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Trial record 24 of 26 for:    "Vulvovaginal Candidiasis" | "Hormone Antagonists"

Topical Metronidazole and Miconazole Co-formulated Vaginal Suppositories for Preventing Vaginal Infections in HIV-seronegative Women

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ClinicalTrials.gov Identifier: NCT01230814
Recruitment Status : Completed
First Posted : October 29, 2010
Results First Posted : September 26, 2014
Last Update Posted : October 6, 2014
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Bacterial Vaginosis
Candidiasis
Trichomoniasis
Interventions Drug: Neo-Penotran® Forte (active ingredient Metronidazole & Miconazole Nitrate)
Drug: Placebo
Enrollment 234
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Hide Arm/Group Description Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month. Placebo suppositories nightly for five consecutive nights each month.
Period Title: Overall Study
Started 118 116
Completed 105 112
Not Completed 13 4
Reason Not Completed
Lost to Follow-up             11             3
Discontinued (not due to adverse event)             2             1
Arm/Group Title Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo Total
Hide Arm/Group Description Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month. Placebo suppositories nightly for five consecutive nights each month. Total of all reporting groups
Overall Number of Baseline Participants 118 116 234
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 118 participants 116 participants 234 participants
29
(24 to 34)
29
(23 to 35)
29
(24 to 34)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 118 participants 116 participants 234 participants
<=18 years
1
   0.8%
1
   0.9%
2
   0.9%
Between 18 and 65 years
117
  99.2%
115
  99.1%
232
  99.1%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 118 participants 116 participants 234 participants
Female
118
 100.0%
116
 100.0%
234
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 118 participants 116 participants 234 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
118
 100.0%
111
  95.7%
229
  97.9%
White
0
   0.0%
4
   3.4%
4
   1.7%
More than one race
0
   0.0%
1
   0.9%
1
   0.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 118 participants 116 participants 234 participants
Hispanic or Latino
0
   0.0%
1
   0.9%
1
   0.4%
Not Hispanic or Latino
118
 100.0%
115
  99.1%
233
  99.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 118 participants 116 participants 234 participants
United States 29 29 58
Kenya 89 87 176
1.Primary Outcome
Title Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing Vulvovaginal Candidiasis (VVC).
Hide Description Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for VVC based on the presence of fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet mount plus a positive culture showing yeast on Sabouraud’s agar.
Time Frame Months 2, 4, 6, 8, 10, and 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population which consisted of all women who were randomized and had at least one follow-up visit. Two women in the metronidazole with miconazole arm did not return after enrollment.
Arm/Group Title Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Hide Arm/Group Description:
Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month.
Placebo suppositories nightly for five consecutive nights each month.
Overall Number of Participants Analyzed 116 116
Overall Number of Units Analyzed
Type of Units Analyzed: Follow-up visits
645 665
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of follow-up visits
10.4
(8.2 to 13.2)
11.3
(9.0 to 14.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1: Metronidazole Plus Miconazole, Arm 2: Placebo
Comments Each participant within a study arm was considered a cluster, with observations at a maximum of 6 visits. The percentage of visits at which VVC was detected was compared between metronidazole plus miconazole arm versus placebo arm using a chi-squared statistic adjusted for clustering using the method of Donner and Klar (2000).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.690
Comments The a priori threshold for statistical significance for VVC was p<0.020 (two-sided).
Method Clustered chi-squared statistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.62 to 1.37
Estimation Comments For the relative risk estimate, the metronidazole plus miconazole arm represented the numerator and the placebo arm represented the denominator such that a relative risk <1 indicates a lower percentage of positive test visits in the treated arm.
2.Primary Outcome
Title Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing Bacterial Vaginosis (BV).
Hide Description Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for BV as determined by applying standard microscopic scoring criteria (Nugent’s criteria) to vaginal Gram stained slides. BV is diagnosed when the score is greater than or equal to 7.
Time Frame Months 2, 4, 6, 8, 10, and 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population which consisted of all women who were randomized and had at least one follow-up visit. Two women in the metronidazole with miconazole arm did not return after enrollment.
Arm/Group Title Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Hide Arm/Group Description:
Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month.
Placebo suppositories nightly for five consecutive nights each month.
Overall Number of Participants Analyzed 116 116
Overall Number of Units Analyzed
Type of Units Analyzed: Follow-up Visits
645 665
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of follow-up visits
21.2
(18.0 to 25.1)
32.5
(28.4 to 37.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1: Metronidazole Plus Miconazole, Arm 2: Placebo
Comments Each participant within a study arm was considered a cluster, with observations at a maximum of 6 visits. The percentage of visits at which BV was detected was compared between metronidazole plus miconazole arm versus placebo arm using a chi-squared statistic adjusted for clustering using the method of Donner and Klar (2000).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments The a priori threshold for statistical significance for BV was p<0.030 (two-sided).
Method clutstered chi-squared statistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.48 to 0.87
Estimation Comments For the relative risk estimate, the metronidazole plus miconazole arm represented the numerator and the placebo arm represented the denominator such that a relative risk <1 indicates a lower percentage of test visits in the treated arm.
3.Secondary Outcome
Title Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Placebo for Preventing Any Vaginal Infection (a Combined Endpoint Including BV, VVC, and Trichomonas Vaginalis Infection).
Hide Description Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for any of three vaginal infections (BV, VVC, Trichomonas vaginalis infection).
Time Frame Months 2, 4, 6, 8, 10, and 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population which consisted of all women who were randomized and had at least one follow-up visit. Two women in the metronidazole with miconazole arm did not return after enrollment.
Arm/Group Title Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Hide Arm/Group Description:
Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month.
Placebo suppositories nightly for five consecutive nights each month.
Overall Number of Participants Analyzed 116 116
Overall Number of Units Analyzed
Type of Units Analyzed: Follow-up visits
645 665
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of follow-up visits
32.6
(28.4 to 37.3)
46.5
(41.6 to 51.9)
4.Secondary Outcome
Title Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing BV by Clinical Criteria (Amsel’s Criteria).
Hide Description Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for BV by clinical criteria (Amsel's criteria).
Time Frame Months 2, 4, 6, 8, 10, and 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population which consisted of all women who were randomized and had at least one follow-up visit. Two women in the metronidazole with miconazole arm did not return after enrollment.
Arm/Group Title Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Hide Arm/Group Description:
Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month.
Placebo suppositories nightly for five consecutive nights each month.
Overall Number of Participants Analyzed 116 116
Overall Number of Units Analyzed
Type of Units Analyzed: Follow-up visits
645 665
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of follow-up visits
14.4
(11.8 to 17.7)
18.2
(15.2 to 21.7)
Time Frame Months 2, 4, 6, 8, 10, and 12, and any interim visits.
Adverse Event Reporting Description Adverse events were followed until resolution even beyond the study-reporting period. Resolution of an adverse event is defined as the return to pretreatment status or stabilization of the condition with the expectation that it will remain chronic.
 
Arm/Group Title Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Hide Arm/Group Description Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month. Placebo suppositories nightly for five consecutive nights each month.
All-Cause Mortality
Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/116 (2.59%)      1/116 (0.86%)    
Infections and infestations     
Malaria * 1  1/116 (0.86%)  1 0/116 (0.00%)  0
Typhoid fever * 1  1/116 (0.86%)  1 0/116 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Soft tissue injury * 1  1/116 (0.86%)  1 0/116 (0.00%)  0
Pelvic fracture * 1  0/116 (0.00%)  0 1/116 (0.86%)  1
Pregnancy, puerperium and perinatal conditions     
Ruptured ectopic pregnancy * 1  1/116 (0.86%)  1 0/116 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm 1: Metronidazole Plus Miconazole Arm 2: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   109/116 (93.97%)      111/116 (95.69%)    
Cardiac disorders     
Chest pain * 1  8/116 (6.90%)  9 7/116 (6.03%)  8
Gastrointestinal disorders     
Abdominal pain * 1  8/116 (6.90%)  10 17/116 (14.66%)  21
Abdominal pain lower * 1  14/116 (12.07%)  17 9/116 (7.76%)  12
Dyspepsia * 1  10/116 (8.62%)  13 13/116 (11.21%)  17
Gastroenteritis * 1  9/116 (7.76%)  10 7/116 (6.03%)  7
Nausea * 1  5/116 (4.31%)  6 7/116 (6.03%)  9
Toothache * 1  8/116 (6.90%)  9 8/116 (6.90%)  10
Infections and infestations     
Body tinea * 1  8/116 (6.90%)  8 8/116 (6.90%)  10
Malaria * 1  7/116 (6.03%)  10 9/116 (7.76%)  11
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  10/116 (8.62%)  11 9/116 (7.76%)  12
Back pain * 1  21/116 (18.10%)  25 11/116 (9.48%)  13
Myalgia * 1  7/116 (6.03%)  7 10/116 (8.62%)  15
Soft tissue injury * 1  8/116 (6.90%)  9 4/116 (3.45%)  5
Nervous system disorders     
Headache * 1  24/116 (20.69%)  31 36/116 (31.03%)  53
Hypoaesthesia * 1  12/116 (10.34%)  17 12/116 (10.34%)  19
Renal and urinary disorders     
Urinary tract infection * 1  14/116 (12.07%)  24 12/116 (10.34%)  13
Reproductive system and breast disorders     
Menorrhagia * 1  9/116 (7.76%)  9 8/116 (6.90%)  8
Nasopharyngitis * 1  6/116 (5.17%)  11 7/116 (6.03%)  9
Vaginal discharge * 1  27/116 (23.28%)  55 43/116 (37.07%)  67
Vaginal odour * 1  10/116 (8.62%)  19 5/116 (4.31%)  11
Vulvovaginal discomfort * 1  8/116 (6.90%)  13 6/116 (5.17%)  9
Vulvovaginal pruritus * 1  38/116 (32.76%)  62 44/116 (37.93%)  78
Vulvovaginitis * 1  19/116 (16.38%)  23 19/116 (16.38%)  27
Respiratory, thoracic and mediastinal disorders     
Cough * 1  6/116 (5.17%)  8 12/116 (10.34%)  16
Pharyngitis * 1  6/116 (5.17%)  7 7/116 (6.03%)  9
Respiratory tract infection * 1  14/116 (12.07%)  14 18/116 (15.52%)  24
Rhinitis * 1  14/116 (12.07%)  16 10/116 (8.62%)  11
Tonsillitis * 1  9/116 (7.76%)  9 8/116 (6.90%)  9
Upper respiratory tract infection * 1  40/116 (34.48%)  64 36/116 (31.03%)  54
Skin and subcutaneous tissue disorders     
Rash * 1  7/116 (6.03%)  7 7/116 (6.03%)  8
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Shelly Lensing, MS
Organization: University of Arkansas for Medical Sciences
Phone: 501-686-8203
EMail: sylensing@uams.edu
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01230814     History of Changes
Other Study ID Numbers: 09-0070
DMID STI CTG 09-0070 PVI
First Submitted: October 28, 2010
First Posted: October 29, 2010
Results First Submitted: August 14, 2014
Results First Posted: September 26, 2014
Last Update Posted: October 6, 2014