their intervals cannot stand in for a comparative analysis.

The score’s direction also affects interpretation. The endpoint is defined as baseline score minus the score at one week after discharge. A positive value therefore corresponds to a lower score at follow-up. Because higher RMDQ scores mean greater impairment, this is a reduction in impairment score. The summary remains an average: participants can have different changes, and the group mean does not describe the full distribution.

What do the secondary risk differences represent?

The two posted binary secondary outcomes count participants meeting the outcome in each arm. Their accompanying recalculated comparisons express risk differences: the proportion with the outcome in an active arm minus the proportion in the placebo arm, using the posted counts and denominators. A risk difference is on an absolute scale. A value near zero indicates similar observed proportions, while a positive or negative value indicates the direction of the observed difference under the stated subtraction order.

The record also contains recalculated relative measures for these outcomes, but these are simple, unadjusted calculations from the posted summary counts. Such measures describe the observed groups and do not adjust for covariates or account for analysis choices not represented in the summaries. The recalculated confidence intervals and p-values are not reported analyses from the trial sponsor. The registry record lists no reported analyses for these secondary outcomes. As a general principle, a confidence interval for a risk difference that includes zero is compatible with no difference as well as with effects in either direction allowed by the interval.

These recalculations should be treated as descriptive aids, not as a replacement for a prespecified trial analysis. They cannot establish whether a comparison was planned, whether adjustments were intended, or how multiplicity was addressed. Those details are not reported in the registry record. Where no sponsor analysis is posted, the recalculated quantities should be understood as unadjusted estimates based on the available summary data.

How should the planning illustrations be read?

The sample-size illustrations are planning calculations based on observed secondary-outcome effects, not a record of the trial’s original design. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The figures are participants per arm for the stated power level. They are not observed power, and they do not tell how likely the completed trial was to detect the true effect.

Observed effects can be unstable, especially when estimated from a limited dataset. A planning illustration that takes an observed effect as its target inherits uncertainty in that estimate. Reducing the target effect to a fraction of the observed estimate increases the planning requirement in the posted illustrations, but those figures remain conditional on the stated assumptions. They are not a recommendation for a future trial and should not be mistaken for the actual enrollment rationale.

The registry record does not report the protocol’s sample-size justification, the primary-outcome assumptions used in planning, or any planned interim analyses. The posted illustrations concern two-arm binary comparisons for secondary outcomes, whereas the primary endpoint is continuous. They therefore do not supply a sample-size analysis for the primary RMDQ comparison.

Why does unadjusted analysis matter?

Randomization supports a causal comparison in expectation when the assigned groups are analyzed appropriately, but a registry summary alone does not show which analysis population or model was used. Adjustment may be prespecified to account for baseline measurements or other variables, and the appropriate choice depends on the protocol and analysis plan. Neither a covariate-adjusted model nor a model specification for the primary endpoint is reported in the registry record.

Unadjusted recalculations are transparent in a limited sense: they are based on the posted group counts and denominators rather than unavailable individual-level data. But they cannot account for missing outcomes, clustering, stratification, or other design and analysis features unless those are explicitly represented. There is no basis in the registry record for asserting that such features applied; equally, there is no basis for assuming they did not. The distinction is between what can be calculated from posted summaries and what the trial’s own statistical analysis may have specified.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a prespecified testing hierarchy, or a multiplicity adjustment. It lists several outcomes and multiple active-versus-placebo comparisons. When multiple hypotheses are examined, the chance of at least one apparently unusual result can increase; this is a general statistical issue, not a finding about the conduct of this trial. Without a reported plan, it is not possible to determine whether the posted secondary comparisons were confirmatory, exploratory, or adjusted for the number of tests.

No sponsor-reported analyses are listed for the posted outcomes. The recalculated secondary comparisons are unadjusted calculations based on summary counts. The primary RMDQ endpoint has arm-level descriptive summaries but no reported two-arm analysis. The registry record does not report model specifications, covariate adjustment, the approach to repeated measurements, or whether baseline outcome values were incorporated into a comparison.

Missing-data handling is also not reported. The outcome summaries have denominators that differ across outcomes and from the recorded enrollment; the adverse-event summaries use a further denominator. The record does not provide a participant-flow account, reasons for missing measurements, imputation methods, or sensitivity analyses. The observed denominators alone do not reveal whether people lacked a measurement, were excluded from an analysis, or were handled in another way.

Analysis populations are not identified. The registry record does not state whether results use an intention-to-treat population, a per-protocol population, or another definition. It also does not report adherence or discontinuation summaries that could clarify the relation between assigned treatment and analyzed outcomes. These omissions matter because the interpretation of a randomized comparison depends on who is included and how outcomes that are unavailable are handled.

Interim analyses and stopping rules are not reported in the registry record. The sample-size rationale for the original trial is also not reported; the posted planning illustrations are based on observed secondary effects and are not evidence about the trial’s original design. These missing details do not prove that specific methods were absent. They mean only that the registry record does not allow those methods to be evaluated.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The adverse-event summary records zero serious adverse events in each arm and zero deaths in each arm. It lists 80 participants at risk in each arm for the serious-event and other-event summaries. These are the figures recorded in the registry and should be read as counts for the stated risk groups, not as proof that no serious events could occur with these regimens.

The record also lists 6, 6, 7, and 5 participants affected by other adverse events in the metaxalone, tizanidine, baclofen, and placebo groups, respectively. The registry record does not provide event descriptions for these other events in the posted summary. It lists no serious-event terms. Consequently, the types, severity beyond the serious/non-serious classification, timing, and relationship to study treatment cannot be characterized from these figures.

Zero recorded serious events in an arm is not the same as establishing zero risk. A trial’s ability to characterize uncommon harms depends on the amount and duration of observation and the completeness of event reporting. The registry record does not provide enough detail to assess those aspects fully. Nor does it report a comparative safety analysis. These counts are descriptive and should not be interpreted as demonstrating that the regimens have identical safety profiles.

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

The primary results describe average 7-day changes in functional impairment scores within each randomized arm. Because the change is calculated as baseline minus follow-up, positive mean values correspond to lower RMDQ scores at follow-up. This is a statement about the direction of the posted group summaries, not a conclusion that every participant improved or that the active regimens caused the observed change.

The central comparative question is whether adding a muscle relaxant changed the outcome relative to ibuprofen, placebo, and education. The registry record does not provide a direct primary comparison estimate or its uncertainty. Arm means should not be treated as if they were treatment effects, and the overlap of their confidence intervals is not a formal test of between-arm differences. The primary endpoint’s comparative result is therefore not reported in a form that supports a precise conclusion from this record.

The secondary summaries are also limited. They cover two listed outcomes, use unadjusted recalculations for comparisons, and do not include a reported sponsor analysis. Their uncertainty and the absence of reported multiplicity procedures mean that they are best understood as exploratory descriptive evidence. The registry record does not post a numerical result for the listed levels-of-disability outcome.

These limitations do not establish that the study found no difference, nor do they establish that treatments were equivalent. A failure to report a comparison is not a null result. Similarly, uncertainty intervals that include no difference do not prove there is no effect. To assess whether a meaningful difference is compatible with the data would require a direct estimate, an appropriate interval, and a prespecified threshold for clinical importance. The registry record does not report a threshold for meaningful RMDQ change.

The results also concern a specific treatment context: ibuprofen with an add-on drug or placebo, alongside education, in participants enrolled during emergency-department visits. They do not directly answer questions about muscle relaxants used alone, other background treatments, other populations, or outcomes beyond those reported. The primary result is short-term, with the endpoint measured at 7 days. Although the study description mentions three months of follow-up, the registry record does not provide a primary long-term outcome summary.

In practical statistical terms, the record is more informative about what was measured and the arm-level outcomes than about the comparative primary effect. A complete interpretation would require the trial’s analysis plan, participant flow, handling of missing data, and direct between-arm estimates. Those details are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between reporting outcomes by arm and reporting the randomized contrast. A randomized design is organized around comparisons between groups, but the primary endpoint results in the registry are presented as separate means with confidence intervals. Those summaries describe each arm; they do not provide the uncertainty around an active-versus-placebo difference. Readers should distinguish descriptive outcome reporting from a direct estimate of treatment effect.

The shared ibuprofen and education in all arms also makes the estimand specific. The comparison concerns the incremental effect of adding a muscle relaxant to that background regimen. It is not an estimate of the effect of a muscle relaxant in isolation. Clearly identifying the treatment contrast is essential to avoid attributing all observed change to the add-on drug when all arms received other study components.

The record also illustrates why a positive within-arm change is not, by itself, evidence of a comparative benefit. Several factors can contribute to changes over time, and the randomized contrast is intended to separate the effect of assigned add-on treatment from changes common to groups. Without the primary between-arm estimate, the record cannot show how precisely the groups differed.

Finally, the secondary outcome recalculations and sample-size illustrations demonstrate the distinction between exploratory calculations and a trial’s prespecified analysis. Planning values based on observed effects do not give observed power, and unadjusted comparisons do not establish the sponsor’s analytical conclusions. The registry record is useful for understanding the design and the posted data, while its missing analysis details limit the strength of statistical conclusions that can be drawn.

14. 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 are specific to the information recorded for this trial. The primary endpoint is summarized by arm, but the registry record does not report the direct comparisons required to answer the central randomized question. No primary contrast estimate, confidence interval for a contrast, or p-value is posted. The record also does not identify a threshold for a clinically important RMDQ change, so the clinical importance of any difference cannot be assessed from the posted summaries.

The record does not reconcile the enrolled population with the denominators used for the outcomes. The primary endpoint denominators are 76, 76, 79, and 74, while the adverse-event summaries list 80 at risk in every group. Secondary-outcome denominators also differ from the primary outcome denominators. Without participant flow and analysis-population definitions, the reasons for these differences cannot be determined.

Some listed outcomes are not accompanied by numerical results. In particular, the record lists levels of disability as a secondary outcome but does not post its results. The adverse-event summary gives counts but does not describe the other events or provide a comparative safety analysis. The registry record also does not report detailed demographic or baseline clinical characteristics, treatment adherence, or the handling of co-interventions.

Follow-up is described as lasting three months, but the posted primary endpoint is measured at 7 days. The record does not provide a primary outcome summary at the end of the longer follow-up. Thus, conclusions from the posted primary outcome are limited to the short-term measurement, and the longer-term course cannot be evaluated from that result.

Finally, the record does not include the statistical analysis plan, missing-data procedures, multiplicity strategy, or sample-size justification. The secondary recalculations are unadjusted and cannot resolve those gaps. These limitations concern what can be assessed from the registry record; they do not establish which methods were or were not used outside the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ibuprofen Plus Metaxolone, Tizanidine, or Baclofen for Low Back Pain — NCT03068897.
• Registry record last updated 2020-08-12; status last verified 2020-08.
• Results first posted 2020-08-12.
• 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.

18. Record Summary

NCT03068897 is a completed, randomized, parallel-group, quadruple-masked Phase 4 trial sponsored by Montefiore Medical Center. It enrolled people with low back pain during emergency-department visits and compared ibuprofen plus metaxalone, tizanidine, or baclofen with ibuprofen plus placebo. All arms included an educational intervention, and the listed medications were taken as needed for 7 days.

The primary outcome was change in RMDQ functional impairment from baseline to 7 days, defined as baseline score minus follow-up score. The registry reports arm-level means and 95% confidence intervals but no direct primary between-arm analysis. Two secondary outcomes have posted numerical summaries, while numerical results for levels of disability are not reported in the registry record. The record also lacks detail on the primary analysis, missing data, multiplicity, and reconciliation of outcome denominators.