4.1. Summary of findings
With regard to astodrimer gel versus placebo for treatment of bacterial
vaginosis, we included three studies comprising four independent RCTs
with a total of 1165 patients (614 and 551 patients received astodrimer
gel and placebo, respectively). Results obtained from this systematic
review and meta-analysis are clinically significant and all the included
RCTs are of high quality and low risk of bias.
Astodrimer gel was significantly superior to placebo for all pooled
efficacy outcomes, including clinical cure rate, Nugent cure rate,
patient self-reported absence of vaginal odor/discharge, resolution of
Amsel criteria and percentage of patients who received rescue therapy.
These efficacy outcomes consistently favored, without heterogeneity,
astodrimer gel over placebo at subgroup analyses at 9-12 and 21-30 days.
In 2008, a workshop was conducted by bacterial vaginosis experts from
United States National Institutes of Health (NIH), National Institute of
Allergy and Infectious Diseases (NIAID) and Department of Health and
Human Services (DHHS).30 The workshop recommended
timeframes of 7-10 and 35-40 days (posttreatment commencement) for
assessment of ‘early’ and ‘late’ treatment efficacy, respectively. For
the included studies in this review, the timeframes 9-12 and 21-30 days
are relatively close to the ones recommended by the
workshop.30 Nonetheless, long-term follow-up periods
are needed to concretely conclude the efficacy of astodrimer gel in
sustaining therapeutic cure and preventing relapse.
The pooled clinical cure rate for bacterial vaginosis at 9-12 days of
59% is relatively analogous to an experimental anti-infective drug
TOL-463 (50%)31 and standard of care antibiotics,
such as metronidazole 1.3% gel (46%)32 and 2-gram
secnidazole (58%).33 Interestingly, the pooled
clinical cure rate at 21-30 days was reduced by almost half (30%),
suggesting that recurrence of bacterial vaginosis took place. However,
this proportion is largely equivalent to metronidazole 0.75% gel
administered for five days (29%) in patients with bacterial
vaginosis.34
Clinically, bacterial vaginosis is characterized by distressing thin
white vaginal discharge and fish-like odor.35 Both
symptoms negatively impact infected women at multiple levels, including
physically, sexually, emotionally and socially.36Thus, the qualitative and speed of resolution of these symptoms are
critically important. Chavoustie et al.22 and Waldbaum
et al.23 demonstrated that more than half the of
patients who received astodrimer 1% gel had resolution of vaginal odor
within as early as one day post-initiation of treatment. This finding
contrasts satisfactorily when compared to the relatively longer median
time to resolution of vaginal odor of two and three days for
metronidazole 1.3% and 0.75% gel, respectively.34
Waldbaum et al.23 used three different concentrations
of astodrimer gel (0.5%, 1%, and 3%). Interestingly, the mid-dose 1%
was associated with the best outcomes, in terms of efficacy and safety.
This observation is in agreement with the postulation that treatment of
bacterial vaginosis with astodrimer gel rectifies the dysbiotic vaginal
environment and reestablishes equilibrium of the normal vaginal
microbiota.23 Thus, higher doses of astodrimer gel may
negatively exhibit a suppressing impact on normal vaginal bacterial
flora, namely lactobacilli. On the other hand, lower doses of astodrimer
gel may be not adequate enough to exert an antimicrobial effect. This
phenomenon is noted with rifaximin whereby a mid-range dose is
associated with the maximum cure proportion in patients with bacterial
vaginosis.37 Based on the efficacy and safety of
astodrimer 1% gel, one phase III38 and two phase II
clinical trials were carried out.22 Due to the small
number of included studies, we could not perform meta-regression for the
different doses.
With respect to safety profile, astodrimer gel demonstrated equal
tolerability to placebo for all pooled safety outcomes, expect for
vulvovaginal candidiasis and treatment-related vulvovaginal candidiasis.
The pooled proportion of drug-related vulvovaginal candidiasis was only
4.9% (n=31/639) and this proportion compares favorably when contrasted
to oral 2-gram secnidazole (13.6%).33 This overall
safety of astodrimer gel can be ascribed to its favorable
pharmacokinetics, in terms of topical application and decreased systemic
absorption20, 21 when compared to conventional
antibiotics.