A Pilot Study of CelTx(TM) (Apligraf®) in the Treatment of Gingival Recession Requiring Root Coverage: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of CelTx(TM) (Apligraf®) in the Treatment of Gingival Recession Requiring Root Coverage (NCT00679081), a randomized phase 1, phase 2 study. The primary outcome is Overall Rate of Adverse Events (AEs).

2. Clinical Question

The study was designed as a randomized, controlled pilot study of root coverage for gingival recession. Its stated purpose was to evaluate CelTx as an alternative to tissue from the palate. The study description also expresses an expectation that the study would assess safety and potential effects on oral soft tissue regeneration and wound healing. Those expectations are aims, not findings.

The primary outcome listed in the registry is the overall rate of adverse events, measured as participants. The posted counts are separated into CelTx Site, Graft Site, and Other Location. The record does not explain how those location categories map onto randomized participants, whether a participant could contribute to more than one category, or whether they represent treatment arms. This distinction matters: a count for an anatomical or event location is not automatically a comparison of randomized treatment groups.

Periodontal health, aesthetic measures, post-surgical comfort, and subject preference are listed as secondary outcome domains. Results for those domains are not reported in the registry record. The main question that can be addressed from the posted results is therefore limited to the recorded adverse-event counts and their uncertainty, with caution about the relationship between location categories and randomized treatment assignment.

3. Trial Design

This was a prospective, randomized, controlled pilot study with a parallel-group model and no masking. The registry lists the study as phase 1 and phase 2. The condition was gingival recession, and the stated focus was root coverage for Miller Class I or II recession defects in people who desired treatment. The sponsor was Organogenesis.

The registry lists an enrollment of 15 and gives a start date of 2008-05 and a primary completion date of 2010-09. The study status is terminated. The record does not state why the study was terminated, how many participants completed follow-up, or whether enrollment reached the planned target. A termination status alone does not explain the circumstances or the reason for stopping.

The interventions are CelTx and an autologous sub-epithelial connective tissue graft. The posted outcome data list 15.0 participants at risk for each of three categories: CelTx Site, Graft Site, and Other Location. Those entries should not be read as three separate randomized groups. The record does not describe how the location-specific counts relate to the randomized parallel groups, and the Other Location category is not identified as an assigned intervention.

The primary outcome was adverse events over 6 months. The registry says adverse events were collected at every visit throughout that duration. It lists four secondary outcome domains: periodontal health measures, aesthetic measures, post-surgical subject comfort measures, and subject preference measures. The record does not report details of the randomization procedure, allocation concealment, visit schedule, intervention protocol, follow-up completeness, or analysis populations. Information about these design features is therefore not available 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:

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 Overall Rate of Adverse Events (AEs), measured over 6-month.

The primary endpoint is titled Overall Rate of Adverse Events (AEs), measured as participants over a 6-month timeframe. The registry defines an adverse event as any adverse change in a participant’s medical status compared with baseline, regardless of whether the change is related to the study device or a study procedure. An exacerbation in the frequency or severity of a pre-existing condition also meets the definition. Adverse events were collected at every visit during the 6-month duration.

A broad safety endpoint can capture events that occur during a study without presuming that the intervention caused them. It can therefore describe the recorded burden of adverse experiences, while the definition itself does not establish attribution. Whether an event is related to treatment requires a separate assessment; the registry definition explicitly includes events whether or not related to the device or procedure.

The outcome is expressed as participants with an event, rather than as a continuous measurement. The registry’s posted counts are 2.0 at the CelTx Site, 2.0 at the Graft Site, and 8.0 at Other Location, with 15.0 at risk in each category. The record does not clarify whether these are unique participants, whether categories overlap, or how the site categories correspond to the primary endpoint’s wording of an overall rate. The registry does not report additional endpoint definitions or an event-level breakdown for these counts.

7. Results Posted in the Registry

• Graft Site: 13.3% (2/15) versus 13.3% (2/15) on control; risk difference 0.0 percentage points (95% CI -24.3 to 24.3), risk ratio 1.00 (0.16–6.20); unadjusted two-proportion z-test p = 1.000.
• Other Location: 53.3% (8/15) versus 13.3% (2/15) on control; risk difference 40.0 percentage points (95% CI 9.4 to 70.6), risk ratio 4.00 (1.01–15.81); unadjusted two-proportion z-test p = 0.020.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either has an adverse event recorded for the category under consideration or does not. The registry describes the outcome as participants with an event and reports counts rather than a continuous score. For this kind of data, a risk is the proportion of participants in a group who experience the event. A risk difference expresses the difference between two such risks. A value of zero indicates no observed difference in the compared risks, while positive and negative values indicate direction according to the order of the comparison.

What do the comparison results describe?

The posted comparisons use CelTx Site as the reference category and compare it with Graft Site and Other Location. For Graft Site, the posted risk difference is 0.0, with an unadjusted p-value of 1.0. For Other Location, the posted risk difference is 0.4, with an unadjusted p-value of 0.02. These are comparisons of the categories named in the registry results. Since the record does not state that Other Location is a randomized arm, this comparison should not be interpreted as a randomized treatment contrast. Nor does the registry explain whether the site categories are mutually exclusive or how many distinct participants contributed to each.

A p-value is a measure calculated under a statistical model. In general, it describes how unusual data at least as incompatible with a null hypothesis would be if that null model and its assumptions held. It is not a measure of the probability that the null hypothesis is true, nor does it state the probability that the observed finding will recur. The posted p-values are labeled unadjusted. The registry does not report the test used, the model details, or any adjustment for multiple comparisons.

Why is uncertainty important with event counts?

Event counts of this size can produce imprecise estimates. A small change in the number of participants with an event can materially change the estimated risk, so a point estimate alone does not communicate how much uncertainty remains. Confidence intervals describe a range of estimates compatible with the observed data under a particular method and confidence level. The registry posts intervals for the risk differences, but the confidence level and interval calculation method are not reported in the registry record. The interval for CelTx Site versus Graft Site includes zero, while the interval for CelTx Site versus Other Location lies above zero. These intervals do not resolve the underlying uncertainty about the category definitions or participant overlap.

The registry also reports risk ratios and odds ratios for the comparisons. These are relative measures: a risk ratio compares risks, while an odds ratio compares odds. Relative measures can be difficult to interpret when counts are small, and their meaning depends on the comparison groups being well defined. The posted risk ratio and odds ratio for Graft Site versus CelTx Site are 1.0 and 1.0, respectively; for Other Location versus CelTx Site, they are 4.0 and 7.429. These measures do not make Other Location a treatment arm, and they should not be treated as causal estimates without a clear design-based comparison.

How should the planning illustrations be read?

The registry includes sample-size planning illustrations for the CelTx Site versus Other Location comparison. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. Under those assumptions, planning for 100% of the observed effect gives 21 participants per arm for 80% power and 28 participants per arm for 90% power. Planning for 75% of the observed effect gives 35 participants per arm for 80% power and 46 participants per arm for 90% power. Planning for 50% of the observed effect gives 70 participants per arm for 80% power and 92 participants per arm for 90% power.

These are planning illustrations derived from the observed comparison, not the trial’s original design justification and not observed power. The comparison involves Other Location, whose relationship to random assignment is not explained, so the illustrations should not be treated as a sound basis for planning a randomized treatment comparison without further information. The registry does not report the trial’s own sample-size justification, target difference, or statistical analysis plan.

For binary outcomes, over-dispersion is not the usual concern in the way it is for count outcomes modeled with a Poisson distribution. More broadly, any model that assumes more regular variation than the data contain can understate uncertainty. With sparse event counts, the choice of statistical method can affect estimates and intervals. The registry does not report enough analysis detail to evaluate those choices or independently assess model assumptions.

Finally, statistical evidence must be interpreted alongside the design and data structure. Randomization can support causal comparisons when outcomes are analyzed according to well-defined assigned groups and follow-up is adequately described. Here, the posted safety counts are organized by site, and their mapping to randomized groups is not given. The comparison statistics therefore describe the posted categories; they do not by themselves establish a treatment effect.

10. Confidence Intervals and Precision

The risk-difference interval for CelTx Site versus Graft Site includes zero. The point estimate is 0.0, and the interval extends in both directions around that estimate. This is compatible with no observed difference, but it also allows differences in either direction. The interval is broad relative to the point estimate, reflecting that the event counts provide limited precision. The result should not be read as proof of equivalence or as evidence that meaningful differences have been ruled out.

For CelTx Site versus Other Location, the estimated risk difference is 0.4 and the posted interval lies above zero. The interval indicates uncertainty around the estimated difference, but it concerns the named site categories. Because the registry does not establish that Other Location is a randomized treatment group, the interval cannot be interpreted as uncertainty around a randomized comparison of CelTx with the graft.

A confidence interval is generally a range produced by a statistical method to represent uncertainty in an estimate. Its interpretation depends on the method and confidence level. The registry record does not report the confidence level or the calculation method for these intervals. Exact interval limits are therefore not repeated in this explanation. The unadjusted p-values add information about compatibility with a null model, but they do not replace the intervals or explain the precision of the underlying estimate.

The 15.0 participants at risk listed for each category, together with the small event counts, limit precision. The record does not provide enough information about missing observations, follow-up completion, or overlap between categories to assess whether the displayed denominators represent the same complete set of people. More precise estimates would require clear group definitions and outcome data with adequate follow-up; the posted results do not establish how much further information would be needed for a particular research question.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four secondary outcome domains: periodontal health measures, aesthetic measures, post-surgical subject comfort measures, and subject preference measures. It reports four secondary outcomes posted, but no secondary analysis results are listed. The record also lists five outcome measures and zero analyses. The registry does not describe a multiplicity strategy, such as prioritizing outcomes or adjusting interpretation for testing several outcomes. The reported unadjusted p-values should therefore be understood as unadjusted; the record does not indicate whether any broader family of comparisons was planned.

Missing-data methods are not reported in the registry record. There is no description of how missing visits, incomplete follow-up, withdrawals, or unavailable outcome measurements were handled. The record does not report participant flow or the number included in an analysis population. Although the primary outcome description says adverse events were collected at every visit throughout the 6-month duration, that statement does not establish that all participants attended every visit or that every event was captured.

The analysis populations are also not reported in the registry record. There is no statement specifying whether results were based on all randomized participants, participants who received an intervention, or another group. The site-specific denominators are each 15.0, but the record does not explain how those denominators relate to the randomized groups or whether the same participants appear in multiple site categories.

These omissions limit assessment of potential bias and the statistical interpretation of the comparisons. Without a clear account of follow-up, analysis populations, missing data, and outcome multiplicity, it is not possible to determine whether the posted results reflect the original analysis plan or how robust they are to alternative analytic choices.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event information lists zero participants affected in each category: CelTx Site, Graft Site, and Other Location. Each category has 15 at risk. No serious-event terms are listed. The death count is not reported in the registry record; a missing count should not be read as a reported zero.

For other adverse events, the registry lists 2.0 participants affected at CelTx Site, 2.0 at Graft Site, and 8.0 at Other Location, with 15.0 at risk in each category. These are counts for the named locations. The record does not say whether the categories overlap or identify the events included in each count. It therefore does not establish that the counts represent separate groups of participants or events attributable to particular interventions.

Zero serious events recorded in these small categories means that none were posted for the listed groups; it does not establish that serious events could not occur or that the risk is zero. The registry record does not provide further serious-event details, event-level descriptions, or a treatment-relatedness breakdown. The broad adverse-event definition includes changes whether or not related to a device or procedure, so these counts should not be treated as evidence of causation.

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

The posted safety results describe equal counts of 2.0 participants with an adverse event at CelTx Site and Graft Site, each with 15.0 at risk. The corresponding posted risk difference is 0.0, with an unadjusted p-value of 1.0. This is a descriptive finding for the categories as recorded. The available information does not establish that these categories correspond directly to randomized treatment groups, and an equal observed count is not evidence that the interventions are equivalent.

The Other Location category has 8.0 participants with an adverse event among 15.0 at risk. Its posted comparison with CelTx Site has a risk difference of 0.4 and an unadjusted p-value of 0.02. The statistical contrast is between location categories; it does not show that CelTx differs from the graft in adverse-event risk. The registry does not explain what Other Location represents, whether participants can appear in more than one category, or how these counts relate to assigned treatment.

The study set out to evaluate CelTx as an alternative to palatal tissue in root coverage and listed adverse events as its primary outcome. The posted safety counts do not establish whether any event was caused by treatment, and the registry does not report results for the secondary outcome domains. No conclusion about periodontal health, aesthetics, comfort, or participant preference can be drawn from the outcome names alone.

The results also do not establish the absence of uncommon or serious harms. Zero serious adverse events were posted for each category, but the denominators are limited and the death count is not reported. The record’s terminated status and lack of analysis details add uncertainty about study completion and interpretation. These observations are best read as a limited account of recorded events, not as a definitive estimate of comparative safety or overall treatment performance.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates how outcome labels and data structure shape the meaning of an estimate. A randomized, parallel-group design can support comparisons between assigned interventions, but the posted safety results are organized by CelTx Site, Graft Site, and Other Location. Without an explanation linking those categories to randomization, the comparisons cannot simply be presented as treatment effects. Clear definitions of groups and denominators are essential before interpreting a risk difference, ratio, or p-value.

The event counts are small, so point estimates have substantial uncertainty. The CelTx Site and Graft Site categories have the same posted count, but their comparison interval includes differences in either direction. This is a useful reminder that a non-difference in observed counts is not the same as evidence that two interventions have equal effects. Precision and the range of plausible effects matter alongside the point estimate.

The Other Location comparison also shows why statistical significance cannot be separated from study design. Its unadjusted p-value is 0.02, but that value concerns a location category whose role is not explained, rather than a clearly defined randomized comparator. A small p-value cannot repair ambiguity in the comparison or establish causation.

Finally, planning illustrations based on an observed effect are sensitive to how that effect was obtained. The registry identifies the assumptions behind these illustrations, but the record does not report an original sample-size justification or analysis plan. This makes the study useful for discussing the limits of inference from small pilot data, while leaving key questions about design, analysis, and generalizability unresolved.

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 principal limitation is uncertainty about the relationship between randomized treatment assignment and the posted site categories. Although the study is described as randomized and parallel, the primary safety counts are listed for CelTx Site, Graft Site, and Other Location, each with 15.0 at risk. The registry does not clarify whether each category is a randomized arm, a site within participants, or another classification. Other Location is not described as an intervention. This makes a treatment-effect interpretation of the posted comparisons uncertain.

The record does not explain whether the location categories overlap or whether counts represent unique participants. It also does not provide event-level descriptions or a breakdown of whether events were considered related to treatment. Because the endpoint definition includes events whether or not related to the device or a procedure, the counts alone cannot establish attribution.

The study enrolled 15 participants, and the event counts are small. The resulting estimates have limited precision, particularly for outcomes that may be uncommon. The registry does not report participant flow, completion of follow-up, missing-data handling, analysis populations, the randomization method, or allocation concealment. It does not state why the study was terminated. These gaps prevent a full assessment of selection, attrition, and analysis-related bias.

The registry lists secondary outcome domains but does not report their analysis results. It also does not report a multiplicity plan, statistical analysis plan, or the trial’s own sample-size justification. The planning illustrations use the observed CelTx Site versus Other Location effect, which is not clearly a randomized treatment contrast. These limitations mean the posted findings should be treated as descriptive and preliminary rather than as definitive comparative evidence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pilot Study of CelTx(TM) (Apligraf®) in the Treatment of Gingival Recession Requiring Root Coverage — NCT00679081.
• Registry record last updated 2012-01-11; status last verified 2012-01.
• Results first posted 2011-11-21.
• 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

NCT00679081 is a prospective, randomized, controlled pilot study of CelTx and autologous sub-epithelial connective tissue grafting for gingival recession requiring root coverage. The registry lists a parallel design with no masking, phase 1 and phase 2, enrollment of 15, and status terminated. The start date is 2008-05 and primary completion is listed as 2010-09.

The primary outcome is the overall rate of adverse events during 6 months. The posted counts are 2.0 at CelTx Site, 2.0 at Graft Site, and 8.0 at Other Location, with 15.0 at risk in each category. Serious adverse events are listed as zero in each category; no serious-event terms are listed, and deaths are not reported. The record does not explain how site categories correspond to randomized groups.

Four secondary outcome domains are listed, but their results are not reported in the registry record. Details on missing data, analysis populations, the statistical analysis plan, and the trial’s sample-size justification are also not reported. The posted counts and comparisons therefore support a limited descriptive reading, with uncertainty about group definitions and comparative interpretation.