A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

Schwebke, Jane R.; Marrazzo, Jeanne M.; Beelen, Andrew P.; Sobel, Jack D.

doi:10.1097/olq.0000000000000300

Cited by 26 publications

(15 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A new therapy for the treatment of BV that avoids issues of conventional antibiotics, such as systemic exposure, candidiasis and antibiotic resistance, and has a novel mechanism of action targeting biofilms, offers a promising potential treatment modality for BV. In this study, the clinical cure rate for 1% astodrimer at day 9-12 (74.1%) compares favorably to cure rates reported for conventional antibiotic products such as oral secnidazole (57.9%) [21] and metronidazole 1.3% gel (46%) [22] using comparable cure criteria assessed at a similar timeframe. The cure rate also compares favorably with BV cure rates obtained with an experimental boric acid/ethylenediamine tetra acetic acid (EDTA) vaginal gel intended to target biofilm in BV (50%) [23].…”

Section: Discussionsupporting

confidence: 60%

A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Astodrimer Gel contains a novel dendrimer intended to treat and prevent bacterial vaginosis. We assessed the efficacy and safety of Astodrimer Gel for treatment of bacterial vaginosis. Methods 132 women with bacterial vaginosis were randomized 1:1:1:1 to Astodrimer 0.5% (N = 34), 1% (N = 33), or 3% (N = 32) Gel or hydroxyethyl cellulose placebo gel (N = 33) at a dose of 5 g vaginally once daily for 7 days at 6 centers in the United States. The primary endpoint was clinical cure (no bacterial vaginosis vaginal discharge and no more than one of 1) vaginal pH �4.5; 2) �20% clue cells; or 3) positive whiff test) at study days 21-30. Secondary analyses included clinical cure at study days 9-12, patient-reported symptoms, acceptability and adverse events. Results The Astodrimer 1% Gel dose was superior to placebo for the primary and selected secondary efficacy measures in the modified intent-to-treat population. Clinical cure rates at day 9-12 were superior to placebo for the Astodrimer 3%, 1% and 0.5% Gel groups (62.5% [15/ 24; P = .002], 74.1% [20/27; P < .001], and 55.2% [16/29; P = .001], respectively, vs. 22.2% [6/27]). At day 21-30, clinical cure rates were 46.2% (12/26) for the 1% dose vs. 11.5% for placebo (3/26; P = .006). A greater proportion of patients reported absence of vaginal discharge and vaginal odor at day 9-12 and day 21-30 for Astodrimer Gel groups compared with placebo. Adverse events considered potentially treatment-related occurred in only 25% of Astodrimer Gel-treated patients vs. 22% of placebo patients.

show abstract

Section: Discussionsupporting

confidence: 60%

A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is a first generation nitroimidazole, which was initially indicated for the management of trichomoniasis (Moffett and Mcgill, 1960 ) but was then shown to be effective against anaerobic microorganisms (Tally et al, 1975 ). However, metronidazole therapy is associated with several side effects such as nausea, vomiting and gastrointestinal complaints (Schwebke and Desmond, 2011 ; Abdali et al, 2015 ; Chavoustie et al, 2015 ; Schwebke et al, 2015 ). Clindamycin is also an antimicrobial agent for BV treatment (Centers for Disease Control and Prevention, 2015 ), with similar efficacy as metronidazole (Paavonen et al, 2000 ; Beigi et al, 2004 ).…”

Section: Current Bv Antibiotic Therapeutic Optionsmentioning

confidence: 99%

Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions

et al. 2016

View full text Add to dashboard Cite

Bacterial vaginosis (BV) is the most common genital tract infection in women during their reproductive years and it has been associated with serious health complications, such as preterm delivery and acquisition or transmission of several sexually transmitted agents. BV is characterized by a reduction of beneficial lactobacilli and a significant increase in number of anaerobic bacteria, including Gardnerella vaginalis, Atopobium vaginae, Mobiluncus spp., Bacteroides spp. and Prevotella spp.. Being polymicrobial in nature, BV etiology remains unclear. However, it is certain that BV involves the presence of a thick vaginal multi-species biofilm, where G. vaginalis is the predominant species. Similar to what happens in many other biofilm-related infections, standard antibiotics, like metronidazole, are unable to fully eradicate the vaginal biofilm, which can explain the high recurrence rates of BV. Furthermore, antibiotic therapy can also cause a negative impact on the healthy vaginal microflora. These issues sparked the interest in developing alternative therapeutic strategies. This review provides a quick synopsis of the currently approved and available antibiotics for BV treatment while presenting an overview of novel strategies that are being explored for the treatment of this disorder, with special focus on natural compounds that are able to overcome biofilm-associated antibiotic resistance.

show abstract

“…Other FDA approved treatments for BV include tinidazole taken orally for multiple days [12], a single dose metronidazole gel [13] and a single dose clindamycin cream treatment [14]. Even with a variety of antimicrobial agents available for the treatment of BV, recurrence occurs after 12 months for almost 60% of women [15].…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin

et al. 2017

View full text Add to dashboard Cite

Secnidazole, a 5-nitroimidazole with a longer half-life, is structurally related to metronidazole and tinidazole. For treatment of bacterial vaginosis (BV), secnidazole is a suitable single-dose oral drug having a longer serum half-life than metronidazole. The objective of this study was to evaluate the antimicrobial susceptibility of vaginal isolates of facultative and anaerobic bacteria to secnidazole, metronidazole, tinidazole and clindamycin. A total of 605 unique BV-related bacteria and 108 isolates of lactobacilli recovered from the human vagina of US women during the years 2009–2015 were tested for antimicrobial susceptibility by the agar dilution CLSI reference method to determine the minimal inhibitory concentration (MIC). The MIC90 (μg/mL) for secnidazole was similar to metronidazole and tinidazole for Anaerococcus tetradius (secnidazole: MIC90 2; metronidazole: MIC90 2; tinidazole: MIC90 4), Atopobium vaginae (32; >128; 128), Bacteroides species (2; 2; 2), Finegoldia magna (2; 2; 4), Gardnerella vaginalis (128; 64; 32), Mageeibacillus indolicus (2; 2; 2), Megasphaera-like bacteria (0.5; 0.25; 0.5), Mobiluncus curtisii (128; >128; >128) and Mobiluncus mulieris (>128; >128; >128), Peptoniphilus lacrimalis (4; 4; 4) and Peptoniphilus harei (2; 2; 4), Porphyromonas species (0.25; 0.5; 0.25), Prevotella bivia (8; 8; 8), Prevotella amnii (2; 1; 2) and Prevotella timonensis (2; 2; 2). In this evaluation, 14 (40%) of 35 P. bivia, 5 (14%) of 35 P. amnii and 21 (58%) of 36 P. timonensis isolates were resistant to clindamycin with MIC values of >128 μg/mL. Secnidazole, like metronidazole, was superior to clindamycin for Prevotella spp., Bacteroides spp., Peptoniphilus spp., Anaerococcus tetradius and Finegoldia magna. Clindamycin had greater activity against Atopobium vaginae, Gardnerella vaginalis and Mobiluncus spp. compared to the nitroimidazoles. All 27 Lactobacillus crispatus, 26 (96%) of 27 L. jensenii, 5 (19%) of 27 L. gasseri and 18 (67%) of 27 L. iners isolates were susceptible to clindamycin (MIC ≤2) while the MIC90 for all lactobacilli tested was >128 ug/mL for secnidazole, metronidazole and tinidazole. Secnidazole has similar in vitro activity against the range of microorganisms associated with BV compared to metronidazole or tinidazole. Further, secnidazole spares lactobacilli, a characteristic which is desirable in drugs used to treat bacterial vaginosis.

show abstract

A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

Abstract: A phase 3 randomized study of single-dose metronidazole vaginal gel 1.3% versus vehicle gel in participants with bacterial vaginosis demonstrated superior cure rates in the metronidazole treatment group.

Cited by 26 publications

References 15 publications

A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions

Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin

Contact Info

Product

Resources

About