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    Clinical Trial Results:
    Chlorhexidine gluconate as treatment and prophylaxis of vulvovaginal Candidiasis

    Summary
    EudraCT number
    		 2020-000758-81
    Trial protocol
    		 SE  
    Global end of trial date
    27 Nov 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Nov 2025
    First version publication date
    07 Nov 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    Chlorhex-KKDS-2021
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05059145
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Karolinska Institutet
    Sponsor organisation address
    Nobels väg 6, Solna, Sweden, 17177
    Public contact
    Nina Bohm-Starke, Karolinska Institutet, Danderyd Hospital. Div of Obstetrics and Gynecology, +46 812355000, nina.bohm-starke@ki.se
    Scientific contact
    Nina Bohm-Starke, Karolinska Institutet, Danderyd Hospital. Div of Obstetrics and Gynecology, +46 812355000, nina.bohm-starke@ki.se
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Jun 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Nov 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Nov 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To analyze if daily vaginal application of 8 ml of Hibitane® for one week and thereafter once a week for another 11 consecutive weeks is at least as effective as fluconazole 150 mg capsules every third day for the first three doses and thereafter 150 mg once a week for another 11 consecutive weeks regarding treatment- and prophylactic efficacy for recurrent vulvovaginal Candida albicans infection.
    Protection of trial subjects
    The first ethical approval on the clinical trial was granted by the Swedish Ethical Review Authority on September 8, 2020 (Dnr 2020-04035) and the second application including more advanced molecular analyses was granted on February 6, 2022 (Dnr 2021-06538-02). All participants provided written informed consent prior to enrollment.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Apr 2022
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Sweden: 23
    Worldwide total number of subjects
    23
    EEA total number of subjects
    23
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    23
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Recruitment (began April 27, 2022) was conducted via advertisements at regional gynecological clinics and on social media, inviting women with RVVC to contact the research midwife at the Women’s Department at Danderyd Hospital for further information. Women meeting the age and symptom criteria were invited to a screening visit.

    Pre-assignment
    Screening details
    		 Inclusion criteria: women aged 18-50y with a history of RVVC (≥ 3 episodes of Candida infection in the past year); current symptoms consistent with acute vulvovaginal candidiasis; culture-confirmed C. albicans susceptible to FLZ.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Chlorhexidine gluconate (Hibitane®)
    Arm description
    		 The CHG group received Hibitane® 1% vaginal cream, 7.5 mL nightly for 7 days as acute treatment, followed by prophylactic treatment with 7.5 mL once weekly for 11 consecutive weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hibitane
    Investigational medicinal product code
    SUB01215MIG
    Other name
    CHLORHEXIDINE GLUCONATE
    Pharmaceutical forms
    Vaginal cream
    Routes of administration
    Vaginal use
    Dosage and administration details
    Daily vaginal application of 8 ml of Hibitane® for one week and thereafter once a week for another 11 consecutive weeks.

    Arm title
    		 Fluconazole®
    Arm description
    		 The FLZ group received oral capsules Fluconazole® 150 mg every third day for the first three doses (acute phase), followed by 150 mg once weekly for 11 consecutive weeks (prophylactic phase).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fluconazole
    Investigational medicinal product code
    SUB07674MIG
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Fluconazole 150 mg capsules every third day for the first three doses and thereafter 150 mg once a week for another 11 consecutive weeks.

    Number of subjects in period 1
    		Chlorhexidine gluconate (Hibitane®) Fluconazole®
    Started
    12
    11
    Completed
    5
    11
    Not completed
    7
    0
         Adverse event, non-fatal
    7
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Chlorhexidine gluconate (Hibitane®)
    Reporting group description
    		 The CHG group received Hibitane® 1% vaginal cream, 7.5 mL nightly for 7 days as acute treatment, followed by prophylactic treatment with 7.5 mL once weekly for 11 consecutive weeks.

    Reporting group title
    Fluconazole®
    Reporting group description
    		 The FLZ group received oral capsules Fluconazole® 150 mg every third day for the first three doses (acute phase), followed by 150 mg once weekly for 11 consecutive weeks (prophylactic phase).

    Reporting group values
    		 Chlorhexidine gluconate (Hibitane®) Fluconazole® Total
    Number of subjects
    		 12 11 23
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 33 (24 to 46) 32 (23 to 45) -
    Gender categorical
    Units: Subjects
        Female
    		 12 11 23
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Chlorhexidine gluconate (Hibitane®)
    Reporting group description
    		 The CHG group received Hibitane® 1% vaginal cream, 7.5 mL nightly for 7 days as acute treatment, followed by prophylactic treatment with 7.5 mL once weekly for 11 consecutive weeks.

    Reporting group title
    Fluconazole®
    Reporting group description
    		 The FLZ group received oral capsules Fluconazole® 150 mg every third day for the first three doses (acute phase), followed by 150 mg once weekly for 11 consecutive weeks (prophylactic phase).

    Subject analysis set title
    Chlorhexidine gluconate (Hibitane®) after 1 week
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    7 participants in the CHG group chose to withdraw from the study due to local pain and discomfort, and did not attend the planned visits at 3 months (end of prophylactic treatment) and 6 months (follow-up visit). Therefore, this primary result will only present end points for the first follow-up 1 week after acute treatment where we have results from all 11 in the CHG-group.

    Primary: The proportion of women in each group that has cleared the infection after 1week of treatment

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    End point title
    		 The proportion of women in each group that has cleared the infection after 1week of treatment [1]
    End point description
    The early termination of the study with less than 50% of the planned number of participants (30+30 in each study arm) has impact on the interpretation of the results. However, the primary outcome of negative candida cultures after one week of treatment for an acute episode of vulvovaginal candidiasis showed an equal response in both study groups. This preliminary result indicates that chlorhexidine could be an effective alternative treatment for recurrent vulvovaginal candidiasis, but the drug in this study (Hibitane®) cannot be used, which will be the preliminary conclusion of the study.
    End point type
    Primary
    End point timeframe
    The proportion of women in each group that has cleared the infection after 1week of treatment, defined as negative cultures for Candida albicans.
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: It was planned follow-up visits at 1 week, 3 months and 6 months. But 7 participants in CHG-group withdrew after 1 week of treatment due to adverse events, therefore we cannot report from the 3 and 6 months visits. We chose to only report from the first 1 week visit where all the CHG-group attended. However, it is important to present the withdrawal due to adverse events, hence we showed the planned baseline period arm "Chlorhexidine gluconate (Hibitane®)" but cannot do a full report.
    End point values
    		 Fluconazole® Chlorhexidine gluconate (Hibitane®) after 1 week
    Number of subjects analysed
    11
    12
    Units: Number of patients
    12
    9
    Statistical analysis title
    		 The proportion that has cleared infection
    Comparison groups
    Fluconazole® v Chlorhexidine gluconate (Hibitane®) after 1 week
    Number of subjects included in analysis
    23
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.82
    Method
    		 Fisher exact
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events occurred within the acute treatment period (first week of treatment), or during the prophylactic treatment period between week 2 to 3 months after study start.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 n/a
    Dictionary version
    n/a
    Reporting groups
    Reporting group title
    Fluconazole®
    Reporting group description
    		 -

    Reporting group title
    Chlorhexidine gluconate (Hibitane®)
    Reporting group description
    		 -

    Serious adverse events
    		 Fluconazole® Chlorhexidine gluconate (Hibitane®)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 12 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Fluconazole® Chlorhexidine gluconate (Hibitane®)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 11 (27.27%)
    8 / 12 (66.67%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Diarrhoea
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Pain
    Additional description: Local symptoms of pain, discomfort and irritation of the vulva and vagina after the vaginal application of the study drug.
         subjects affected / exposed
    0 / 11 (0.00%)
    8 / 12 (66.67%)
         occurrences all number
    0
    8
    Discomfort
    Additional description: Local symptoms of pain, discomfort and irritation of the vulva and vagina after the vaginal application of the study drug.
         subjects affected / exposed
    0 / 11 (0.00%)
    8 / 12 (66.67%)
         occurrences all number
    0
    8
    Irritability
    Additional description: Local symptoms of pain, discomfort and irritation of the vulva and vagina after the vaginal application of the study drug.
         subjects affected / exposed
    0 / 11 (0.00%)
    8 / 12 (66.67%)
         occurrences all number
    0
    8

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The early termination of the study with less than 50% of the planned number of participants (30+30 in each study arm) has impact on the interpretation of the results.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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