NCT02459665

Brief Summary

A pilot randomized controlled clinical trial of intermittent use of two different vaginal lactobacilli-containing probiotics, and oral metronidazole, to prevent bacterial vaginosis recurrence.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
68

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Jun 2015

Typical duration for not_applicable

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 21, 2015

Completed
12 days until next milestone

First Posted

Study publicly available on registry

June 2, 2015

Completed
3 days until next milestone

Study Start

First participant enrolled

June 5, 2015

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 23, 2016

Completed
2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 6, 2018

Completed
11 months until next milestone

Results Posted

Study results publicly available

July 16, 2019

Completed
Last Updated

July 16, 2019

Status Verified

June 1, 2019

Enrollment Period

9 months

First QC Date

May 21, 2015

Results QC Date

April 26, 2019

Last Update Submit

June 21, 2019

Conditions

Bacterial Vaginosis

Outcome Measures

Primary Outcomes (4)

  • Bacterial Vaginosis (BV) Incidence by Modified Amsel Criteria

    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.

    2 months (intervention period)

  • Bacterial Vaginosis (BV) Incidence by Nugent Scoring (Nugent 7-10)

    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.

    2 months (intervention period)

  • Trichomonas Vaginalis (TV) Incidence by Culture

    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.

    2 months (intervention period)

  • Vaginal Candidiasis Incidence by Wet Mount Microscopy

    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.

    6 months: 2 months intervention period plus 4 months after intervention cessation

Secondary Outcomes (1)

  • Vaginal Microbiota Composition by Illumina HiSeq Sequencing: Lactobacillus Genus Concentration

    2 months (intervention period)

Other Outcomes (1)

  • Feasibility/Acceptability of Vaginal Probiotic Use by Structured Face-to-face Interview

    2 months (intervention period)

Study Arms (4)

Group 1

NO INTERVENTION

Negative control group: After initial treatment for BV/TV, no intervention.

Group 2

OTHER

Positive control group: After initial treatment for BV/TV, metronidazole pills (500 mg) twice per week for 2 months.

Drug: Prophylactic use of metronidazole pills (500 mg)

Group 3

ACTIVE COMPARATOR

After initial treatment for BV/TV, Ecologic Femi+ vaginal capsule (a vaginal probiotic) once per day for 5 days immediately after the initial treatment followed by thrice weekly for two months.

Biological: Vaginal multiple lactobacilli-containing probiotic for prevention of BV recurrence

Group 4

ACTIVE COMPARATOR

After initial treatment for BV/TV, Gynophilus LP vaginal tablet (a vaginal probiotic) once every 4 days for two months.

Biological: Vaginal Lcr35-containing probiotic for prevention of BV recurrence

Interventions

Vaginal multiple lactobacilli-containing probiotic for prevention of BV recurrenceBIOLOGICAL

Vaginal probiotic to restore the vaginal microbiome and prevent BV recurrence after metronidazole treatment for BV or TV

Also known as: Ecologic Femi+ vaginal capsule
Group 3
Prophylactic use of metronidazole pills (500 mg)DRUG

Prophylactic use of metronidazole pills to prevent BV recurrence after metronidazole treatment for BV or TV

Also known as: Tricozole
Group 2
Vaginal Lcr35-containing probiotic for prevention of BV recurrenceBIOLOGICAL

Vaginal probiotic to restore the vaginal microbiome and prevent BV recurrence after metronidazole treatment for BV or TV

Also known as: Gynophilus LP vaginal tablet
Group 4

Eligibility Criteria

Age18 Years - 45 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Sexually active, defined as having had sex at least twice in the two weeks prior to screening
  • At high risk of HIV/STIs/BV, defined as having had more than one sexual partner in the last 12 months OR having been treated for an STI and/or BV in the last 12 months
  • Successfully treated for BV (modified Amsel criteria) or TV (wet mount), and free of STIs, symptomatic vaginal candidiasis and UTI at enrollment
  • Currently in good physical and mental health as judged by a study physician
  • Willing and able to adhere to study procedures and provide written informed consent.

You may not qualify if:

  • Pregnant
  • HIV positive
  • Clinician-observed genital ulcers, condylomata, or other genital abnormalities at screening or enrollment
  • Underwent a gynaecological surgery/invasive procedure in the 3 months prior to screening
  • History of significant urogenital prolapse, undiagnosed vaginal bleeding, urine or faecal incontinence, or blood clotting disorders
  • Allergic to metronidazole or any other components of the study drugs
  • Not willing to stop use of other oral or vaginal probiotics from the screening visit until the end of study participation
  • Participating in another health intervention study
  • For any other reason potentially interfering with participant safety or protocol adherence as judged by the Principal Investigator

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (3)

  • Verwijs MC, Agaba S, Umulisa MM, van de Wijgert JHHM. Feasibility and acceptability of frequent vaginal self-sampling at home by Rwandan women at high risk of urogenital tract infections. Sex Transm Infect. 2022 Feb;98(1):58-61. doi: 10.1136/sextrans-2020-054816. Epub 2021 Jan 29.

    PMID: 33514681DERIVED

  • Verwijs MC, Agaba S, Umulisa MM, Uwineza M, Nivoliez A, Lievens E, van de Wijgert JHHM. Vaginal probiotic adherence and acceptability in Rwandan women with high sexual risk participating in a pilot randomised controlled trial: a mixed-methods approach. BMJ Open. 2020 May 19;10(5):e031819. doi: 10.1136/bmjopen-2019-031819.

    PMID: 32434932DERIVED

  • Verwijs MC, Agaba SK, Darby AC, van de Wijgert JHHM. Impact of oral metronidazole treatment on the vaginal microbiota and correlates of treatment failure. Am J Obstet Gynecol. 2020 Feb;222(2):157.e1-157.e13. doi: 10.1016/j.ajog.2019.08.008. Epub 2019 Aug 9.

    PMID: 31404542DERIVED

MeSH Terms

Conditions

Vaginosis, Bacterial

Condition Hierarchy (Ancestors)

Bacterial InfectionsBacterial Infections and MycosesInfectionsVaginitisVaginal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Diseases

Limitations and Caveats

The two most important limitations were the modest sample size (this trial was funded as a pilot trial) and our inability to exclude women with gonorrhea and/or chlamydia infection at the time of randomization (due to slow testing turn-around).

Results Point of Contact

Title
Prof. Janneke van de Wijgert, Chief Investigator
Organization
University of Liverpool
j.vandewijgert@liverpool.ac.uk
+447557195108

Study Officials

  • Janneke H van de Wijgert, PhD

    University of Liverpool

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Infection and Global Health

Study Record Dates

First Submitted

May 21, 2015

First Posted

June 2, 2015

Study Start

June 5, 2015

Primary Completion

February 23, 2016

Study Completion

August 6, 2018

Last Updated

July 16, 2019

Results First Posted

July 16, 2019

Record last verified: 2019-06