Evaluation of Antimicrobial Prophylaxis to Prevent Syphilis in Pregnancy in Patients at Risk in Rio de Janeiro, Brazil

Syphilis rates during pregnancy have been rising consistently in Brazil in the last decade, with a parallel increase in the rates of congenital syphilis. The state of Rio de Janeiro, in particular, has consistently had the highest rate of gestational syphilis in the country. It is critical to develop an intervention to reduce the risk of syphilis infection during pregnancy, especially for women most at risk of acquiring congenital syphilis. The investigators hypothesize that routine counseling on prevention of sexually transmitted infections (STIs) and the use of benzathine penicillin G (BPG) prophylaxis during pregnancy may help reduce the rates of syphilis in high risk pregnant populations and congenital syphilis. The investigators propose a randomized, unblinded clinical trial using BPG prophylaxis in pregnant women at higher risk of syphilis during pregnancy. The primary objective is to prevent the development of gestational syphilis and congenital syphilis through counseling on prevention of STIs, monthly treponemal and non-treponemal tests beginning in the 28th week of pregnancy and for those testing negative monthly IM injections of BPG, compared to counseling on prevention of STIs and monthly treponemal and non-treponemal tests beginning in the 28th week of pregnancy (enhanced standard of care). The primary maternal endpoint is a negative POC treponemal test and VDRL test at delivery confirming absence of maternal syphilis infection. The primary infant endpoint is absence of congenital syphilis.

The study population is pregnant persons testing negative for syphilis at 28 weeks' of pregnancy but who are at higher risk of contracting syphilis during pregnancy. The study plans to enroll at the Hospital Federal dos Servidores do Estado or at maternity hospitals. Study participants with a viable pregnancy and no significant pregnancy complications until the time of enrollment who meet the inclusion and exclusion criteria are randomized to receive counseling about prevention of STIs, enhanced serological screening, and if testing negative receive 2.4 million units of BPG IM at 28 weeks of pregnancy (+/- one week), 32 weeks (+/- one week) and 36 weeks (+/- one week) or counseling and enhanced serological screening (enhanced standard of care). The duration of the study will be 3.5 years for recruitment of participants, 6 months to complete follow-up and one additional year for data analysis, data write up and publishing of results. The duration of participation for each pregnant person will be 4 to 5 months (from 28 weeks of gestational age to delivery). Infants will be followed in the neonatal period (first 4 weeks of life).

• Number of participants who agree to the intervention and continue on the regimen after the first visit [Срок оценки: First study visit through 28 days after delivery]
• Degree of pain at the injection site from 0 to 10 according to the Numeric Ranking Scale [Срок оценки: First study visit through 28 days after delivery]
• Number of participants with any cardiovascular adverse event following injection of Benzathine Penicillin G [Срок оценки: First study visit to labor and delivery]
• Number of participants with any pregnancy complications [Срок оценки: Delivery through 4 weeks after delivery]
• Number of participants with any dermatologic adverse event following injection of Benzathine Penicillin G [Срок оценки: First study visit to labor and delivery]
• Number of participants with fever following injection of Benzathine Penicillin G [Срок оценки: First study visit to labor and delivery]
• Number of participants with any gastrointestinal adverse events following injection with Benzathine Penicillin G [Срок оценки: First study visit to labor and delivery]
• Number of participants with genitourinary adverse events following injection with Benzathine Penicillin G [Срок оценки: First study visit to labor and delivery]
• Number of participants with hepatic adverse events following injection with Benzathine Penicillin G [Срок оценки: First study visit to labor and delivery]
• Number of participants with immunologic adverse events following injection with Benzathine Penicillin G [Срок оценки: First study visit to labor and delivery]
• Number of participants with local injection site reactions following injection of Benzathine penicillin G [Срок оценки: First study visit to labor and delivery]
• Number of participants with neurologic adverse events following injection of Benzathine Penicillin G [Срок оценки: First study visit to labor and delivery]