An experimental vaginal gel significantly reduced urogenital chlamydia and gonorrhea in women at high risk of infection, compared to placebo, opening up new possibilities for an on-demand prevention option. Investigators in a randomized trial reported these results in the American Journal of Obstetrics and Gynecology.
The rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are on the rise in the United States, despite wide availability of male and female condoms to prevent sexually transmitted infections. This suggests that women need a more discreet method that they can better control. Other vaginal microbicides developed in recent decades have not shown good results for protection against STIs or HIV in clinical trials.
The slightly alkaline nature of human semen has the potential to neutralize vaginal pH after sex, creating an environment more vulnerable to STIs. EVO100 is an experimental antimicrobial bioadhesive vaginal gel that contains L-lactic acid, citric acid and potassium bitartrate. In preclinical studies, it was found to be very effective in buffering the alkaline properties of human semen and maintaining vaginal pH levels. Patients generally tolerated it well, apart from some reports of vaginal itching and burning.
In the AMPREVENCE study, a phase 2b / 3, double-blind, placebo-controlled, randomized trial, Todd Chappell, MD, of Adams Patterson Gynecology & Obstetrics, Memphis, and colleagues tested the efficacy and safety of EVO100 to prevent chlamydia and gonorrhea. .
Researchers randomized 1: 1,860 healthy, sexually active women to receive either EVO100 (n = 426) or placebo (n = 434). Participants had been diagnosed or treated for these STIs up to 16 weeks prior to enrollment. Of the participants, 335 women in the EVO100 arm and 335 women in the placebo arm completed the study.
In this cohort, 764 women (EVO100: n = 376; placebo: n = 388) declared to have used one or the other of the products. These women represented the "safety analysis population", a predefined population for statistical analysis.
Participants were on average almost 28 years old and had a median body mass index of 28.9 kg / m 2, and represented several racial / ethnic groups: White (54.3% [467/860]), African American (41.6% [358/860]) and non-Hispanic / Latin American ethnicity (67.1% [577/860]).
Women were instructed to apply the drug within an hour of starting sexual intercourse. Investigators scheduled follow-up visits every 4 weeks during the 16-week study period, to obtain repeat CT / GC evaluations, review diary entries, and collect information on adverse reactions and use. concomitant medications. Upon registration, participants agreed to return to the clinic on each study visit. If a woman missed a visit, the study site would follow up by phone after the missed assessment visit.
Participants reported a mean number of 16 coital events (EVO100, 15.7 [13.5]; placebo, 16.3 [15.8]). The EVO100 significantly reduced the incidence of STIs for both types of STIs. CT infection rates among EVO100 users were 4.8% (14/289), half of what they were among placebo users (9.7% [28/290]) ( P = 0.0256). The experimental method was even more effective in women eligible for GC analysis: infection rates were on average 0.7% (2/280), compared to 3.2% (9/277) in the group placebo, a relative reduction in risk of 78% ( P = .0316).
By examining the entries in the electronic participant diary, investigators reported similar compliance rates in both treatment arms. However, additional sensitivity analyzes in populations eligible for CT and CG on adherence yielded significantly different results.
Users of EVO100 in the CT population who used the product as directed 100% of the time were significantly less likely to be infected, compared to the placebo group (2.3% vs. 16.9%, P = .0012). However, investigators found no significant difference in infection rates among women with lower compliance rates in the two groups. In comparison, they found no major difference in GC infection rates between the control and EVO100 groups, regardless of compliance rates, possibly due to the small number of GC infections reported. The observed adverse events correlated with the known safety profile of the drug.
Most participants said they would likely recommend EVO100 to other women and continue to use this preventative treatment.
A small GC subgroup caused by fewer cases of infection and reliance on participants' self-report of coital incidents may have limited study results. "While the use of electronic journals is useful for collecting study data, it can encourage adherence and efficacy which may be higher in the 'real' population outside of a clinical trial setting. Noted Chappell and his colleagues.
According to investigators, this is the first prospective randomized trial to study the use of an antimicrobial bioadhesive vaginal gel to prevent CT and GC infections. "EVO100 has the potential to address an unmet need for women's sexual health as a new, on-demand, female-controlled option that reduces the risk of urogenital CT and GC infections," concluded the authors.
The Food and Drug Administration has already approved EVO100 as a contraceptive option (Phexxi), Chappell said in an interview. The next steps are to conduct a phase 3 trial, which is currently underway. "If the results are positive, we will submit to the FDA for review and approval of EVO100" to prevent these STIs.
These are promising results, said Catherine Cansino, MD, MPH, associate clinical professor in the Department of Obstetrics and Gynecology at the University of California at Davis in an interview. It's always worth looking for effective treatments, "especially those that aren't traditional antibiotics to reduce the risk of antibiotic resistance," said Cansino, who was not part of the study. This is why the EVO100 is such an attractive option.
Future studies should focus on a larger population, she continued. "The population studied by this study is not the general population - these women had already had an infection at some time," which means that they are potentially at higher risk of re-infection. "Looking at their likelihood of being infected again, it's hard to know if it would be the same or different from the general population." While the drug appears to cause a decrease in new infections, the relative risk reduction is actually greater than reported. If the reinfection rate for this population is lower because people who have had infections have safer sex, the relative risk reduction would be lower, Cansino explained.
Chappell and several co-authors received research funding from Evofem Biosciences.
This article originally appeared on MDedge.com, which is part of the Medscape Professional Network.
https://www.medscape.com/viewarticle/949053?src=rss
