Efficacy and Safety of Single Oral Dosing of Secnidazole for Trichomoniasis in Women: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Delayed-Treatment Study.

BACKGROUND: Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection. We evaluated the efficacy and safety of secnidazole vs placebo in women with trichomoniasis. METHODS: Women with trichomoniasis, confirmed by a positive T. vaginalis culture, were randomized to single-dose oral secnidazole 2 g or placebo. The primary endpoint was microbiological test of cure (TOC) by culture 6-12 days after dosing. At the TOC visit, participants were given the opposite treatment. They were followed for resolution of infection afterward and offered treatment at subsequent visits, if needed. Fifty patients per group (N = 100) provided approximately 95% power to detect a statistically significant difference between treatment groups. RESULTS: Between April 2019 and March 2020, 147 women enrolled at 10 sites in the United States. The modified intention-to-treat (mITT) population included 131 randomized patients (secnidazole, n = 64; placebo, n = 67). Cure rates were significantly higher in the secnidazole vs placebo group for the mITT population (92.2% [95% confidence interval {CI}: 82.7%-97.4%] vs 1.5% [95% CI: .0%-8.0%]) and for the per-protocol population (94.9% [95% CI: 85.9%-98.9%] vs 1.7% [95% CI: .0%-8.9%]). Cure rates were 100% (4/4) in women with human immunodeficiency virus (HIV) and 95.2% (20/21) in women with bacterial vaginosis (BV). Secnidazole was generally well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were vulvovaginal candidiasis and nausea (each 2.7%). No serious TEAEs were observed. CONCLUSIONS: A single oral 2 g dose of secnidazole was associated with significantly higher microbiological cure rates vs placebo, supporting a role for secnidazole in treating women with trichomoniasis, including those with HIV and/or BV. CLINICAL TRIALS REGISTRATION: NCT03935217.

Preventing ectopic pregnancies: how often does transperitoneal transmigration of sperm occur in effecting human pregnancy?

OBJECTIVE: Transperitoneal transmigration of sperm constitutes the mechanism by which ectopic pregnancies occur in unilaterally obstructed fallopian tubes. This study was undertaken to determine how often sperm transmigrate across the peritoneal cavity to effect human pregnancy. DESIGN: In women with non-communicating rudimentary uterine horn pregnancies, the ratio of total uterine horn pregnancies to prior contralateral hemi-uterine pregnancies was calculated to infer the overall transperitoneal sperm transmigration rate. The prior parity frequency distribution was also determined to calculate the best-fit per-pregnancy probability of attaining a rudimentary horn pregnancy with each subsequent gestation using maximum likelihood estimation. SETTING: 20th century. SAMPLE: Non-communicating rudimentary uterine horn pregnancies reported from 40 countries. METHODS: Two hundred and seventy-two cases were identified using manual and computerised searches of Index Medicus, Excerpta Medica, the Index-Catalogue of the Library of the Surgeon-General's Office and standard reference tracing. MAIN OUTCOME MEASURES: The ratio of total prior non-rudimentary uterine horn pregnancies to rudimentary uterine horn pregnancies and the frequency distribution of prior maternal parities. RESULTS: Prior to the incident 272 uterine horn pregnancies, the number of observed pregnancies was 292 (ratio = 0.93), implying an aggregate sperm transmigration rate of 0.48. Using the prior parity frequency distribution, the best-fit probability of attaining a rudimentary horn gestation per-pregnancy was 0.51 (95% CI 0.48-0.56). CONCLUSIONS: Intraperitoneal sperm transmigration occurs approximately half the time in effecting spontaneous human pregnancies. To minimise the risk of ectopic tubal pregnancy in woman with unilaterally damaged fallopian tubes, salpingectomy should be the preferred surgical treatment, rather than attempting tubal salvage and repair.