Table 2: Summary of eligible RCT studies.

Reference

Country, Study Type, Total sample size

Interventions, sample size per group

Control intervention, sample size

Inclusion criteria

Gender and age (average ± SD, range in years)

Amanlou, et al. [11]

Iran, RCT, double blinded,

N = 60

S. khuzistanica extract 3x day, n = 20

S. khuzistanica essential oil,

n = 20

Hydroalcoholic vehicle (placebo),

n = 20

(1) History of RAS

(2) Currently suffering from ulceration located on the oral mucosa

28M/32F

28.48

10-64 years

Atanasovska Stojanovska, et al. [13]

Macedonia, RCT, double blinded

N = 20

Proaftol spray, n = 10

Control spray, n = 10

(1) RAS with a frequency of at least 3-4 times a year.

No gender specified

20-30 years

Babaee, et al. [14]

Iran, randomized, double-blind, controlled before-after clinical trial

N = 40

Myrtle oral paste,

n = 40

Placebo oral paste,

n = 40

(1) 18 years of age or older,

(2) Clear history of RAS occurring at least twice a year,

(3) Presenting with 1-3 aphthous ulcers (< 48 h duration), measuring no more than 10 mm in diameter,

(4) Had an expectation that their ulcers normally takes > 5 days to resolve without treatment,

(5) No underlying medical or hematological cause for their ulceration.

17M/23 F

29.5 ± 10.3

18-58 years

Babaee, et al. [15]

Iran, RCT, double blinded

N = 40

Aloe vera gel, n = 20

Placebo gel,

n = 20

(1) Aged between 15 and 35 years

(2) Minor recurrent aphthous singular lesions on their buccal mucosa and mucosal zone of the lips (after a medical diagnosis of RAS minor)

(3) Without any other medical complications

(4) Patients had noticed oral lesions during the last two days

22M/18F

Intervention group: 27.95 ± 7.96 years

Placebo: 29.25 ± 7.48 years

El-Haddad, et al. [16]

Kingdom Saudi Arabia,

RCT, single-blinded

N = 94

Honey-treated group,

n = 34

0.1% triamcinolone acetonide,

n = 30

Orabase control group, n = 30

(1) Males and females aged from 18-60 years old.

(2) Positive history of recurrent aphthous ulceration that normally last more than 5 days each episode without treatment.

(3) Presence of 1-5 aphthous ulcers that present for less than 48 hours without treatment.

(4) Ulcer size not greater than 5 mm in diameter.

(5) The ulcers are available for topical application of the treated agent.

28M/66F

18-60 years

Hoseinpour, et al. [17]

Iran, RCT, double-blinded

N = 50

Mouth wash with Rosa damascene 1 minute,

N = 25

Placebo,

n = 25

(1) At least one aphthous ulcer measuring no more than 10 mm in diameter;

(2) Duration of the ulcer(s) ≤ 48 hours;

(3) Only patients with minor or herpetic form ulcerations were included.

27M/23F

Rosa: 34.4 ± 9.6 years;

Placebo: 33.6 ± 14.4

21-59 years

Jiang, et al. [10]

China

RCT, double-blinded

N = 84

Berberine gelatin (10 g) containing 50 mg berberine,

n = 42

Placebo agent, n = 42

(1) Both genders aged 18 to 50 years;

(2) A history of RAS for a minimum of 6 months with an average of 1 to 2 outbreaks per month and 1 to 5 minor aphthae per outbreak;

(3) No analgesics use or other drugs curing oral ulcer during the study;

(4) 1 to 3 aphthous ulcerations with a size _5 and _10 mm in diameter; for more than 1 ulceration, a distance between ulcerations of more than 1 cm;

(5) Time of ulceration onset within 48 hours;

(6) Ulcers in locations that are easily accessible for evaluation and treatment.

Gender

Berberine: 14

M/28F

Placebo: 10M/32 F

Berberine: 30.86 ± 7.53

19-51 years

Placebo: 31.19 ± 6.00

20-45 years

Liu, et al. [18]

China, RCT, double blinded,

N = 240 randomized, N = 227

Completed the study

Toothpaste 0.65% Yunnan Baiyao,

n = 113

Placebo toothpaste,

n = 114

(1) Both male and female aged 18 to 65-years-old;

(2) Patients diagnosed as minor recurrent aphthous stomatitis with the duration of each ulcer in excess of 5 days;

(3) Fresh ulcers available with less than 72 hours eruption.

53M/174F

Yunnan: 31.9 ± 10.9 Placebo: 31.4 ± 11.8

Mansour, et al. [19]

 

Saudi Arabia, RCT, double blinded

N = 90

Mucoadhesive gel with aloe vera,

n = 30

Mucoadhesive gel with myrrh extract,

n = 30

Mucoadhesive gel (placebo),

n = 30

(1) Presenting with 1-3 minor fresh RAS lesions, with duration < 48 h, and not greater in diameter than 5 mm.

(2) If any participant had more than one ulcer, the one selected for evaluation was the most recent one.

38M/52F

31.7 ± 8.4

18-36 years

Pourahmad, et al. [20]

 

 

Iran,

RCT, double

blinded

N = 93

Camel thorn distillate,

n = 49

Distilled water, n = 44

 

(1) An aphthous lesion on their oral mucosa;

(2) History of recurrent similar lesions.

49M/44F

Camel Thorn: 27.4 years

Placebo: 31.8 years

Yang, et al. [12]

 

China,

RCT,

double-

Blinded

N = 80

Pudilan toothpaste,

n = 40

 

Placebo paste, n = 40

 

(1) 18 to 62-years-old; (2) have been confirmed as having minor aphthous ulcers (MiAUs) with 1-3 ulcerous lesions and a maximum lesion diameter < 10 mm;

(2) Have had MiAUs diagnosed at least 6 months prior to this study and not have required medication for more than 5 days to recover from any episode;

(3) Have had recent ulcerous lesions occurring within 48h prior to the study and not received any treatment.

Unknown gender and age

MiAUs: Minor Aphthous Ulcers.