Clinical Studies
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Statistical Report
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Study description
| Study design: | |
| Number of centers: | 1 |
| Blinding: | Double blind |
| Randomization: | Block randomization |
| Name of medical device: | BioStick (BS) ™ |
| Comparator: | BioStick (BS) with low light |
This study compares the efficacy of Syrolight BioStick device with active light to control with low light density
Objectives:
The primary objectives of this study are to:
- Compare time to healing between the active device and the placebo control
The secondary objectives of this study are to:
- Compare the reduction in pain, ability to speak eat and drink between the active and placebo treatment.
- Evaluate patients’ satisfactory of the products.
Randomization
Block randomization
Study endpoints
Primary endpoint:
Efficacy:
Compare the time to cure in days
Compare the response grade for each group.
Secondary endpoints:
Safety:
Evaluation of adverse events.
Sample size
Forty (40) subjects partitioned into 2 groups.
Twenty allocated randomly to receive active treatment and 20 allocated to receive control treatment.
The primary end point of this study is time to cure (number of days to obtain total cure). The expected difference between the active and placebo groups is anticipated to be at least two days (with standard deviation of two).
A total of 40 enrolled patients (20 in each group) will provide 80% power at a 5% significance level and 95% Confidence Interval of Difference taking into account a 15% drop out rate.
Analysis set
The full analysis set including all enrolled subjects in the study (ITT) was the primary analysis set.
Due to one subject that was lost to follow-up and one subject that used additional medications during treatment the modified ITT served as the primary analysis set.
Analysis method
Data was analyzed using the SPSS software (version 17.00, SPSS Inc.).
Baseline characteristics are presented as descriptive statistics (frequency (%) or mean, standard deviation (SD), standard error (SE) minimum, median and maximum).
Comparison between treatment arms of time to cure, number of treatments and lesion size is based on independent t-test.
Comparison of grade at baseline level is based on Mann Whitney test.
Safety is assessed descriptively.
Significance level was defined as a=0.05.
Missing data
No imputation for missing values was applied.
Forty subjects with Aphthous Stomatitis participated in double blind placebo control study to evaluate the efficacy of BioStick (BO) phototherapeutic device in the treatment of Aphthous Stomatitis.
Compliance: 90% of placebo group and 100% of treated group complied with the study.
Demographic characteristics:
No significant differences between groups.
All subjects are Caucasian, the majority male, age of 36.8 ±11.9.
Baseline characteristics:
Subjects suffer from 1 to 3 lesions. The average lesion size of the placebo group was significantly smaller than in the treated group 13.56± 9.3 vs. 21.80±12.88, meaning that the treated group started the study in inferior condition.
The majority of both groups suffer from sever pain, burning sensation, speech and eating difficulties.
Most of the lesions were located in the lower lip.
Efficacy:
All subjects archived complete cure, as noted as complete recovery in all measurements and size of lesion equal to 0.
There are significant differences in the days to total cure, the treat group had significantly shorter time to cure than the placebo group (3.95±2.82 compared to 5.89±2.95, p=0.046)
There are significant differences in the number of treatments used until total cure, the treat group had significantly less treatments than the placebo group (12.56±7.30 compared to 20.00±8.94, p=0.010).
Subjective evaluation of efficacy
In the treated group the majority (60% to 73.3%) stated good to total cure in all measurements (pain, burning sensations, eating & speech difficulties) compared to approximately 29% to 35% in the placebo group.
Continence of use
80% of subjects from treated group grade the device better to much better that comparative treatments while only 16.7% from placebo group grade the device as much better.
The majority of both groups would like to use the device again (above 80%)
86.7% of the subjects in the treated group would like to buy the device compared to only 60% of subjects in the placebo group.
Safety:
No adverse events were recorded.
Tables:
Table 14.1.1: Study dates
| Placebo | Treat | |
| N | 18 | 20 |
| Date first subject screened | 05.7.2007 | 13.6.2007 |
| Date last subject - screened | 31.5.2009 | 05.6.2009 |
| Date last subject – Final visit | 03.6.2009 | 14.6.2009 |
Table 14.1.3: Demographic characteristics
| Placebo | Treat | P value | ||||
| N | % | N | % | |||
| Gender | Male | 11 | 61.1% | 11 | 55.0% | 0.752* |
| Female | 7 | 38.9% | 9 | 45.0% | ||
| Race | Caucasian | 18 | 100.0% | 20 | 100.0% | 1.000* |
| Age (years) | N | 18 | 20 | 0.713** | ||
| Mean | 36.0 | 37.5 | ||||
| Median | 30.0 | 38.0 | ||||
| SD | 12.8 | 11.3 | ||||
| Minimum | 21.0 | 20.0 | ||||
| Maximum | 61.0 | 56.0 | ||||
The majority in both groups are women, all from Caucasian origin.
The average age was 36 for placebo group and 37.5 for treated group.
No significant differences in the demographic characteristics.
Table 14.1.4: Aphthous stomatitis condition at baseline
| Placebo | Treat | P value | ||||
| N | 18 | 20 | 0.601 | |||
| Time from diagnosis ( Days) |
Mean | 1.39 | 1.20 | |||
| Median | 1.00 | 1.00 | ||||
| SD | .61 | .70 | ||||
| Minimum | .00 | .00 | ||||
| Maximum | 2.00 | 2.00 | ||||
| Suffered in the past | N % | 15 | 83.3% | 19 | 95.0% | 0.328 |
| Treated in the past | N % | 13 | 72.2% | 14 | 70.0% | 1.000 |
Days from diagnosis: 50% of subject arrived to the clinic within 1 day.
The majority suffered in the past (above 83%) and 70% of both groups were treated in the past.
Table 14.1.4.1: Past Medication
No past medication recoded
Table 14.1.5: Enrollment status
Table 14.1.5.1: Number of lesions:
| Number of lesions | Placebo | Treat | P value | ||
| N | % | N | % | ||
| One lesion | 13 | 72.2% | 14 | 70.0% | 0.979 |
| Two lesions | 4 | 22.2% | 5 | 25.0% | |
| Three lesions | 1 | 5.6% | 1 | 5.0% | |
The majority of subjects in both groups (70%) had one lesion.
Table 14.1.5.2: Location of lesions:
| Lesion 1 | Lesion2 | Lesion 3 | ||||||||||
| Placebo | Treat | Placebo | Treat | Placebo | Treat | |||||||
| N | % | N | % | N | % | N | % | N | % | N | % | |
| 1 Gingival Mucosa | 3 | 16.7 | 6 | 30.0 | 3 | 50.0 | 2 | 33.3 | ||||
| 2 Tongue | 6 | 33.3 | 2 | 10.0 | 1 | 16.7 | 2 | 33.3 | ||||
| 3 Upper Lip | 1 | 5.6 | 1 | 5.0 | 1 | 16.7 | 1 | 16.7 | ||||
| 4 Lower Lip | 7 | 38.9 | 8 | 40.0 | 1 | 16.7 | 1 | 16.7 | 1 | 100% | ||
| 5 Hard palate | 1 | 5.6 | ||||||||||
| 6 Soft palate | 3 | 15.0 | 1 | 100% | ||||||||
| Total | 18 | 100.0 | 20 | 100.0 | ||||||||
The majority of lesions are in the lower lip for both groups.
Table 14.1.5.3: Size of lesions (mm2):
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Lesion 1: at baseline there are significant differences in the first lesion size, the treatment group has significantly bigger lesions compared to the placebo 21.80 mm2 vs. 13.56 mm2 respectively (p=0.031)
Lesion 2: same trend but not statistically significant.
Table 14.1.5.4: Condition of lesion at baseline
| Placebo | Treat | P value | ||||
| N | % | N | % | |||
| Pain | None | 1 | 5.6% | 0 | .0% | 0.806 |
| Moderate | 5 | 27.8% | 6 | 30.0% | ||
| Severe | 12 | 66.7% | 14 | 70.0% | ||
| Burning Sensation | None | 1 | 5.6% | 1 | 5.0% | 0.874 |
| Mild | 2 | 11.1% | 0 | .0% | ||
| Moderate | 4 | 22.2% | 7 | 35.0% | ||
| Severe | 11 | 61.1% | 12 | 60.0% | ||
| Speech Difficulties | None | 3 | 16.7% | 2 | 10.0% | 0.613 |
| Mild | 1 | 5.6% | 2 | 10.0% | ||
| Moderate | 5 | 27.8% | 4 | 20.0% | ||
| Severe | 9 | 50.0% | 12 | 60.0% | ||
| Eating Drinking Difficulties | None | 1 | 5.6% | 0 | .0% | 0.919 |
| Mild | 0 | .0% | 1 | 5.0% | ||
| Moderate | 3 | 16.7% | 4 | 20.0% | ||
| Severe | 14 | 77.8% | 15 | 75.0% | ||
The majority of both groups suffer from sever pain, burning sensation, speech and eating difficulties.
Table 14.1.6: Medical History
| Placebo | Treat | P value | ||||
| N | % | N | % | |||
| Number of subjects | 3 | 16.67% | 0 | 0% | ||
| Description of findings | ||||||
| Hypercholesterolemia + hypertension | 1 | 5.6% | 0 | 0% | ||
| Hypothyroidism | 1 | 5.6% | 0 | 0% | ||
| Penicillin allergy | 1 | 5.6% | 0 | 0% | ||
Three subjects from the placebo group had some non related medical history.
Table 14.1.7: Medication History
No Medications were stopped within the last 14 days.
Table 14.1.8: Subject validity status for analysis
| Placebo | Treat | |||
| N | % | N | % | |
| Number of subjects | 20 | 100% | 20 | 100% |
| Complete study | 18 | 90% | 20 | 100% |
| Reasons for incomplete | ||||
| Lost to Follow up | 1 | 5.0% | ||
| Protocol violation use of other medication | 1 | 5.0% | ||
There were two subjects that didn’t complete the study, both from the Placebo group.
Table 14.2.1: Time to total cure
| Treatment | *P value | |||
| Placebo | Treat | |||
| Days To Total Cure | N | 18 | 20 | 0.046 |
| Mean | 5.89 | 3.95 | ||
| Median | 5.50 | 3.00 | ||
| SD | 2.95 | 2.82 | ||
| Minimum | 2.00 | 1.00 | ||
| Maximum | 12.00 | 10.00 | ||
| Number of treatments during period | N | 18 | 18 | 0.010 |
| Mean | 20.00 | 12.56 | ||
| Median | 19.50 | 9.50 | ||
| SD | 8.94 | 7.30 | ||
| Minimum | 7.00 | 5.00 | ||
| Maximum | 39.00 | 30.00 | ||
| Total days in treatment | N | 18 | 20 | 0.041 |
| Mean | 6.89 | 4.90 | ||
| Median | 6.50 | 4.00 | ||
| SD | 2.95 | 2.83 | ||
| Minimum | 3.00 | 2.00 | ||
| Maximum | 13.00 | 11.00 | ||
| Rate of use (number of treatments/days) | N | 18 | 18 | 0.724 |
| Mean | 2.87 | 2.84 | ||
| Median | 3.00 | 3.00 | ||
| SD | .23 | .28 | ||
| Minimum | 2.33 | 2.00 | ||
| Maximum | 3.00 | 3.00 | ||
*p value based on independent t-test
There are significant differences in the days to total cure, the treat group had significantly shorter time to cure than the placebo group (3.95±2.82 compared to 5.89±2.95, p=0.046)
There are significant differences in the number of treatments used until total cure, the treat group had significantly less treatments than the placebo group (12.56±7.30 compared to 20.00±8.94, p=0.010)
There are no significant differences between groups in the rate of use (2.84±0.28 compared to 2.87±0.23, p=0.724)
Fig 1: Number of days to total cure
Fig 2: Number of treatments until total cure
Table 14.2.2: Improvement in lesion condition at the end of follow up
| Placebo | Treat | |||
| N | % | N | % | |
| Number of subjects | 20 | 100% | 20 | 100% |
| Complete study | 18 | 90% | 20 | 100% |
| Complete recovery | ||||
| Pain | 18 | 100% | 20 | 100% |
| Burning sensation | 18 | 100% | 20 | 100% |
| Speech difficulty | 18 | 100% | 20 | 100% |
| Eating/Drinking difficulty | 18 | 100% | 20 | 100% |
| General status of lesions | 18 | 100% | 20 | 100% |
All subjects in both groups demonstrated complete recovery
Table 14.2.3: Lesion size at end of follow-up
| Treatment | |||
| Placebo | Treat | ||
| Lesion 1 Size (mm2) | N | 18 | 20 |
| Mean | 0 | 0 | |
| Median | 0 | 0 | |
| SD | 0 | 0 | |
| Minimum | 0 | 0 | |
| Maximum | 0 | 0 | |
| Lesion 2 Size (mm2) | N | 6 | 6 |
| Mean | 0 | 0 | |
| Median | 0 | 0 | |
| SD | 0 | 0 | |
| Minimum | 0 | 0 | |
| Maximum | 0 | 0 | |
| Lesion 3 Size (mm2) | N | 1 | 1 |
| Mean | 0 | 0 | |
| Median | 0 | 0 | |
| SD | . | . | |
| Minimum | 0 | 0 | |
| Maximum | 0 | 0 | |
All subjects in both groups demonstrated no lesions at the end of follow-up, therefore size equal to 0.
Table 14.3.1: Time to total cure by home diary
| Placebo | Treat | P value | ||
| Days to Cure Diary | N | 14 | 14 | 0.046 |
| Mean | 5.86 | 3.64 | ||
| Median | 5.50 | 2.00 | ||
| SD | 2.82 | 2.76 | ||
| Minimum | 2.00 | 1.00 | ||
| Maximum | 12.00 | 9.00 |
Table 14.3.2: Stage of cure after two days of treatments
| Total | Worse | No change | Mild | Moderate | Good | Total cure | Good to total cure |
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| Placebo | Pain | 17 | 2 | 11.8% | 7 | 41.2% | 1 | 5.9% | 2 | 11.8% | 3 | 17.6% | 2 | 11.8% | 5 | 29.4% |
| Burning sensation | 17 | 2 | 11.8% | 5 | 29.4% | 4 | 23.5% | 1 | 5.9% | 3 | 17.6% | 2 | 11.8% | 5 | 29.4% | |
| Speech difficulty | 17 | 2 | 11.8% | 4 | 23.5% | 4 | 23.5% | 1 | 5.9% | 4 | 23.5% | 2 | 11.8% | 6 | 35.3% | |
| Eating/Drinking difficulty | 17 | 2 | 11.8% | 5 | 29.4% | 3 | 17.6% | 1 | 5.9% | 4 | 23.5% | 2 | 11.8% | 6 | 35.3% | |
| Treat | Pain | 15 | 0 | 0.0% | 1 | 6.7% | 3 | 20.0% | 2 | 13.3% | 2 | 13.3% | 7 | 46.7% | 9 | 60.0% |
| Burning sensation | 15 | 1 | 6.7% | 1 | 6.7% | 3 | 20.0% | 1 | 6.7% | 2 | 13.3% | 7 | 46.7% | 9 | 60.0% | |
| Speech difficulty | 15 | 1 | 6.7% | 0 | 0.0% | 2 | 13.3% | 3 | 20.0% | 2 | 13.3% | 7 | 46.7% | 9 | 60.0% | |
| Eating/Drinking difficulty | 15 | 0 | 0.0% | 1 | 6.7% | 0 | 0.0% | 3 | 20.0% | 2 | 13.3% | 9 | 60.0% | 11 | 73.3% | |
In the treated group the majority (60% to 73.3%) stated good to total cure in all measurements compared to approximately 29% to 35% in the placebo group.
Fig2: Stage of cure after two days of treatments
Table 14.4.1: Previous treatments
| Placebo | Treat | Total | P value | |||
| N | % | N | % | N | ||
| Number of subjects | 17 | 100% | 16 | 100% | 33 | |
| Used previous treatments | 12 | 70.6% | 10 | 62.5% | 22 | 0.721 |
| Aphtagon | 6 | 50.0% | 2 | 20.0% | ||
| Kanka | 1 | 8.3% | 5 | 50.0% | ||
| Oracorte | 3 | 25.0% | 3 | 30.0% | ||
| Other | 4 | 33.3% | 3 | 30.0% | ||
The majority of the placebo group used Aphtagon in the past,
The majority of the treat group used Kanka in the past.
Table 14.4.2: Comparing the device to previous treatments
| Placebo | Treat | Total | P value | |||
| N | % | N | % | N | ||
| Number of subjects | 14 | 100% | 11 | 100% | 24 | |
| Used previous treatments | 12 | 70.6% | 10 | 62.5% | 22 | 0.721 |
| Grade effectiveness of device | 0.314 | |||||
| Less effective | 2 | 16.7% | 2 | 20.0% | ||
| Similar | 3 | 25.0% | 0 | .0% | ||
| Better | 5 | 41.7% | 4 | 40.0% | ||
| Much better | 2 | 16.7% | 4 | 40.0% | ||
80% of subjects from treated group grade the device better to much better that comparative treatments.
Only 16.7% from placebo group grade the device as much better,
Table 14.4.3: Comfort of use
| Placebo | Treat | |||
| N | % | N | % | |
| Comfort for use | 14 | 100.0% | 13 | 100.0% |
| Comments | ||||
| Comfortable | 8 | 8 | ||
| Complicated to clean after each use | 1 | |||
| Comfortable but not effective | 1 | 1 | ||
| If it was smaller it wouldl be better | 1 | |||
| Depends on location | 1 | |||
| Too long | 1 | |||
| Not greasy or sandy fill in mouth | 1 | |||
Table 14.4.4: Side Effects
| Placebo | Treat | |||
| N | % | N | % | |
| No side effects | 16 | 100.0% | 16 | 100.0% |
No side effects were recorded
Table 14.4.5: Prefer to use the device again on the occurrence of aphta
| Placebo | Treat | |||
| N | % | N | % | |
| Use again | 12 | 80.0% | 13 | 86.7% |
The majority of both groups would like to use the device again (above 80%)
Table 14.4.6: Will you buy the device if exist in the market
| Placebo | Treat | |||
| N | % | N | % | |
| Buy the device | 9 | 60.0% | 13 | 86.7% |
86.7% of the subjects in the treated group would like to buy the device compared to only 60% of subjects in the placebo group.
Table 14.5.1: Concomitant medications
| Group | ID | Drug Name | Units | Daily Dose | Route | Start date | Ongoing | Indication | Related AE |
| Placebo | 3 | elthroxin | mg | 100 | PO | 01.1.2002 | Yes | hypothyroidism | No |
| Placebo | 21 | t.simvastatin | mg | 40 | PO | 01.4.2007 | Yes | hypercholesterolemia | No |
No adverse events were recorded.
Table 14.5.3: Reasons for study termination
| Placebo | Treat | |||
| N | % | N | % | |
| Number of subjects N | 20 | 100 | 20 | 100 |
| Study completed | ||||
| Yes | 18 | 90 | 20 | 100 |
| No | 2 | 10% | 0 | 0 |
| Reasons for premature termination | ||||
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1 | 5 | 0 | 0 |
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1 | 5 | 0 | 0 |
