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

University of California, Los Angeles (UCLA)

Status and phase: Enrolling; Phase 2

Conditions: Congenital Syphilis

Treatments: Drug: Benzathine penicillin 2.4 million units; Behavioral: Counseling and intensified testing.

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07189208

24-001337

R01AI187414 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The goal of this clinical trial is to learn if benzathine penicillin works to prevent maternal syphilis. It will also learn about the safety of benzathine penicillin. The main questions it aims to answer are:

• Does benzathine penicillin lower the rate of syphilis in pregnancy?
• What medical problems do participants have when taking benzathine penicillin? Researchers will compare benzathine penicillin to routine care to see if benzathine penicillin works to prevent syphilis.

Participants will:

• Take benzathine penicillin or receive routine care during the third trimester of pregnancy
• Visit the clinic once a month for injections and tests
• Report any reactions to benzathine penicillin to the study team

Full description

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).

Enrollment: 500 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Uncomplicated, viable pregnancy

2. Elevated risk for syphilis acquisition (one or more of the following):

   1. Prior history of STIs last 3 years
   2. HIV infection
   3. Age < 21 years
   4. In a sexual partnership of < 3 mo., or > 3 sexual partners in the last 6 mo.
   5. Late initiation of prenatal care (> 14 weeks of pregnancy)
   6. Residence in area where syphilis prevalence is 10% or higher.

3. Ability to provide written informed consent

4. No allergy to penicillin

5. Prenatal care at one of the sites participating in the study

6. Ongoing sexual activity during study period.

7. Negative rapid treponemal test at baseline.

Exclusion criteria

1. Non-viable pregnancy
2. Very high risk pregnancy
3. Inability to provide written informed consent
4. Allergy to penicillin
5. Positive rapid treponemal test at baseline
6. Lack of sexual activity during study period.
7. Any persisting coagulation disorder that would contraindicate IM injections.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 2 patient groups

Counseling and intensified testing and, if negative, Benzathine Penicillin G

Experimental group

Description:

Counseling about prevention of STIs at each pre-natal visit. Treponemal and non-treponemal tests every four weeks beginning at the 28th week of pregnancy and at delivery. If negative, IM injection of 2.4 million units of Benzathine Penicillin G. If positive, syphilis treatment based on the guidelines of the Brazilian Ministry of Health.

Treatment:

Behavioral: Counseling and intensified testing.

Drug: Benzathine penicillin 2.4 million units

Counseling and intensified testing without using Benzathine Penicillin G

Active Comparator group

Description:

Counseling about prevention of STIs at each pre-natal visit. Treponemal and non-treponemal tests every four weeks beginning at the 28th week of pregnancy and at delivery. If positive, syphilis treatment based on the guidelines of the Brazilian Ministry of Health.

Treatment:

Behavioral: Counseling and intensified testing.