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Annali di Stomatologia | 2026; 17(2): 268-280 ISSN 1971-1441 | DOI: 10.59987/ads/2026.2.268-280 Articles |
Effectiveness of a mouthwash formulation for minor oral ulcers: a triple-blind randomized controlled trial
Article History
Received: May 23, 2026
Accepted: June 24, 2026
Published: June 30, 2026
Abstract
The present investigation aimed to evaluate the clinical effectiveness and safety of a dedicated mouthwash formulation for the treatment of minor oral ulcers. A 2-week, double-arm, triple-blind, placebo-controlled randomized controlled trial was designed, consisting of two mouthwashes: Group Test (test formulation) and Group Control (placebo). The clinical efficacy has been assessed using the following scores and clinical parameters: pain intensity, measured using the VAS, Ulcer Severity Score (USS) — recording of the surface temperature of the mucous membranes by Infrared Thermography. The main clinical outcomes considered were ulcer count, lesion size, lesion disease duration, disease-free period, perceived pain, and residual scarring. A significant difference in pain level and USS score was detected in favor of the test group compared with the control group (p<0.05). No differences have been detected considering the temperature changes at 7 days and 2 weeks follow-up. The findings suggest that the treatment can produce a significant decrease in oral ulceration pain and symptoms and is useful in improving the clinical course of oral ulcers.
Keywords: oral ulcers; periodontium; recurrent aphthous stomatitis.
1. Introduction
Recurrent aphthous stomatitis (RAS) is a common inflammatory disorder of the oral mucosa with a multifactorial and immune-mediated etiology. Clinically, it is characterized by the recurrent appearance of painful ulcerations affecting the non-keratinized soft tissues of the oral cavity [1–2]. Oral aphthous ulcers are characterized by painful lesions that may be associated with several local and systemic conditions and can significantly impair oral function, including speech, mastication, and oral hygiene [1–2]. Recurrent aphthous stomatitis is the most prevalent ulcerative condition of the oral cavity, with the highest incidence reported in individuals aged 20–30 years [3–4]. Several epidemiological studies have shown a higher prevalence in developed countries and a higher frequency among female subjects than among males. The clinical course is typically characterized by periods of remission alternating with phases of recurrence, with a tendency toward reduced frequency and severity in later adulthood [5–6]. In predisposed individuals, RAS may persist into adulthood and be associated with systemic diseases or immunodeficiency states [2,5,7]. Recent evidence suggests an immunological background involving increased expression of inflammatory mediators. Altay et al. reported elevated salivary levels of irisin, interleukin-2 (IL-2), and interferon-γ (IFN-γ) in patients affected by RAS compared with smoker and non-smoker controls [8]. These findings support the hypothesis that irisin may interfere with soft-tissue healing, potentially serving as a biomarker for disease susceptibility [8]. Although the clinical manifestations of RAS are benign, severe cases may exhibit prolonged healing times exceeding three weeks and a high rate of recurrence. In the presence of persistent or atypical lesions, a biopsy is recommended to exclude alternative etiologies, including malignant disease [9].
Several predisposing factors have been associated with RAS, including genetic susceptibility, hypersensitivity reactions, microbial factors, local trauma, hormonal and immunological imbalances, psychological stress, and smoking habits. In addition, RAS has been linked to nutritional deficiencies (iron, zinc, folic acid, and vitamins B1, B2, B6, and B12), as well as to gastrointestinal disorders such as celiac disease and inflammatory bowel disease [4–5,10–11]. Associations with Behçet’s syndrome, Reiter’s disease, AIDS, neutropenia, and the use of certain medications (e.g., beta-blockers, bisphosphonates, NSAIDs, protease inhibitors, and sulfonamides) have also been reported. In addition, neutropenia and the use of beta-blockers, bisphosphonates, NSAIDs, protease inhibitors, and sulfonamides have been associated with RAS [4–5,10–11]. Various therapeutic approaches have been proposed for the management of RAS, primarily aimed at symptom control rather than disease eradication. However, many patients experience frequent recurrences or refractoriness to both pharmacological and non-pharmacological treatments. Among the factors contributing to treatment failure, the dilution and wash-out effect of saliva and the limited bioadhesion of topical agents to ulcerated mucosal surfaces play a crucial role [5–6,14–17]. Therefore, the development of bioadhesive formulations capable of protecting the ulcer surface and prolonging contact time may represent a promising therapeutic strategy for reducing ulcer recurrence [6,10–13]. The present study aimed to evaluate the clinical efficacy and safety of a novel film-forming mouthwash formulation for the treatment of minor oral ulcers over a 14-day treatment period. The null hypothesis was that no differences would be observed between the test and placebo groups in terms of clinical course and symptom severity of minor oral mucosal ulcers.
2. Materials and Methods
2.1. Ethical Statements
The study was conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice (GCP) guidelines. Written informed consent was obtained from all participating subjects. The protocol was approved by the Territorial Ethics Committee of the Abruzzi Region, Italy (Prot. n. RA/0362820, 05/09/2023). The clinical trial was registered at clinicaltrials. gov (NCT07121361). The study was carried out at the Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara.
2.2. Study Design
This was a single-center, randomized, triple-blind, placebo-controlled clinical trial with a total follow-up of 14 days. (Fig. 2) Participants attended three visits:
- V1 – Baseline: eligibility screening, medical history, baseline measurements, and first supervised administration of the mouthwash.
- V2 – Day 7 (Week 1): clinical evaluation and data recording.
- V3 – Day 14 (Week 2): final evaluation and end of study.
A total of 60 subjects meeting the inclusion criteria were enrolled and randomly allocated in a 1:1 ratio to Group I (Placebo) and Group II (Test formulation). Randomization was computer-generated. All participants received standardized oral hygiene instructions. The prescribed dosage was 10 mL of mouthwash, used twice daily, with a 60-second rinse, for the entire 14-day period. Subjects were instructed to avoid food intake, toothbrushing, and toothpaste use for at least 1 hour after administration to prevent interference with the product.
2.2.1. Inclusion Criteria
Inclusion criteria were as follows: age ≥ 18 years; presence of at least one well-defined aphthous ulcer at baseline; and a clinical diagnosis of recurrent aphthous stomatitis (RAS). Patients were enrolled if they presented with at least one clearly identifiable aphthous lesion and were older than 18 years at the time of inclusion.
2.2.2. Exclusion Criteria
The following exclusion criteria have been used for the exclusion from the clinical protocol: intolerance or allergy to the compound or mouthwash components, hematologic disorders including anemia, deficiency of iron, vitamin B12 and/or folic acid; systemic disorders of the gastrointestinal tract including ulcerative colitis, Crohn’s disease, Behcet’s syndrome associated with RAS, alcoholism and tabagism; vitamins, antibiotic therapy, antihistamine drug, immunomodulatory agents administration of nonsteroidal anti-inflammatory drugs or mouthwash was considered an exclusion factor is performed within 72 hours from the study allocation; pregnant or breastfeeding women subjects.
2.3. The ingredients of the mouthwashes.
The mouthwash studied is a film-forming formulation. The DNA components can improve viscosity, thereby enhancing mucosal hydration and trophism. The objective of mouthwash administration is to reduce recurrence and improve prognosis. The formulation is characterized by VP/VA copolymer, Carbomer, Cellulose gum, PVM/MA copolymer, Hydrolyzed RNA/DNA, in water solution (Afterapid Curasept, Saronno – VA - Italy). The placebo mouthwash was organoleptically identical.
2.4. Randomization and Blinding Protocol
The randomization protocol was implemented using computer-generated random codes (A, B) inserted into sequentially numbered, sealed, opaque envelopes provided by the study consultant. The blinded operators were the visiting doctor, the examiner, and the data analyzer.
Product masking (test and placebo) has been achieved through a process designed to make the products indistinguishable from mouthwash. The mouthwash was poured into identical vials labeled with a letter (A, B). The random allocation is made by opening the sequentially numbered sealed pouch just before treatment.
The masking was conducted by a blinded operator who performed all measurements. The codes (A, B) were revealed at the end of the study, with Group I receiving the placebo (A).
2.5. Study Outcome
The following study outcomes were evaluated at 7 days and 2 weeks after the initial treatment, including pain intensity (VAS) and ulcer dimensions.
2.6. Thermal Infrared Imaging
The infrared thermography assessment has been conducted in a controlled environment (T: 20–24 C, humidity: 52%, no direct ventilation). The environmental conditions have been monitored by a dedicated sensor (Atmo-Tube, San Francisco, CA, USA). The machine can assess relative humidity (RH) at regular intervals. The infrared thermal assessment has been performed through a dedicated camera (FLIR SC660 QWIP, Flir Systems, Danderyd, Sweden) [19]. (Fig. 1)
2.7. Statistical Analysis
The statistical findings have been included in summary tables by variable. General descriptive statistics for continuous outcome measures include an “n” value (count of observed values), the mean with its 95% CI, standard deviation, median, minimum, and maximum. For categorical variables, the counts and percentages of subjects for each level are presented. The study hypothesis has been tested using the Kruskal-Wallis test at a 5% significance level. All statistical comparisons will be conducted at the 0.05 significance level. Version 9.0 of the Graphpad software (Prism, San Diego, CA, USA) will be used for analysis. The power analysis indicated a population sample with 29 patients/group (80% power) (means: 0.820; standard deviation: 1.80) with p<0.05. Moreover, a 3% dropout compensation has been considered. The final population sample size was 30 patients per experimental group.
3. Results
No dropouts or adverse events were recorded in the trial phases (14 days). The average age of enrolled patients was 36.43±8.66 years; the cohort comprised 58.33% women (n=35) and 41.67% men (n=25) (Fig. 2).
Group I
V1-Baseline
The baseline USS score showed an average of 32.7±5.3 (95% CI: 30.73–34.77). The pain VAS score was 6.1±2.1 (95% CI: 5.3–6.9) at the T0 time point. The ulcer count and size were 4.7±1.1 (95% CI: 4.2–5.1) and 7.4±3.1mm (95% CI:6.2–8.5), respectively (Tab. 2).
V2-1st week
The USS scoring measured after 1 week reported a mean of 31.7±4.4 (95% CI: 30–33). The VAS after 1 week from the first treatment was 5.2±1.4 (95% CI: 4.7–5.7). The ulcer count and size in millimeters were 3.4±1.4 (95% CI: 2.9–3.9) and 5.5±2.2mm (95% CI: 4.7–6.4), respectively (Tab. 3).
V3-2nd week
The 2-week USS score was 28.3±5.9 (95% CI: 26.1–30.5), and the pain score calculated by VAS was 4.6±1.9 (95% CI: 3.9–5.3). The lesion count and size decreased to 2.6±1.3 (95% CI: 2.1–3.1) and 3.8±2.3 (95% CI: 2.9–4.6), respectively (Tab. 4).
Group II
V1-Baseline
The baseline USS was 32.43±4.4 (95% CI: 30.8–34.1). The VAS score showed a mean of 6.5±1.7 (95% CI: 5.9–7.2). The lesions count and dimensions were 3.4±1.3 (95% CI: 2.9) and 6.7±2.4 (95% CI: 5.8–7.6), respectively (Tab. 5).
V2-1st week
The 1-week assessment of the USS score showed an average of 24.8±4.5 (95% CI: 23.1–26.4). The VAS pain was 2.7±1.3 (95% CI: 2.2–3.1). The lesion count and dimension mean were 1.5±1 (95% CI: 1.1–1.9) and 3.6±1.7 (95% CI: 2.9–4.2) (Tab. 6).
V3-2nd week
The USS recorded 2 weeks after treatment was 17.0±2.5 (95% CI: 16.1–17.9). The VAS score was 2.3±1.4 (95% CI: 1.8–2.9). The lesions count and size were 1.2±0.9 (95% CI: 0.8–1.5) and 2.5±1.9 (95% CI: 1.8–3.2) (Tab. 7).
Inter-groups Pairwise comparisons
The significance of pairwise comparisons among the study groups has been tested using the Kruskal-Wallis test. At baseline, the lesion count did not differ significantly between groups I and II (p=0.09). A significant difference was reported when comparing the means at the 1-week and 2-week timepoints (p<0.01). No significant differences between groups I and II have been detected, considering the ulcer dimensions measured at baseline (p>0.05). On the other hand, a statistically significant difference has been detected at 1- and 2-week follow-up (p<0.01). The VAS pain score was not significant at the baseline (p>0.05). A significant difference in pain symptoms was detected at 1 and 2 weeks between Group I and Group II (p<0.01). No significant differences have been detected when comparing groups I and II based on infrared thermal measurements (p>0.05). at baseline, after 1 week, and 2 weeks (p>0.01) (Fig 3–4; Tab 8).
4. Discussion
The etiopathology of the recurrent aphthous stomatitis is not completely clear and contains a set of disorders that could trigger this disease [20]. Histologically, several studies reported focal alterations occurring in the pre-ulcerative phases that are characterized by the increasing infiltration of lymphocytes, keratinocyte vacuolization, and T-cell mediators’ response, including tumor necrosis factor alpha (TNF), interleukin-2 (IL-2), IL-10, or interleukins IL-1 and IL-6 overexpression [21–22]. The main effect of these alterations is that CD8+ cells aggregate to cytotoxic effect against epithelial cells, producing mucosal ulcers [23].
Some predisposing factors have been detected in literature, including physical injury exposure, smoke and tobacco consumption, gastrointestinal disorders, immunosuppression, and other syndromic conditions, including Crohn’s and Behcet diseases [24]. Moreover, deficiencies of Vitamins (B12), iron, and folic acid seem to increase the frequency and the severity of recurrent aphthous stomatitis significantly.
Microbiologically, various bacteria have been identified with a higher prevalence in aphthous ulcers, but their active role was not specifically associated with the disease [9]. A hypothetical correlation has been proposed between S. oralis, S. sanguis, and S. mitis and the recurrent form of aphthous ulcers [9]. Moreover, A. johnsonii has been reported as a possible agent correlated to a higher risk of recurrent aphthous stomatitis. Three different manifestations have been reported in literature: minor aphthous ulcers, major lesions, and herpetiform manifestations [2,5,7]. The minor forms are characterized by a lower age of onset (first/second decade), a mean size of 1–5 mm, and disease resolution within 14 days. These forms represent ~80% of the total epidemiological sample. The major forms are clinically characterized by more durable lesions, larger size (>1cm), and the potential formation of scars. The herpetiform manifestation is rare, with a higher prevalence in female subjects, and can develop simultaneously in a count of lesions ranging from 10 to 100 units [9]. Several products and treatments have been proposed in literature, including topical agents, anti-inflammatory drugs, corticosteroids, and antimicrobials. The use of potent immunomodulatory agents has been proposed for the treatment of the more severe forms of aphthous stomatitis, including anti-TNF agents, thalidomide, and monoclonal anti-TNF antibodies [6,20,25–26]. The administration of antiseptic agents has been proposed to reduce the duration of aphthous stomatitis lesions and increase the ulcer-free period. The action could be associated with the active and secondary roles played by the oral microbial flora in triggering and sustaining the disease. Clinically, various approaches have been described in the literature as symptomatic treatments that do not appear to eradicate disease or reduce recurrence frequency in adult and/or pediatric patients. Although no definitive therapies have been identified, several active agents have been suggested, including 0.2% chlorhexidine mouthwash, topical benzidamine, zinc chloride, and polycresol. Moreover, the efficacy of tetracycline and 1% lidocaine has been reported, especially for high-recurrence and refractory oral lesions [17,27–28]. The study population included in the present survey was demographically homogeneous with respect to the independent study variables (age, gender), and no subjects were lost to follow-up. The primary limitation of the investigation was the short follow-up period. In fact, measuring the efficacy of the mouthwash compound in reducing lesion recurrence frequency was not applicable. In addition, the wide variability in RAS clinical course was not technically captured in cases of associations with syndromic disorders and/or in the presence of comorbidities due to this specific methodological choice. Moreover, the cross-effects of these independent variables could be taken for future studies and trials. Considering the homogeneity of the population examined, no significant differences have been detected between study groups for all variables, including the USS scoring assessment, clinical pain, and thermal variations at the experimental baseline. After 1 week, a statistically significant difference was detected, showing a misalignment of the parameters. In fact, the group II patients reported a decrease in VAS pain and a significant reduction in count and lesion size. At experimental time V3, i.e. after 2 weeks of treatment, a statistically significant difference in the primary assessment indices is confirmed with a more favorable clinical picture in group II both in terms of pain measured on the VAS scale, and in terms of count and size of residual lesions. Thermographic measurements showed no significant differences between groups (p>0.05).
Given the wide variability of the clinical picture related to the disease in question, as well as the intrinsic characteristics and etiopathogenesis, the course is widely variable and subject to high recurrence and recurrence. The same symptomatology can represent in severe cases a source of high discomfort for the patient, as regions constantly subject to functional trauma and which can sometimes also limit oral hygiene maneuvers [5,29–31]. It is evident that in subjects with a high recurrence index, it seems appropriate to control these aspects also in order to prevent a secondary deterioration of plaque and inflammation indices affecting the mucous membranes and gingival tissues [18]. Regarding the temperature recording, the infrared thermal detection has been used for the present assessment. The thermal detection has been described in literature as a useful adjuvant diagnostic tool for early diagnosis for several diseases including inflammatory and cutaneous pathologies including skin cancer. However considering the limits of this methodology, the thermal sensitivity could be insufficient in several conditions including oral cavity environment while the detection could be sensibly affected in insidious localizations and small size lesions. Furthermore, the cause of the disease is also positively influenced by group II patients undergoing treatment, demonstrating a reduction in the count of lesions and size. It is evident from the literature that secondary factors such as pain reduction and improved control of factors such as bacterial plaque may further constitute an additional enhancement effect of treatment that may facilitate its course and prognosis [18]. Given the limited duration of the present study design, it was not possible to evaluate the effects of treatment on relapse rates. This technique has been used for different applications including in vitro studies for dental implant preparation heating, medical diagnostic supplement and also for occupational applications [19,32–33]. For an internal cavity assessment, this technique could sensibly be affected by biases regarding the relative humidity of the region, the reflectivity of the tissues and the confounding effects of surgical retractors. In this present investigation, no differences in surface temperature have been observed comparing group test and control at different timepoints. In this way, further investigation with a higher sample size is strongly recommended to test this particular variable to point out the significant level of the outcome.
5. Conclusions
In accordance with the findings reported by the present investigation, the device compound seems to ameliorate the ulcers prognosis with an increase of the disease-free period. A statistically significant decrease of pain and symptoms was reported with no adverse or undesirable effects emerged by the present trial.
Author Contributions
Conceptualization, AS; methodology, AS, FL; validation, AS, FL; formal analysis, FL; investigation, AS, FL, SAG, GA; data curation, AS, FL; writing — original draft preparation, AS, FL, SAG, GA; writing — review and editing, AS, FL, SAG, GA; visualization, AS, FL; All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Territorial Ethics Committee of the Abruzzi Region, Italy for studies involving humans Prot. n. RA/0362820 del 05/09/2023. The present study was registered on clinicaltrials.gov database (Identifier: NCT07121361).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
All experimental data to support the findings of this study are available contacting the corresponding author upon request.
Acknowledgments
None.
Conflicts of Interest
The authors declare no conflicts of interest.
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| Characteristics of the lesion | Score | Description of the USS | |
|---|---|---|---|
| Mean concomitant lesion number | Max score = 20 | ||
| Mean ulcers size (in mm) | Max score = 20 | ||
| Mean disease duration (in weeks) | Score = number of 1/2 weeks i.e. Half a week (3 days) scores 1, one and a half weeks (10 days) scores 3. Maximum score = 10 |
||
| Injury-free phase (in weeks) | Score = 10 minus the average ulcer-free period in weeks Maximum score = 10 (never ulcer-free) |
||
| Patient-perceived pain (scaled from 0–10) | |||
| Site | Group 1 Labial and Buccal mucosa and sulcus Soft palate Belly of the tongue Mouth Floor Group 2 Hard palate Gum Alveolar ridge Tongue Tonsils, Uvula and Oropharynx mucosa |
Score = total of sites involved 1 for each site of group 1 (non-keratinized mucosa) 2 for each site of group 2 (keratinized, specialized) Maximum score = 10 |
|
| Scarring | Yes/No | USS Total |
| USS SCORE | Number | Size | Duration [*] | Free Period [*] | Pain | Site | Temperature | |
|---|---|---|---|---|---|---|---|---|
| Average | 32,70 | 4,667 | 7,367 | 3,400 | 4,333 | 6,133 | 6,800 | 37,21 |
| SD | 5,286 | 1,124 | 3,079 | 0,8944 | 1,446 | 2,113 | 1,730 | 0,8271 |
| SE | 0,9651 | 0,2053 | 0,5622 | 0,1633 | 0,2641 | 0,3858 | 0,3159 | 0,1510 |
| Lower 95% Confidence Interval | 30,73 | 4,247 | 6,217 | 3,066 | 3,793 | 5,344 | 6,154 | 36,90 |
| Upper 95% Confidence Interval | 34,67 | 5,087 | 8,516 | 3,734 | 4,873 | 6,922 | 7,446 | 37,52 |
| USS SCORE | Number | Size | Duration [*] | Free Period [*] | Pain | Site | Temperature | |
|---|---|---|---|---|---|---|---|---|
| Average | 31,67 | 3,400 | 5,533 | 2,000 | 10,00 | 5,200 | 5,533 | 37,30 |
| SD | 4,358 | 1,380 | 2,193 | 0,000 | 0,000 | 1,448 | 1,655 | 0,6037 |
| SE | 0,7956 | 0,2519 | 0,4004 | 0,000 | 0,000 | 0,2644 | 0,3022 | 0,1102 |
| Lower 95% Confidence Interval | 30,04 | 2,885 | 4,714 | 2,000 | 10,00 | 4,659 | 4,915 | 37,08 |
| Upper 95% Confidence Interval | 33,29 | 3,915 | 6,352 | 2,000 | 10,00 | 5,741 | 6,151 | 37,53 |
| USS SCORE | Number | Size | Duration [*] | Free Period [*] | Pain | Site | Temperature | |
|---|---|---|---|---|---|---|---|---|
| Average | 28,28 | 2,600 | 3,767 | 3,833 | 9,917 | 4,567 | 3,600 | 36,87 |
| SD | 5,959 | 1,329 | 2,223 | 0,5307 | 0,2653 | 1,888 | 1,850 | 0,6280 |
| SE | 1,088 | 0,2426 | 0,4059 | 0,09689 | 0,04844 | 0,3447 | 0,3377 | 0,1147 |
| Lower 95% Confidence Interval | 26,06 | 2,104 | 2,936 | 3,635 | 9,818 | 3,862 | 2,909 | 36,64 |
| Upper 95% Confidence Interval | 30,51 | 3,096 | 4,597 | 4,031 | 10,02 | 5,272 | 4,291 | 37,11 |
| USS SCORE | Number | Size | Duration [*] | Free Period [*] | Pain | Site | Temperature | |
|---|---|---|---|---|---|---|---|---|
| Average | 32,43 | 3,400 | 6,700 | 4,233 | 6,400 | 6,533 | 5,167 | 37,31 |
| SD | 4,352 | 1,276 | 2,366 | 1,357 | 1,303 | 1,655 | 1,683 | 0,5501 |
| SE | 0,7946 | 0,2329 | 0,4319 | 0,2477 | 0,2378 | 0,3022 | 0,3073 | 0,1004 |
| Lower 95% Confidence Interval | 30,81 | 2,924 | 5,817 | 3,727 | 5,914 | 5,915 | 4,538 | 37,11 |
| Upper 95% Confidence Interval | 34,06 | 3,876 | 7,583 | 4,740 | 6,886 | 7,151 | 5,795 | 37,52 |
| USS SCORE | Number | Size | Duration [*] | Free Period [*] | Pain | Site | Temperature | |
|---|---|---|---|---|---|---|---|---|
| Average | 24,77 | 1,5 | 3,567 | 2,000 | 9,867 | 2,667 | 5,167 | 36,88 |
| SD | 4,462 | 0,9738 | 1,736 | 0,000 | 0,3457 | 1,269 | 1,683 | 0,5671 |
| SE | 0,8146 | 0,1778 | 0,3169 | 0,000 | 0,06312 | 0,2316 | 0,3073 | 0,1035 |
| Lower 95% Confidence Interval | 23,10 | 1,136 | 2,919 | 2,000 | 9,738 | 2,193 | 4,538 | 36,67 |
| Upper 95% Confidence Interval | 26,43 | 1,864 | 4,215 | 2,000 | 9,996 | 3,140 | 5,795 | 37,09 |
| USS SCORE | Number | Size | Duration [*] | Free Period [*] | Pain | Site | Temperature | |
|---|---|---|---|---|---|---|---|---|
| Average | 16,98 | 1,167 | 2,533 | 3,633 | 2,150 | 2,333 | 5,167 | 36,74 |
| SD | 2,455 | 0,9129 | 1,852 | 0,7184 | 3,966 | 1,422 | 1,683 | 0,5183 |
| SE | 0,4482 | 0,1667 | 0,3381 | 0,1312 | 0,7240 | 0,2597 | 0,3073 | 0,09462 |
| Lower 95% Confidence Interval | 16,07 | 0,8258 | 1,842 | 3,365 | 0,6692 | 1,802 | 4,538 | 36,54 |
| Upper 95% Confidence Interval | 17,90 | 1,508 | 3,225 | 3,902 | 3,631 | 2,864 | 5,795 | 36,93 |
| Ulcers Number | |||||
|---|---|---|---|---|---|
| Dunn’s post hoc | Mean rank diff, | Significance | - | P Value | |
| GI-baseline vs. GI-1 week | 36,20 | No | ns | 0,0946 | A–B |
| GI-baseline vs. GI-2 week | 60,02 | Yes | **** | <0,0001 | A–C |
| GI-baseline vs. GII-baseline | 36,23 | No | ns | 0,0938 | A–D |
| GI-baseline vs. GII-1 week | 97,38 | Yes | **** | <0,0001 | A–E |
| GI-baseline vs. GII-2weeks | 108,2 | Yes | **** | <0,0001 | A–F |
| GI-1 week vs. GI-2 weeks | 23,82 | No | ns | >0,9999 | B–C |
| GI-1 week vs. GI-baseline | 0,03333 | No | ns | >0,9999 | B–D |
| GI-1 week vs. GII- 1 week | 61,18 | Yes | **** | <0,0001 | B–E |
| GI-1 week vs. GII -2 weeks | 71,97 | Yes | **** | <0,0001 | B–F |
| GI-2 weeks vs. GII -baseline | −23,78 | No | ns | >0,9999 | C–D |
| GI-2 weeks vs. GII -1 week | 37,37 | No | ns | 0,0721 | C–E |
| GI-2 weeks vs. GII -2 weeks | 48,15 | Yes | ** | 0,0042 | C–F |
| GII II-baseline vs. GII -1 week | 61,15 | Yes | **** | <0,0001 | D–E |
| GII- baseline vs. GII -2 weeks | 71,93 | Yes | **** | <0,0001 | D–F |
| GII-1 week vs. GII -2 weeks | 10,78 | No | ns | >0,9999 | E–F |
| VAS Pain | |||||
| GI-baseline vs. GI-1 week | 18,28 | No | ns | >0,9999 | A–B |
| GI-baseline vs. GI-2 week | 31,95 | No | ns | 0,2448 | A–C |
| GI-baseline vs. GII-baseline | −10,45 | No | ns | >0,9999 | A–D |
| GI-baseline vs. GII-1 week | 80,40 | Yes | **** | <0,0001 | A–E |
| GI-baseline vs. GII-2weeks | 85,42 | Yes | **** | <0,0001 | A–F |
| GI-1 week vs. GI-2 weeks | 13,67 | No | ns | >0,9999 | B–C |
| GI-1 week vs. GI-baseline | −28,73 | No | ns | 0,4618 | B–D |
| GI-1 week vs. GII- 1 week | 62,12 | Yes | **** | <0,0001 | B–E |
| GI-1 week vs. GII -2 weeks | 67,13 | Yes | **** | <0,0001 | B–F |
| GI-2 weeks vs. GII -baseline | −42,40 | Yes | * | 0,0216 | C–D |
| GI-2 weeks vs. GII -1 week | 48,45 | Yes | ** | 0,0041 | C–E |
| GI-2 weeks vs. GII -2 weeks | 53,47 | Yes | *** | 0,0009 | C–F |
| GII II-baseline vs. GII -1 week | 90,85 | Yes | **** | <0,0001 | D–E |
| GII- baseline vs. GII -2 weeks | 95,87 | Yes | **** | <0,0001 | D–F |
| GII-1 week vs. GII -2 weeks | 5,017 | No | ns | >0,9999 | E–F |
| Lesion Size | |||||
| GI-baseline vs. GI-1 week | 25,13 | No | ns | 0,8968 | A–B |
| GI-baseline vs. GI-2 week | 59,00 | Yes | *** | 0,0001 | A–C |
| GI-baseline vs. GII-baseline | 3,950 | No | ns | >0,9999 | A–D |
| GI-baseline vs. GII-1 week | 63,65 | Yes | **** | <0,0001 | A–E |
| GI-baseline vs. GII-2weeks | 85,57 | Yes | **** | <0,0001 | A–F |
| GI-1 week vs. GI-2 weeks | 33,87 | No | ns | 0,1680 | B–C |
| GI-1 week vs. GI-baseline | −21,18 | No | ns | >0,9999 | B–D |
| GI-1 week vs. GII- 1 week | 38,52 | No | ns | 0,0588 | B–E |
| GI-1 week vs. GII -2 weeks | 60,43 | Yes | **** | <0,0001 | B–F |
| GI-2 weeks vs. GII -baseline | −55,05 | Yes | *** | 0,0006 | C–D |
| GI-2 weeks vs. GII -1 week | 4,650 | No | ns | >0,9999 | C–E |
| GI-2 weeks vs. GII -2 weeks | 26,57 | No | ns | 0,6993 | C–F |
| GII II-baseline vs. GII -1 week | 59,70 | Yes | *** | 0,0001 | D–E |
| GII- baseline vs. GII -2 weeks | 81,62 | Yes | **** | <0,0001 | D–F |
| GII-1 week vs. GII -2 weeks | 21,92 | No | ns | >0,9999 | E–F |
| Infrared Thermal Assessment | |||||
| Dunn’s post hoc | Mean rank diff, | Significance | - | P Value | |
| GI-baseline vs. GI-1 week | −7,933 | No | ns | >0,9999 | A–B |
| GI-baseline vs. GI-2 week | 30,07 | No | ns | 0,3770 | A–C |
| GI-baseline vs. GII-baseline | −10,62 | No | ns | >0,9999 | A–D |
| GI-baseline vs. GII-1 week | 28,78 | No | ns | 0,4808 | A–E |
| GI-baseline vs. GII-2weeks | 37,90 | No | ns | 0,0714 | A–F |
| GI-1 week vs. GI-2 weeks | 38,00 | No | ns | 0,0698 | B–C |
| GI-1 week vs. GI-baseline | −2,683 | No | ns | >0,9999 | B–D |
| GI-1 week vs. GII- 1 week | 36,72 | No | ns | 0,0937 | B–E |
| GI-1 week vs. GII -2 weeks | 45,83 | Yes | ** | 0,0096 | B–F |
| GI-2 weeks vs. GII -baseline | −40,68 | Yes | * | 0,0367 | C–D |
| GI-2 weeks vs. GII -1 week | −1,283 | No | ns | >0,9999 | C–E |
| GI-2 weeks vs. GII -2 weeks | 7,833 | No | ns | >0,9999 | C–F |