Trial Outcomes & Findings for Rwanda Vaginal Microbiota Restoration Study (NCT NCT02459665)
NCT ID: NCT02459665
Last Updated: 2019-07-16
Results Overview
Modified Amsel criteria positive is at least 2 of 3 of the following positive: clue cells, vaginal pH, whiff test. Modified intent-to-treat (ITT) analyses (women with Nugent 7-10 at enrollment excluded), using person-years (PY) at risk as denominator of each incidence rate.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
68 participants
Primary outcome timeframe
2 months (intervention period)
Results posted on
2019-07-16
Participant Flow
The target population was women at high risk of urogenital infections living in Kigali, Rwanda. Recruitment activities were implemented by study staff with the help of Community Mobilizers, who were selected due to their strong connections with high-risk women in Kigali. They helped staff organize recruitment meetings in relevant communities.
At the end of the screening process, women were either ineligible or diagnosed with bacterial vaginosis (by modified Amsel criteria and/or Nugent score) and/or trichomoniasis (by culture or wet mount) and treated with 500 mg oral metronidazole 2x/day for 7 days. An enrollment visit was scheduled within three days after treatment completion.
Participant milestones
| Measure |
Control
Behavioral counseling only
|
Oral Metronidazole
Oral metronidazole 2-month intermittent use plus counseling
|
Ecologic Femi+
Ecologic Femi+ vaginal probiotic capsule 2-month intermittent use plus counseling
|
Gynophilus LP
Gynophilus LP vaginal probiotic tablet 2-month intermittent use plus counseling
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
17
|
17
|
17
|
17
|
|
Overall Study
Day 7 Visit
|
17
|
17
|
17
|
16
|
|
Overall Study
Month 1 Visit
|
17
|
17
|
17
|
16
|
|
Overall Study
Month 2 Visit
|
17
|
16
|
17
|
16
|
|
Overall Study
Month 6 Visit
|
17
|
16
|
16
|
15
|
|
Overall Study
COMPLETED
|
17
|
16
|
16
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
2
|
Reasons for withdrawal
| Measure |
Control
Behavioral counseling only
|
Oral Metronidazole
Oral metronidazole 2-month intermittent use plus counseling
|
Ecologic Femi+
Ecologic Femi+ vaginal probiotic capsule 2-month intermittent use plus counseling
|
Gynophilus LP
Gynophilus LP vaginal probiotic tablet 2-month intermittent use plus counseling
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
2
|
Baseline Characteristics
Rwanda Vaginal Microbiota Restoration Study
Baseline characteristics by cohort
| Measure |
Control
n=17 Participants
Behavioral counseling only
|
Oral Metronidazole
n=17 Participants
Oral metronidazole 2-month intermittent use plus counseling
|
Ecologic Femi+
n=17 Participants
Ecologic Femi+ vaginal probiotic capsule 2-month intermittent use plus counseling
|
Gynophilus LP
n=17 Participants
Gynophilus LP vaginal probiotic tablet 2-month intermittent use plus counseling
|
Total
n=68 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
68 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Continuous
|
29 years
n=5 Participants
|
30 years
n=7 Participants
|
33 years
n=5 Participants
|
31 years
n=4 Participants
|
31 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
68 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
African (Rwandan)
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
68 Participants
n=21 Participants
|
|
Region of Enrollment
Rwanda
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
68 Participants
n=21 Participants
|
|
Exchanged sex for money/goods in past month
|
17 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
63 Participants
n=21 Participants
|
|
Sex partners in the past month
|
5 sex partners
n=5 Participants
|
5 sex partners
n=7 Participants
|
3 sex partners
n=5 Participants
|
3 sex partners
n=4 Participants
|
5 sex partners
n=21 Participants
|
PRIMARY outcome
Timeframe: 2 months (intervention period)Population: Modified ITT population: all randomized women except women with Nugent 7-10 at enrollment.
Modified Amsel criteria positive is at least 2 of 3 of the following positive: clue cells, vaginal pH, whiff test. Modified intent-to-treat (ITT) analyses (women with Nugent 7-10 at enrollment excluded), using person-years (PY) at risk as denominator of each incidence rate.
Outcome measures
| Measure |
Control
n=15 Participants
Behavioral counseling only
|
Oral Metronidazole
n=11 Participants
Oral metronidazole 2-months intermittent use plus counseling
|
Ecologic Femi+
n=14 Participants
Ecologic Femi+ vaginal probiotic capsules 2-months intermittent use plus counseling
|
Gynophilus LP
n=11 Participants
Gynophilus LP vaginal probiotic tablets 2-months intermittent use plus counseling
|
|---|---|---|---|---|
|
Bacterial Vaginosis (BV) Incidence by Modified Amsel Criteria
|
7.53 Incidence: events per PY at risk
Interval 4.28 to 13.26
|
2.04 Incidence: events per PY at risk
Interval 0.66 to 6.31
|
3.36 Incidence: events per PY at risk
Interval 1.51 to 7.48
|
3.35 Incidence: events per PY at risk
Interval 1.26 to 8.92
|
PRIMARY outcome
Timeframe: 2 months (intervention period)Population: Modified ITT population: All randomized women except women with Nugent 7-10 at enrollment.
The Nugent score is a scale from 0-10 based on visualisation of three different bacterial morphotypes on a Gram stained slide, but in the incidence rates, the variable was used as a binary variable: BV present (Nugent score 7-10) or absent (Nugent score 0-6). Modified intent-to-treat (ITT) analyses (women with Nugent 7-10 at enrollment excluded), using person-years (PY) at risk as the denominator for each incidence rate.
Outcome measures
| Measure |
Control
n=15 Participants
Behavioral counseling only
|
Oral Metronidazole
n=11 Participants
Oral metronidazole 2-months intermittent use plus counseling
|
Ecologic Femi+
n=14 Participants
Ecologic Femi+ vaginal probiotic capsules 2-months intermittent use plus counseling
|
Gynophilus LP
n=11 Participants
Gynophilus LP vaginal probiotic tablets 2-months intermittent use plus counseling
|
|---|---|---|---|---|
|
Bacterial Vaginosis (BV) Incidence by Nugent Scoring (Nugent 7-10)
|
10.18 Incidence: events per PY at risk
Interval 5.48 to 18.92
|
1.41 Incidence: events per PY at risk
Interval 0.35 to 5.62
|
3.58 Incidence: events per PY at risk
Interval 1.61 to 7.96
|
5.36 Incidence: events per PY at risk
Interval 2.41 to 11.93
|
PRIMARY outcome
Timeframe: 2 months (intervention period)Population: All randomized women except one woman in the Gynophilus LP group who withdrew immediately after enrollment.
A swab was inoculated into an InPouch culture pouch, specifically designed for TV growth. The pouch was checked daily for five days to detect growth. The results was positive when growth detected and negative when no growth detected on the fifth day. Intent-to-treat (ITT) analyses, using person-years (PY) at risk as the denominator for each incidence rate.
Outcome measures
| Measure |
Control
n=17 Participants
Behavioral counseling only
|
Oral Metronidazole
n=17 Participants
Oral metronidazole 2-months intermittent use plus counseling
|
Ecologic Femi+
n=17 Participants
Ecologic Femi+ vaginal probiotic capsules 2-months intermittent use plus counseling
|
Gynophilus LP
n=16 Participants
Gynophilus LP vaginal probiotic tablets 2-months intermittent use plus counseling
|
|---|---|---|---|---|
|
Trichomonas Vaginalis (TV) Incidence by Culture
|
1.10 Incidence: events per PY at risk
Interval 0.35 to 3.41
|
0 Incidence: events per PY at risk
Interval 0.0 to 0.0
|
0 Incidence: events per PY at risk
Interval 0.0 to 0.0
|
0 Incidence: events per PY at risk
Interval 0.0 to 0.0
|
PRIMARY outcome
Timeframe: 6 months: 2 months intervention period plus 4 months after intervention cessationPopulation: All randomized women except one woman in the Gynophilus LP group who withdrew immediately after enrollment.
A wet mount is a smear of vaginal fluid on a microscopy slide, which is examined under a microscope. Yeasts are visible without staining. The definition of vaginal candidiasis was any yeast visible on the wet mount. Symptomatic vaginal candidiasis was considered a safety outcome because treatment of bacterial vaginosis often results in vaginal candidiasis. Intent-to-treat (ITT) analysis with person-years (PY) at risk as the denominator of all incidence rates.
Outcome measures
| Measure |
Control
n=17 Participants
Behavioral counseling only
|
Oral Metronidazole
n=17 Participants
Oral metronidazole 2-months intermittent use plus counseling
|
Ecologic Femi+
n=17 Participants
Ecologic Femi+ vaginal probiotic capsules 2-months intermittent use plus counseling
|
Gynophilus LP
n=16 Participants
Gynophilus LP vaginal probiotic tablets 2-months intermittent use plus counseling
|
|---|---|---|---|---|
|
Vaginal Candidiasis Incidence by Wet Mount Microscopy
|
0 Incidence: events per PY at risk
Interval 0.0 to 0.0
|
0 Incidence: events per PY at risk
Interval 0.0 to 0.0
|
0 Incidence: events per PY at risk
Interval 0.0 to 0.0
|
0 Incidence: events per PY at risk
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 2 months (intervention period)Population: All randomized women except for one woman in Gynophilus LP who withdrew immediately after enrollment, using lactobacillus concentration in log10 copies per microliter at the M2 visit (at the time of intervention cessation).
The vaginal microbiota sequencing results are exploratory and full data can be found in a manuscript on the BioRxiv preprint server. The most important outcome is the concentration of Lactobacillus genus in vaginal samples taken at the end of the intervention period (M2 visit).
Outcome measures
| Measure |
Control
n=17 Participants
Behavioral counseling only
|
Oral Metronidazole
n=17 Participants
Oral metronidazole 2-months intermittent use plus counseling
|
Ecologic Femi+
n=17 Participants
Ecologic Femi+ vaginal probiotic capsules 2-months intermittent use plus counseling
|
Gynophilus LP
n=16 Participants
Gynophilus LP vaginal probiotic tablets 2-months intermittent use plus counseling
|
|---|---|---|---|---|
|
Vaginal Microbiota Composition by Illumina HiSeq Sequencing: Lactobacillus Genus Concentration
|
3.86 Lactobacillus log10 copies/microliter
Interval 2.53 to 5.19
|
5.21 Lactobacillus log10 copies/microliter
Interval 4.27 to 6.14
|
5.30 Lactobacillus log10 copies/microliter
Interval 4.97 to 5.63
|
4.68 Lactobacillus log10 copies/microliter
Interval 3.55 to 5.81
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 months (intervention period)Population: Adherence data are available for all randomized women except one woman in the Gynophilus LP group who withdrew immediately after enrollment. Acceptability data are available for all women randomized to the two vaginal probiotics groups except two women in the Gynophilus LP group (another woman withdrew prior to the Month 2 visit).
Full results have been submitted for publication. Adherence was measured at D7, M1, and M2 visits, and a summary measure over the entire period was calculated (available for women using oral metronidazole, Ecologic Femi+, or Gynophilus LP). After the 2-month intervention period, women using vaginal probiotics (Ecologic Femi+ or Gynophilus LP) were asked structured questions about their experiences with product use.
Outcome measures
| Measure |
Control
n=17 Participants
Behavioral counseling only
|
Oral Metronidazole
n=17 Participants
Oral metronidazole 2-months intermittent use plus counseling
|
Ecologic Femi+
n=16 Participants
Ecologic Femi+ vaginal probiotic capsules 2-months intermittent use plus counseling
|
Gynophilus LP
Gynophilus LP vaginal probiotic tablets 2-months intermittent use plus counseling
|
|---|---|---|---|---|
|
Feasibility/Acceptability of Vaginal Probiotic Use by Structured Face-to-face Interview
Overall adherence ≥90%
|
14 Participants
|
15 Participants
|
11 Participants
|
—
|
|
Feasibility/Acceptability of Vaginal Probiotic Use by Structured Face-to-face Interview
Overall adherence ≥80%
|
15 Participants
|
17 Participants
|
13 Participants
|
—
|
|
Feasibility/Acceptability of Vaginal Probiotic Use by Structured Face-to-face Interview
Probiotic insertion as "very comfortable"
|
—
|
17 Participants
|
15 Participants
|
—
|
|
Feasibility/Acceptability of Vaginal Probiotic Use by Structured Face-to-face Interview
Perfect (100%) overall adherence
|
12 Participants
|
10 Participants
|
8 Participants
|
—
|
|
Feasibility/Acceptability of Vaginal Probiotic Use by Structured Face-to-face Interview
Probiotic insertion became easier over time
|
—
|
17 Participants
|
15 Participants
|
—
|
Adverse Events
Control
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Oral Metronidazole
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Ecologic Femi+
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Gynophilus LP
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Control
n=17 participants at risk
Behavioral counseling only
|
Oral Metronidazole
n=17 participants at risk
Oral metronidazole 2-months intermittent use plus counseling
|
Ecologic Femi+
n=17 participants at risk
Ecologic Femi+ vaginal probiotic capsules 2-months intermittent use plus counseling
|
Gynophilus LP
n=17 participants at risk
Gynophilus LP vaginal probiotic tablets 2-months intermittent use plus counseling
|
|---|---|---|---|---|
|
Infections and infestations
Typhoid fever
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
|
Infections and infestations
Malaria during pregnancy
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
Other adverse events
| Measure |
Control
n=17 participants at risk
Behavioral counseling only
|
Oral Metronidazole
n=17 participants at risk
Oral metronidazole 2-months intermittent use plus counseling
|
Ecologic Femi+
n=17 participants at risk
Ecologic Femi+ vaginal probiotic capsules 2-months intermittent use plus counseling
|
Gynophilus LP
n=17 participants at risk
Gynophilus LP vaginal probiotic tablets 2-months intermittent use plus counseling
|
|---|---|---|---|---|
|
Renal and urinary disorders
Burning when passing urine
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
|
Reproductive system and breast disorders
Genital burning
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
11.8%
2/17 • Number of events 2 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
|
Reproductive system and breast disorders
Genital itching
|
11.8%
2/17 • Number of events 2 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
11.8%
2/17 • Number of events 2 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
11.8%
2/17 • Number of events 2 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
11.8%
2/17 • Number of events 2 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
|
Reproductive system and breast disorders
Pain during sex
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
11.8%
2/17 • Number of events 2 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
|
General disorders
Lower abdominal pain
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
|
Reproductive system and breast disorders
Unusual vaginal discharge
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
|
Reproductive system and breast disorders
Sores in the genital and/or anal area
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
0.00%
0/17 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
5.9%
1/17 • Number of events 1 • 6 months: during the 2-month intervention period and up to 4 months after intervention cessation
The definition of adverse events does not differ from the clinicaltrials.gov definitions.
|
Additional Information
Prof. Janneke van de Wijgert, Chief Investigator
University of Liverpool
Phone: +447557195108
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place