Study Evaluating Dexketoprofen Trometamol/Tramadol Hydrochloride Analgesic Efficacy in Acute Low Back Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating Dexketoprofen Trometamol/Tramadol Hydrochloride Analgesic Efficacy in Acute Low Back Pain (NCT05170841), a randomized phase 4 study. The primary outcome is Time to First Achieve a Numeric Rating Scale-Pain Intensity Score <4 or a Pain Intensity Reduction of ≥30% From Drug Intake Till 8 Hours After the First Dose.

2. Clinical Question

This is a question about the timing of a defined pain-response threshold, rather than simply the average pain score at a particular time. A shorter time would indicate that the threshold was reached sooner among the observations included in the analysis. The outcome combines two ways to meet the response definition: reaching a pain-intensity score below 4, or reducing pain intensity by at least 30% from the score at drug intake. A patient can meet either condition.

The comparison is complicated by the trial’s staged treatment descriptions. Some groups received placebo only during the single-dose phase and active treatment during the multiple-dose phase, while the first 8 hours are the period relevant to the primary endpoint. The exact treatment contrasts intended for the primary statistical test are not fully described in the registry record. The registry also notes that tramadol hydrochloride 100 mg was not applicable to the primary outcome because the primary objective concerned the combination. These details matter when interpreting the reported test: the p-value alone does not reveal the size or direction of a specific contrast.

3. Trial Design

NCT05170841 is a completed Phase 4 randomized, quadruple-masked, parallel-group study sponsored by Menarini International Operations Luxembourg SA. The registry reports enrollment of 538. The study started on 2020-09-17 and the primary completion date was 2022-05-04. Its stated focus was analgesic efficacy and safety in patients with moderate to severe acute pain associated with acute low back pain.

The intervention descriptions distinguish a single-dose phase, from time 0 to 8 hours, and a multiple-dose phase, from 8 hours to Day 5. The active treatments were dexketoprofen trometamol 25 mg with tramadol hydrochloride 75 mg and tramadol hydrochloride 100 mg. Placebo was also used. The registry describes four treatment arms overall, including regimens that began with placebo during the single-dose phase and switched to active treatment during the multiple-dose phase. Thus, the treatment received during the first 8 hours was not necessarily the same as the treatment received later.

The primary outcome concerns the first 8 hours after the first dose. Its population description refers to a modified intent-to-treat population from the first cohort randomized to the four treatment arms in a 4:4:1:1 ratio. It also says tramadol hydrochloride 100 mg was not applicable to the primary outcome. The registry lists primary-outcome results for three groups, with the time-to-response measure reported as a mean and full range. The group results and a test are posted, but no estimated contrast, confidence interval, or detailed account of the test’s statistical implementation is given.

For secondary outcomes, the registry lists measures of total pain relief over specified time windows. The posted numeric summaries described in the statistical results include comparisons of the combination with tramadol during the single-dose phase. Details such as the randomization sequence, allocation concealment, masking procedures, protocol deviations, and the rationale for the enrollment target are not reported in the registry record. They should not be inferred from the design labels 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.

Single Dose Phase

Reasons for not completing this period:

Multiple Dose Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified intent-to-treat (mITT) population included the first cohort of patients randomized to the 4 treatment arms in a 4:4:1:1 ratio. Tramadol Hydrochloride 100 mg is not applicable for primary outcome measure since the primary objective was "To evaluate the analgesic efficacy of Dexketo/Tram fixed combination versus placebo in moderate to severe acute low back pain after the first dose (first 8 hours)"

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.

Population: The study encompassed 2 phases: * Single-dose phase (first 8 h) is BASELINE * Multiple-dose phase starting after the single-dose phase (from t8h until Day 5). In the single-dose phase, the patients received a single-dose treatment. In the multiple-dose phase patients assigned to DKP.TRIS / TRAM.HCl or TRAM.HCl previously continued the same treatment while patients assigned to placebo either received DKP.TRIS / TRAM.HCl or TRAM.HCl 100 mg during the multiple-dose phase.

6. Primary Endpoint

The registry lists the primary outcome as Time to First Achieve a Numeric Rating Scale-Pain Intensity Score <4 or a Pain Intensity Reduction of ≥30% From Drug Intake Till 8 Hours After the First Dose, measured over 8 hours from first intake (referring to first 8 hours of Single Dose Phase).

The primary endpoint is time from drug intake to first meeting a pain-response threshold during the first 8 hours after the first dose. The threshold is defined as either an NRS-PI score below 4 or a reduction in pain intensity of at least 30%. The registry describes the NRS-PI as an 11-point patient-rated scale, where 0 means no pain and 10 means worst pain. The endpoint is reported in hours, with a mean and full range for each listed group.

A time-to-response measure captures when a response first occurs, rather than only whether a response is present at a single scheduled assessment. This can be useful when the speed of symptom change is part of the research question. The threshold also makes the endpoint easier to interpret than a small change in a scale score alone: it identifies a specified level or proportional reduction in pain intensity. That is a general explanation of this type of endpoint, not evidence that the threshold is clinically important for every patient.

There are interpretive limits. The registry’s description does not specify how a participant who never met the threshold within the observation window was handled in the mean and range analysis. It does not report the assessment schedule, the handling of missing pain ratings, or a time-to-event model. The title refers to time to first achievement, but the posted parameter is a mean with full range and the reported test is labeled a two-sided t-test. Those labels do not establish that a particular survival-analysis method was used.

The registry presents values for three groups and a p-value, but no effect estimate or confidence interval. Consequently, the p-value cannot show how much earlier or later the threshold was reached, or how precise a specific treatment contrast is. The outcome’s definition is clear enough to state the question, but the full analysis details and treatment-specific effect estimates are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a time measure: time from drug intake until the first recorded achievement of either pain threshold during the first 8 hours. In general, time-to-event outcomes can be analyzed by methods that account for event timing and for participants who do not experience the event during observation. The registry, however, reports a mean and full range and labels the primary test as a two-sided t-test. It does not report whether any time-to-event method, censoring rule, or special handling of participants without a recorded response was used. A method should not be inferred from the endpoint title alone.

What does the primary p-value tell us?

The primary p-value is reported as 0.566 for a two-sided test across the listed groups. In general, a p-value describes how incompatible the observed data are with a specified null model, assuming the model and test conditions hold. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. Because the registry does not report an effect estimate or confidence interval for this primary test, the p-value cannot tell readers which contrast drove the result, how large a contrast might be, or how precisely it was estimated.

The registry labels the method a t-test, but its primary results include three groups. The exact test specification, contrasts, and adjustment for any multiple comparisons are not reported in the registry record. This prevents a full independent reconstruction of the primary analysis from the posted summaries.

How should the secondary mean differences be read?

For each posted TOTPAR comparison, the recalculated mean difference is expressed as tramadol minus the combination. The negative sign therefore indicates that the posted tramadol mean is lower than the combination mean. The accompanying confidence interval describes a range of effect values compatible with the recalculation under its assumptions. When an interval excludes zero, it corresponds to an unadjusted two-sided test that rejects a zero mean difference at the associated conventional threshold; it does not account for the fact that multiple secondary outcomes were assessed.

These are unadjusted recalculations from posted group means, standard deviations, and group sizes. They are not replacements for the trial’s analysis. The sponsor’s reported p-values are close to the recalculated values, though not identical for every endpoint. The recalculation uses the posted summary statistics and does not incorporate any unreported covariate adjustment, missing-data procedure, or analysis-population rule. The registry’s own analysis remains the trial’s reported inferential analysis; because no discrepancy flag is recorded, there is no noted reason to give the recalculation precedence over it.

What does variation mean for the estimates?

A standard deviation describes the spread of individual observations around a group mean. It is different from a standard error, which describes the sampling uncertainty in an estimated mean. General statistical reasoning: greater variability can make a mean difference harder to estimate precisely when group sizes are otherwise similar. The TOTPAR summaries include standard deviations, allowing an unadjusted comparison of group means. The primary outcome instead has full ranges but no standard deviations, so the same reconstruction is not available for that endpoint.

Statistical significance is not a measure of clinical importance. The registry does not provide a threshold for a clinically meaningful TOTPAR difference, and the recalculated standardized effect sizes do not establish such a threshold. Readers should distinguish whether a result is statistically distinguishable from zero under a particular model from whether its size matters to patients.

What are the sample-size illustrations?

The planning illustrations use the observed effects, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They show participants per arm for 80% or 90% power when planning for 100%, 75%, or 50% of the observed effect. These are hypothetical planning calculations, not the trial’s original design justification and not observed power. The registry does not report the trial’s sample-size assumptions or justification. Planning from an effect observed in the same trial can also be optimistic if that observed estimate is unusually large; the reduced-effect scenarios illustrate how a smaller assumed effect changes the planning requirement without establishing which effect is correct.

For continuous outcomes, the illustrations use participants per arm. General explanation: equal allocation is a simplifying assumption for these calculations, and actual trial planning may need to account for the intended allocation, outcome variability, missing observations, multiplicity, and the planned analysis. The registry does not report whether these planning considerations were part of the original design. The illustrations should therefore be read as conditional scenarios based on their stated assumptions, not as a retrospective assessment of whether the completed trial was adequately powered.

Why do over-dispersion and model choice matter?

General explanation: over-dispersion occurs when observed variability exceeds what a statistical model expects. A model that assumes too little variation can understate uncertainty and make evidence appear more precise than it is. This concern is relevant to many outcome types, but the registry does not report an over-dispersion assessment for this trial. Nor does it provide enough detail to determine whether a model-based analysis was used for the primary outcome. It would therefore be inappropriate to claim that over-dispersion occurred or affected the findings.

Overall, the posted secondary data permit simple unadjusted comparisons of means and provide a basis for conditional planning illustrations. They do not supply the full protocol, analysis plan, model diagnostics, or missing-data details needed to reproduce every trial analysis. The primary p-value is reported, but the absence of a primary effect estimate and confidence interval limits interpretation of both magnitude and precision.

10. Analyses Reported by the Sponsor

The registry’s own primary analysis reports a two-sided test with p = 0.566. It does not provide a primary treatment-effect estimate or confidence interval alongside that p-value. The recalculated secondary comparisons use the posted group means, standard deviations, and group sizes to estimate unadjusted mean differences and confidence intervals. Those recalculations are distinct from the sponsor’s reported analyses and do not incorporate any unreported adjustment or analysis choices.

For the three posted TOTPAR comparisons, the sponsor’s reported p-values are 0.013, 0.006, and 0.013. The corresponding recalculated unadjusted p-values are 0.013, 0.005, and 0.014. The small differences show that the recalculation is not an exact reproduction of every sponsor-reported test. The registry does not explain the differences, so a cause should not be inferred. The record does not flag a discrepancy requiring the sponsor’s analysis to take precedence over the recalculation; nonetheless, the sponsor’s results are the trial’s own reported tests, while the recalculated estimates are transparent unadjusted analyses of summary statistics.

Neither set of secondary p-values addresses multiplicity, and neither changes the interpretation of the primary result. The primary test does not show a statistically detectable difference under the reported analysis, but its missing effect estimate and confidence interval prevent a direct assessment of magnitude and precision. For all outcomes, the registry does not report enough detail to confirm whether the analyses used the same populations or missing-data rules as the recalculations.

11. Multiplicity, Missing Data and Analysis Populations

The registry reports a primary outcome and lists 25 secondary outcome measures. It does not report a multiplicity-control procedure, such as a strategy for allocating the overall error rate across multiple secondary tests. Without such a strategy, unadjusted secondary p-values should be read as exploratory rather than as a set of independently confirmatory findings. A result below a conventional threshold may be less compelling when considered among many tested outcomes.

The primary outcome is reported as a two-sided test across three listed groups, but the exact contrasts and any adjustment for multiple comparisons are not specified. The registry also does not describe an interim-analysis plan, stopping boundaries, or whether interim looks occurred. Those details are not reported in the registry record and should not be guessed.

The primary population description identifies a modified intent-to-treat population from the first cohort randomized to four treatment arms in a 4:4:1:1 ratio. It does not give a complete operational definition of that population, such as the criteria for inclusion in the analysis or the handling of participants without usable outcome data. The registry’s primary results list group sizes and summary values, but they do not explain how missing observations were treated. For the secondary outcomes, the posted summaries provide group sizes, but the corresponding missing-data rules and analysis-population definitions are not reported.

Missing data can affect an analysis if the probability of having an observed outcome is related to treatment or to the outcome itself. General explanation: complete-case analyses, imputation, and model-based approaches can rely on different assumptions, so knowing the method is important for judging robustness. The registry does not identify which approach was used for each outcome or report sensitivity analyses addressing missingness.

The registry reports no sample-size justification or stated power target for the original trial. The separate planning illustrations are conditional recalculations based on observed secondary effects; they do not resolve the missing design rationale. Collectively, the absent multiplicity, interim-analysis, missing-data, and analysis-population details constrain how fully the registry results can be evaluated.

12. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: calculus urinary (0.5%), monoparesis (0.4%).

The registry separates serious adverse events from other adverse events and reports them by treatment and phase. In the multiple-dose phase, the dexketoprofen-tramadol group has 0 serious adverse events among 270 at risk, and the tramadol group has 1 among 268 at risk. In the single-dose phase, the dexketoprofen-tramadol group has 1 among 211 at risk, the tramadol group has 0 among 207 at risk, and the placebo group has 0 among 119 at risk. The registry records 0 deaths in each listed safety group.

Other adverse events are reported separately: 68 among 270 at risk and 73 among 268 at risk in the two multiple-dose groups; 28 among 211 at risk, 31 among 207 at risk, and 11 among 119 at risk in the listed single-dose groups. The registry lists “Calculus Urinary” at 0.5% and “Monoparesis” at 0.4% among the top serious-event terms. It does not specify in this summary which treatment group each term corresponds to.

These are descriptive counts for groups and phases, not proof that treatment caused or prevented an event. The phase-specific groups should not be combined into an overall participant count, and the different treatment exposure periods matter when comparing the summaries. The registry does not provide event definitions, severity grading beyond the serious-versus-other distinction, exposure-adjusted rates, or detailed causal assessments. Sparse serious-event counts also limit how much can be concluded about comparative safety.

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

The registry’s primary analysis does not show a statistically detectable difference in time to the specified pain-response threshold under the reported test: p = 0.566. That statement concerns the evidence produced by the reported analysis. It is not proof of equivalence, proof that no effect exists, or proof that any possible effect is too small to matter. The registry does not provide the primary contrast estimate or its confidence interval, leaving the magnitude and precision of the primary comparison unclear.

The posted secondary summaries show higher mean total pain relief for the combination than for tramadol during each of the reported single-dose time windows. The unadjusted recalculations and the sponsor’s reported tests support a difference in those summaries under their respective analyses. However, those results are secondary, multiple outcomes are listed, and the registry does not report a multiplicity adjustment. They should be interpreted as supportive or exploratory rather than as a replacement for the primary analysis.

The two endpoint types answer different questions. Time to first threshold achievement concerns the timing of a response meeting a defined criterion. TOTPAR concerns accumulated pain relief over an interval. Different measures can yield different statistical findings without contradiction. The registry’s incomplete information on the primary contrast and analysis details means the relationship between the measures cannot be resolved fully from the posted results.

The safety counts describe events recorded by treatment phase. They do not establish causality, and the available serious-event counts are too limited to support broad comparative safety conclusions. No treatment recommendation follows from these registry summaries. The record provides useful information about trial design and selected outcomes, but it does not report all details needed to judge the clinical importance, robustness, or generalizability of the findings.

14. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation depends on more than a p-value. The primary result is reported as a test without a treatment-effect estimate or confidence interval. Readers can see the group means and full ranges, but those summaries do not quantify the uncertainty around a specific contrast. Reporting an effect estimate with an interval would make the magnitude and precision of the primary finding easier to assess.

It also highlights the importance of matching the statistical method to the outcome and understanding the analysis population. The endpoint is time to first response, while the registry labels the test a t-test and reports means and ranges. The record does not explain how participants who did not meet the threshold, or those with missing assessments, were handled. Such details determine what the estimated mean represents and how the test should be interpreted.

The secondary outcomes demonstrate another general challenge: multiple comparisons. Several posted pain-relief measures point in the same direction, but 25 secondary outcome measures are listed and no multiplicity procedure is reported. A consistent pattern can be informative, yet unadjusted significance across selected secondary outcomes should not be treated as equivalent to a single prespecified primary result.

Finally, the planning illustrations show how sample-size requirements depend on assumptions about the effect to detect. They are not observed power and do not document the design rationale for this completed trial. The registry does not report that rationale, the analysis plan, or key missing-data procedures. For biostatisticians and clinical researchers, the central lesson is to distinguish posted results from unreported methodological details and to keep conclusions proportional to the evidence and its precision.

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.

Several limitations specific to this record constrain interpretation. The primary test is reported across three groups, but the exact treatment contrasts and test specification are not stated. Although the endpoint is described as time to first response, the results are reported as means and full ranges, and the registry does not explain the handling of participants who did not reach the threshold during the observation period. No primary effect estimate or confidence interval is posted.

The population description refers to a modified intent-to-treat analysis from the first cohort randomized to four arms, but does not fully define inclusion in that analysis. The record does not describe missing-data handling, the assessment schedule, or sensitivity analyses. These gaps limit assessment of whether the posted summaries represent all randomized participants or how robust they are to alternative assumptions.

The treatment schedules differ by phase, including groups that began with placebo and switched to active treatment during the multiple-dose phase. The primary endpoint concerns only the first 8 hours, while the intervention descriptions extend through Day 5. Results from the initial period should not be assumed to describe effects across the full treatment period. The primary objective’s relationship to all randomized arms is also not fully detailed.

The secondary results are unadjusted and sit within a record listing 25 secondary outcomes. The registry does not report a multiplicity strategy or clarify which secondary tests were confirmatory. The recalculated mean comparisons use summary statistics and cannot reproduce unreported covariate adjustments or missing-data procedures. Differences between recalculated and sponsor-reported p-values are small but unexplained.

Finally, the registry does not report the sample-size justification, full statistical analysis plan, interim-analysis details, or comprehensive safety assessment methods. These are limitations of the information in the registry record; their absence does not establish that the details were absent from the trial’s internal documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Evaluating Dexketoprofen Trometamol/Tramadol Hydrochloride Analgesic Efficacy in Acute Low Back Pain — NCT05170841.
• Registry record last updated 2025-01-09; status last verified 2024-08.
• Results first posted 2025-01-09.
• 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

NCT05170841 is a completed, randomized, quadruple-masked, parallel-group Phase 4 trial of dexketoprofen trometamol with tramadol for moderate to severe acute pain associated with acute low back pain. The registry reports enrollment of 538 and describes a single-dose phase through 8 hours and a multiple-dose phase through Day 5.

The primary endpoint measures time to first reaching an NRS-PI score below 4 or a pain reduction of at least 30% during the first 8 hours. The registry reports a two-sided test with p = 0.566, but no primary effect estimate or confidence interval. Posted secondary TOTPAR comparisons favor the combination in their mean summaries versus tramadol, with unadjusted recalculations and sponsor tests indicating differences; these findings are secondary and no multiplicity adjustment is reported.

Safety summaries are descriptive and phase-specific. Important analysis details, including missing-data procedures, the full primary contrast specification, and the original sample-size justification, are not reported in the registry record. The available results support cautious interpretation of the posted endpoints, not a definitive conclusion about clinical importance or comparative safety.