Clotrimazole Vaginal Tablet vs Fluconazole for Severe Vulvovaginal Candidiasis

• Sponsor: Peking University Shenzhen Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02180828
• Collaborator: Bayer (Industry)
• Enrollment: 240
• Location: 1
• Arms: 2
• Duration (Months): 14
• Patients Per Site Per Month: 17.1

Study Details

Study Description

Brief Summary

The study is focused to prove that the efficacy and safety of Clotrimazole vaginal tablet vs Fluconazole for the treatment of severe vulvovaginal candidiasis

Condition or Disease	Intervention/Treatment	Phase
Candidiasis, Vulvovaginal	Drug: Clotrimazole vaginal tablet; Drug: Fluconazole	Phase 4

Detailed Description

The current study is evaluating both the efficacy and safety of the 2 doses of 500 mg clotrimazole vaginal tablet administered intravaginally( at day 1 and day 4) v.s 2 doses of 150 mg fluconazole( at day 1 and day 4) for treatment of severe vulvovaginal candidiasis.The number of participants with adverse events as a measure of safety and tolerability.

Study Design

• Study Type: Interventional
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Case-controlled Randomized Study to the Efficacy of Clotrimazole Vaginal Tablet vs Fluconazole for Severe Vulvovaginal Candidiasis
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clotrimazole vaginal tablet 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	Drug: Clotrimazole vaginal tablet; 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4); Other Names: Canesten
Active Comparator: Fluconazole 2 doses of 150 mg oral Fluconazole (at day1 and day4)	Drug: Fluconazole; 2 doses of 150 mg oral Fluconazole (at day1 and day4); Other Names: Diflucan

Outcome Measures

Primary Outcome Measures

1. Therapeutic Efficacy 1 [7-14 days after treatment (=visit 2)]

   The clinical cure rates of clotrimazole and fluconazol: Clinical cure was defined as the resolution of symptoms present at baseline with a total severity score of ≤2. Improvement was defined as considerable reduction in the severity of baseline signs and symptoms with a decrease in the total score by ≥50%.Patients not clinically cured or showing improvement were considered clinical failures.

2. Therapeutic Efficacy 2 [at days 30-35 follow-up]

   The clinical cure rates of clotrimazole and fluconazol

3. Therapeutic Efficacy 3 [at days 7-14 follow-up]

   Mycological cure of clotrimazole group and fluconazole group

4. Therapeutic Efficacy 4 [at days30-35 follow-up]

   Mycological cure of clotrimazole group and fluconazole group: Mycological cure or failure was referred to as Candida negative or positive,respectively, on Candida culture at follow-up visits.

Secondary Outcome Measures

1. Adverse Events 1 [at day 7-14 follow up]

   Systemic: weak, palpitation, tachycardia, migraine, headache, dizzy, rhinorrhea, numb, dizziness, fatigue.

2. Adverse Events 2 [at day 7-14 follow up]

   Vulvovaginal pruritus, burning, irritation, and bleeding

3. Adverse Events 3 [at day 7-14 follow up]

   Gastrointestinal tract: abdominal pain, diarrhoea, nausea

4. Adverse Events 4 [at day 7-14 follow up]

   Skin sensitivity, urticaria rash, erythematous rash, irritation

5. Total Adverse Events [at day 7-14 follow up]

   Total adverse events(cases)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 48 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Vulvovaginal candidiasis infection is diagnosed, the symptoms evaluated using a numerical rating system based on severity (absent=0; mild=1; moderate=2; severe=3) with a minimum VVC Composite Signs/Symptoms score of 7

2. Subject completes the informed consent process

3. Subject agrees to take study medication when scheduled

4. Subject complies with all clinical trial instructions. Commits to all follow-up visits

Exclusion Criteria:

1. had any other sexually transmitted disease or gynaecological abnormality requiring treatment

2. had a disease known to predispose to candidiasis such as diabetes mellitus, or were receiving antibiotics or corticosteriods

3. were pregnant

4. had used antifungal medication in the week before entry

5. were expected to menstruate within seven days of the start of treatment

6. infected more than one candida species

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University Shenzhen Hospital	Shenzhen	Guangdong	China	518036

Sponsors and Collaborators

• Peking University Shenzhen Hospital
• Bayer

Investigators

• Principal Investigator: Shangrong Fan, M.D., Peking University Shenzhen Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis

Publications

None provided.

• Responsible Party: Shangrong Fan, Prof of Dept of Obstetrics and Gynecology, Peking University Shenzhen Hospital
• ClinicalTrials.gov Identifier: NCT02180828
• Other Study ID Numbers: pkuszh-2014-02
• First Posted: Jul 3, 2014
• Last Update Posted: May 2, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Candidiasis; Candidiasis, Vulvovaginal; Fluconazole; Clotrimazole; Miconazole

Study Results

Participant Flow

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Period Title: Overall Study
STARTED	120	120
COMPLETED	115	113
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole	Total
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)	Total of all reporting groups
Overall Participants	120	120	240
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	120 100%	120 100%	240 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29 (6)	29 (7)	29 (7)
Sex: Female, Male (Count of Participants)
Female	120 100%	120 100%	240 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
China	120 100%	120 100%	240 100%

Outcome Measures

1. Primary Outcome

Title	Therapeutic Efficacy 1
Description	The clinical cure rates of clotrimazole and fluconazol: Clinical cure was defined as the resolution of symptoms present at baseline with a total severity score of ≤2. Improvement was defined as considerable reduction in the severity of baseline signs and symptoms with a decrease in the total score by ≥50%.Patients not clinically cured or showing improvement were considered clinical failures.
Time Frame	7-14 days after treatment (=visit 2)

Outcome Measure Data

Analysis Population Description

PPS

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	114	110
Number [participants]	102 85%	98 81.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Yes
Statistical Test of Hypothesis	p-Value	0.925
	Comments
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	Therapeutic Efficacy 2
Description	The clinical cure rates of clotrimazole and fluconazol
Time Frame	at days 30-35 follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	114	109
Number [participants]	82 68.3%	85 70.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Yes
Statistical Test of Hypothesis	p-Value	0.298
	Comments
	Method	Chi-squared
	Comments

3. Primary Outcome

Title	Therapeutic Efficacy 3
Description	Mycological cure of clotrimazole group and fluconazole group
Time Frame	at days 7-14 follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	115	110
Number [participants]	90 75%	81 67.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	90% power and a two-sided alpha level of 0.05
Statistical Test of Hypothesis	p-Value	0.147
	Comments
	Method	Chi-squared
	Comments

4. Primary Outcome

Title	Therapeutic Efficacy 4
Description	Mycological cure of clotrimazole group and fluconazole group: Mycological cure or failure was referred to as Candida negative or positive,respectively, on Candida culture at follow-up visits.
Time Frame	at days30-35 follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	114	109
Number [participants]	62 51.7%	61 50.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Yes
Statistical Test of Hypothesis	p-Value	0.147
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Adverse Events 1
Description	Systemic: weak, palpitation, tachycardia, migraine, headache, dizzy, rhinorrhea, numb, dizziness, fatigue.
Time Frame	at day 7-14 follow up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	115	113
Number [participants]	1 0.8%	9 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Adverse Events 2
Description	Vulvovaginal pruritus, burning, irritation, and bleeding
Time Frame	at day 7-14 follow up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	115	113
Number [participants]	12 10%	1 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Adverse Events 3
Description	Gastrointestinal tract: abdominal pain, diarrhoea, nausea
Time Frame	at day 7-14 follow up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	115	113
Number [participants]	3 2.5%	3 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.658
	Comments
	Method	Chi-squared
	Comments

8. Secondary Outcome

Title	Adverse Events 4
Description	Skin sensitivity, urticaria rash, erythematous rash, irritation
Time Frame	at day 7-14 follow up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	115	113
Number [participants]	0 0%	3 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.123
	Comments
	Method	Chi-squared
	Comments

9. Secondary Outcome

Title	Total Adverse Events
Description	Total adverse events(cases)
Time Frame	at day 7-14 follow up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clotrimazole Vaginal Tablet	Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)	2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
Measure Participants	115	113
Number [participants]	16 13.3%	12 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clotrimazole Vaginal Tablet, Fluconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.274
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	1 month
Adverse Event Reporting Description	The adverse events of clotrimazole vaginal tablet were mainly local and mild. Most of the adverse events of fluconazole were systemic.
Arm/Group Title	Clotrimazole Vaginal Tablet		Fluconazole
Arm/Group Description	2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4) Clotrimazole vaginal tablet: 2 doses of 500 mg Clotrimazole administered intravaginally (at day1 and day4)		2 doses of 150 mg oral Fluconazole (at day1 and day4) Fluconazole: 2 doses of 150 mg oral Fluconazole (at day1 and day4)
All Cause Mortality
	Clotrimazole Vaginal Tablet		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Clotrimazole Vaginal Tablet		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/115 (0%)		0/113 (0%)
Other (Not Including Serious) Adverse Events
	Clotrimazole Vaginal Tablet		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/115 (11.3%)		10/113 (8.8%)
Cardiac disorders
Systemic	1/115 (0.9%)	1	9/113 (8%)	9
Reproductive system and breast disorders
Vulvovaginal	12/115 (10.4%)	12	1/113 (0.9%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.