Protocol summary
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Study aim
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The aim of the present clinical trial is to compare the effectiveness of Origanum vulgare vaginal cream with clotrimazole vaginal cream on the treatment of vulvovaginal candidiasis.
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Design
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A phase 3 randomized clinical trial with a control group, parallel groups, triple-blind design, conducted on 98 patients. Randomization will be performed using permuted random blocks of sizes 4, 6, and 8, utilizing the website www.randomization.com.
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Settings and conduct
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This study will be a triple-blind, randomized controlled clinical trial conducted on 98 eligible women with vulvovaginal candidiasis who visit the sampling centers. In this study, participants will be randomly allocated using permuted block randomization with block sizes of 4, 6, and 8 into two groups: the control group (clotrimazole cream) and the intervention group (Origanum vulgare cream).
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Participants/Inclusion and exclusion criteria
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In this study, women aged 18 to 45 years with clinical symptoms of vulvovaginal candidiasis, positive results from direct microscopy and culture of vaginal discharge tests and no known sensitivity to Origanum vulgare or clotrimazole will be included.
Pregnant and breastfeeding women, those with abnormal vaginal bleeding, known chronic diseases such as diabetes, hypertension and etc., recent use of broad-spectrum antibiotics or oral/vaginal medications related to genital infections within the past two weeks will be excluded from the study.
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Intervention groups
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Intervention Group: Vaginal cream containing 0.2% Origanum vulgare essential oil (one full applicator containing 5 grams of the vaginal cream every night for one week)
Control Group: 1% clotrimazole vaginal cream (one full applicator containing 5 grams of the vaginal cream every night for one week)
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Main outcome variables
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Clinical and laboratory indicators of vulvovaginal candidiasis
General information
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Reason for update
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This update was undertaken to complete, clarify, and organize the pre-specified variables documented in the study protocol; ensure precise and complete alignment of the timing of the follow-up assessments conducted with the information registered in the IRCT; provide additional information regarding the source and site of preparation of the vaginal creams used in the study; and make certain editorial and grammatical revisions to the registered information. These revisions were made solely to enhance transparency, complete the registered information, and ensure consistency between the registered documentation and the methodology actually implemented in the study, and do not involve any changes to the nature of the study, the type of intervention, the study groups, or the primary study procedures.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20241221064119N1
Registration date:
2024-12-25, 1403/10/05
Registration timing:
prospective
Last update:
2026-08-17, 1405/05/26
Update count:
4
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Registration date
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2024-12-25, 1403/10/05
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2025-04-19, 1404/01/30
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Expected recruitment end date
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2025-07-21, 1404/04/30
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Comparison the effect of Origanum vulgare vaginal cream with clotrimazole vaginal cream on treatment of vulvovaginal candidiasis in reproductive aged women
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Public title
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Investigation the effect of Origanum vulgare vaginal cream on treatment of vulvovaginal candidiasis
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Being married
Being monogamous
The presence of clinical symptoms indicative of vulvovaginal candidiasis
Positive result of the direct microscopy test of vaginal discharge
Positive result of the vaginal discharge culture test
No history of any known medical condition
No allergy to Origanum vulgare plant and clotrimazole
Completion of a written informed consent form
Exclusion criteria:
Pregnancy
Breastfeeding
Menopause
Abnormal vaginal bleeding
Body mass index (BMI) ≥ 30
History of recurrent vulvovaginal candidiasis infections (4 or more episodes per year)
History of known chronic diseases such as diabetes, hypertension, heart disease, immune system disorders and epilepsy
Use of broad-spectrum antibiotics within the past two weeks
Use of immunosuppressive drugs, corticosteroids or contraceptive pills
Use of oral or vaginal medications related to genital infections within the past two weeks
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Age
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From 18 years old to 45 years old
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Gender
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Female
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Phase
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3
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Groups that have been masked
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- Participant
- Investigator
- Data analyser
- Data and Safety Monitoring Board
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Sample size
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Target sample size:
98
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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In this study, we will use the method of permuted block randomization to randomly assign participants to the intervention and control groups. The block sizes in this two-group clinical trial will be set at 4, 6, and 8 (in this method, the number of participants assigned to each group within a block is equal). To ensure allocation concealment, we will use random allocation concealment, which refers to the method used to implement the random sequence for participants in the study, such that the assigned group is not known before allocation. In this study, 1% clotrimazole vaginal cream, under sterile conditions, will be filled into tubes identical to those used for Origanum vulgare vaginal cream. These medications will be labeled as A and B by a pharmacist. Thus, the clotrimazole and Origanum vulgare vaginal creams will be identical in appearance, such as packaging and color, ensuring that neither the researcher nor the patient is aware of the type of vaginal cream being administered. The medications used in this study will be placed in sealed envelopes and assigned to each participant according to the randomized list by an individual not involved in the study.
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Blinding (investigator's opinion)
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Triple blinded
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Blinding description
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This study will be conducted in a triple-blind manner, meaning that the researcher, the study participants, and the data analyst (statistician) will all be completely unaware of the type of vaginal medication being used by the participants. Clotrimazole and Origanum vulgare vaginal creams will be dispensed into identical tubes and labeled as A and B by the pharmacist. Thus, the clotrimazole and Origanum vulgare vaginal creams will be identical in appearance, including packaging and color. The medications used in this study will be placed in sealed envelopes and assigned to each participant according to a randomized list prepared by an individual outside the study.
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2024-12-07, 1403/09/17
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Ethics committee reference number
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IR.AJUMS.REC.1403.492
Health conditions studied
1
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Description of health condition studied
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Vulvovaginal candidiasis
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ICD-10 code
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B37.3
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ICD-10 code description
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Candidiasis of vulva and vagina
Primary outcomes
1
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Description
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Composite clinical-mycological status of vulvovaginal candidiasis
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Timepoint
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2 weeks after the intervention
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Method of measurement
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Taking the patient's history, clinical examination, Gram staining of vaginal discharge smear and vaginal discharge culture on CHROMagar candida medium (complete resolution of the specific clinical signs and symptoms of vulvovaginal candidiasis, together with a negative direct smear and vaginal discharge culture for Candida species)
Secondary outcomes
1
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Description
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Vulvovaginal itching
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Timepoint
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Before the intervention, and 2 and 4 weeks after the intervention
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Method of measurement
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In-person history taking at pre-intervention and first follow-up visits and telephone history taking at the second follow-up visit
2
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Description
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Vulvovaginal burning
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Timepoint
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Before the intervention, and 2 and 4 weeks after the intervention
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Method of measurement
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In-person history taking at pre-intervention and first follow-up visits and telephone history taking at the second follow-up visit
3
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Description
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Vulvovaginal irritation
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Timepoint
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Before the intervention, and 2 and 4 weeks after the intervention
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Method of measurement
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In-person history taking at pre-intervention and first follow-up visits and telephone history taking at the second follow-up visit
4
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Description
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External dysuria
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Timepoint
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Before the intervention, and 2 and 4 weeks after the intervention
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Method of measurement
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In-person history taking at pre-intervention and first follow-up visits and telephone history taking at the second follow-up visit
5
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Description
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Dyspareunia
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Timepoint
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Before the intervention, and 2 and 4 weeks after the intervention
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Method of measurement
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In-person history taking at pre-intervention and first follow-up visits and telephone history taking at the second follow-up visit
6
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Description
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Vulvovaginal erythema
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Timepoint
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Before the intervention and 2 weeks after the intervention
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Method of measurement
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Clinical examination
7
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Description
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Vulvovaginal edema
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Timepoint
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Before the intervention and 2 weeks after the intervention
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Method of measurement
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Clinical examination
8
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Description
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Curdy vaginal discharge
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Timepoint
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Before the intervention and 2 weeks after the intervention
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Method of measurement
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Clinical examination
9
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Description
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Vulvovaginal excoriation
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Timepoint
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Before the intervention and 2 weeks after the intervention
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Method of measurement
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Clinical examination
10
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Description
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Vaginal pH
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Timepoint
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Before the intervention and 2 weeks after the intervention
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Method of measurement
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pH indicator strips
11
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Description
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Gram staining of vaginal discharge smear test
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Timepoint
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Before the intervention and 2 weeks after the intervention
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Method of measurement
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Microscopic examination of a stained vaginal discharge smear for the presence of Candida species
12
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Description
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Vaginal discharge culture
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Timepoint
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Before the intervention and 2 weeks after the intervention
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Method of measurement
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Assessment of the vaginal discharge culture result on CHROMagar candida medium
13
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Description
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Side effects
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Timepoint
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2 weeks after the intervention
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Method of measurement
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Patient history taking
14
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Description
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Clinical recurrence
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Timepoint
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4 weeks after the intervention
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Method of measurement
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Telephone follow-up at the second follow-up visit to assess the recurrence of specific symptoms of vulvovaginal candidiasis in patients who had achieved a complete clinical cure of the signs and symptoms of vulvovaginal candidiasis at the first follow-up visit.
Intervention groups
1
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Description
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Intervention group: In the intervention group, patients are provided with the necessary hygiene instructions at the time of medication administration. These instructions include wearing cotton underwear and changing it regularly (at least once every 1–2 days), washing the perineal area from front to back and drying it after washing, and washing the hands before and after applying the medication. All participants in the intervention group are instructed to use one full applicator (5 g) of 0.2% oregano essential oil vaginal cream (prepared at the Medicinal Plants Research Center, Tehran University of Medical Sciences) every night for one week and to refrain from using other vaginal medications, antibiotics, and unprotected sexual intercourse during the treatment period. Patients are asked to attend the clinic one week after completion of the treatment course (first follow-up; equivalent to two weeks after the intervention) for post-treatment follow-up. In patients in whom all signs and symptoms of the infection have resolved at the first follow-up, a telephone follow-up is conducted three weeks after completion of the treatment course (second follow-up; equivalent to four weeks after the intervention) to assess clinical recurrence, and the clinical symptoms of infection are assessed by telephone.
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Category
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Treatment - Drugs
2
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Description
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Control group: In the control group, patients will be provided with the necessary hygiene instructions at the time of medication administration. These instructions include wearing cotton underwear and changing it regularly (at least once every 1–2 days), washing the perineal area from front to back and drying it after washing, and washing the hands before and after applying the medication. All participants in the control group will be instructed to use one full applicator (5 g) of 1% clotrimazole vaginal cream (manufactured by Pars Darou Company) every night for one week and to refrain from using other vaginal medications, antibiotics, and unprotected sexual intercourse during the treatment period. Patients will be asked to attend the clinic one week after completion of the treatment course (first follow-up; equivalent to two weeks after the intervention) for post-treatment follow-up. In patients in whom all signs and symptoms of the infection have resolved at the first follow-up, a telephone follow-up will be conducted three weeks after completion of the treatment course (second follow-up; equivalent to four weeks after the intervention) to assess clinical recurrence, and the clinical symptoms of infection will be assessed by telephone.
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Ahvaz University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Not applicable
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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No - There is not a plan to make this available
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Data Dictionary
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No - There is not a plan to make this available
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Title and more details about the data/document
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The data will be available for publication after the completion of the thesis and the publication of the article.
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When the data will become available and for how long
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One week after the completion of the thesis and the publication of the article.
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To whom data/document is available
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Ahvaz Jundishapur University of Medical Sciences and all researchers in hospitals, clinics and universities.
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Under which criteria data/document could be used
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The data will be accessible to others after analysis, through publication in scientific research journals.
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From where data/document is obtainable
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Fatemeh Shahriari, email: fatemeh.shah9675@gmail.com
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What processes are involved for a request to access data/document
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Requests can be sent via email, and a response will be provided within a maximum of one week to 10 days.
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Comments
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