This is a single center, prospective trial, which comprises of a pre-post study design
that will be looking at the vaginal microbiome makeup of participants before and after a
four-week course of Phexxi. The primary outcomes will be an increase in lactic
acid-forming lactobacilli, as well as a decrease in patient-reported symptoms of
vulvovaginitis.
This study will be based at the Queen's Medical Center (QMC), POB1 Suite 1004. Eligible
patients will be approached by participating clinicians (all doctors providing care at
the 1004 clinic) to assess interest in study participation.. The principal investigator
will review the weekly schedule for the 1004 clinic and alert the attending physicians of
patients who may be eligible for the study based on chart review. A HIPAA waiver will be
required for this stage of recruitment, as the principal investigator would otherwise not
be accessing these patient's charts. The attending physician staffing the 1004 clinic
will ask the flagged patients if they are interested in learning about the study and
review general study objectives with patients. If the patient is interested in
participating, the research associates will approach the patient to more thoroughly
screen, then conduct the informed consent process. Informed consent will be collected
from every participant prior to the start of the study.
After obtaining informed consent, the research team will review standardized instructions
for using the study medication with the patient and the research associate will provide a
take-home kit including all of the study materials, including instructions for collecting
each swab and for returning the samples. Samples will be self-collected by participants
at their home at intervals specified in the study instructions. All materials provided to
the patient will be pre-labeled with their study ID, protecting each participant's PHI.
No collections will take place in-clinic. These materials include all surveys, patient's
diary, and all swab vials. The three collection points are as follows: 1) baseline, prior
to starting intervention (see below for recommendations on collecting baseline swab), 2)
after completion of the intervention (30 days after baseline collection), and 3) 30 days
after completion of the intervention (60 days after baseline collection).
All vaginal swabs must be frozen within 48 hours of collection. As such, the participants
will be asked to send their samples within 24 hours in order to give adequate time for
delivery to the storage facility and be asked to collect their specimens between Sunday
and Thursday so samples can reach the facility during business hours. Freezing will occur
at the research site. Each patient's study kit will include a prepaid shipping envelope,
which the participant can use to mail or drive their specimen to the research team who
will then place it in the freezer until it is ready for analysis.
The first phase of the study will include an assessment and classification of patients'
vaginal microbiome prior to receipt of the intervention. To get the best representation
of the participant's baseline microbiome, the participant will be asked to collect their
baseline swab no sooner than 10 days after menses, as menses-induced changes in the
microbiome have been shown to resolve after this time12. For similar reasons, if
participants are being treated with an acute course of antibiotics or antifungals at the
time of recruitment, they will be asked to wait 10 days after the completion of their
medication course before collecting their baseline swab. There will be two additional
time points for collection: collection 2) at the end of the 30 day intervention, and
collection 3) 30 days after completion of the intervention.
Once received at the research site, samples will be stored in a specimen freezer at -80
degrees F until all specimens are received, at which point they will analyzed using
NextGen sequencing, a DNA sequencing technology that will identify the genetic makeup of
their specimens. This will be done to sequence the genome of the bacteria of the
microbiome, not the patient's genetic material. The first phase of the study will also
include a survey, which will collect demographic information from each participant, as
well as assess patients' current acceptability of a vaginal gel for prophylactic use,
their most bothersome symptoms, and how their quality of life is affected by recurrent
vulvovaginitis. The specific information collected from each participant can be found
below in Data Analysis. The survey used to measure this will be the Vulvovaginal Symptom
Questionnaire (VSQ), which has been validated for the purposes stated above. There will
also be an added space in the survey provided for open-ended answers and comments.
Measurement for primary outcomes will be done using two separate methods. In order to
assess for the presence of lactic acid-forming organisms before and after the lactic acid
gel intervention, NextGen DNA sequencing will be completed on self-collected samples
submitted by participants. The analysis of these samples will be performed by Dr. Miller,
at an in-house lab run by the UH Maternal Fetal Medicine division. In order to assess for
patient-experienced symptoms, survey B will be administered prior to, immediately after,
and 30 days after intervention.
In order to measure our secondary outcome, Survey C will be administered at collection
points 2 and 3 of the vaginal swabs. This survey is a validated tool to assess for the
acceptability, appropriateness, and feasability of an intervention (Acceptability of
Intervention Measure, or AIM, Intervention Appropriateness measure, or IAM, and
Feasibility of Intervention Measure, or FIM).
The intervention will take place on a rolling basis, as patient participation will have
no bearing on other participants. The intervention itself will take place over thirty
days. 8 pre-filled vaginal inserters with vaginal gel, will be provided to each of the
participants with verbal and written instructions for application. Patients will be
instructed to use Phexxi twice per week, on the same days every week. Throughout the 30
days, participants will also be asked to keep a diary of events occurring when they used
the product, such as intercourse or menses, as well as record any symptoms or side
effects they noticed when using the product. The diary can be sent back with the second
specimen vial. Disposal of the product may be done in a regular waste basket.
Approximately 30 days after completion of the intervention, participants will receive an
email reminder to collect and send a third collection swab in for analysis. This email
will also include the link for the third and final set of surveys.
