Congenital SyphilisPhase 2PRESERvENCT07189208
Evaluation of Antimicrobial Prophylaxis to Prevent Syphilis in Pregnancy in Patients at Risk in Rio de Janeiro, Brazil
A Phase 2 study testing Benzathine penicillin 2.4 million units and Counseling and intensified testing. in people with Congenital Syphilis, run by University of California, Los Angeles at 4 sites in Brazil.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Congenital Syphilis
- What is being tested?
- Benzathine penicillin 2.4 million units and Counseling and intensified testing.
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 4 sitesBrazil
- Study dates
- 24 Sep 2025to 31 Jul 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Uncomplicated, viable pregnancy
- Elevated risk for syphilis acquisition (one or more of the following):
- Prior history of STIs last 3 years
- HIV infection
- Age < 21 years
- In a sexual partnership of < 3 mo., or > 3 sexual partners in the last 6 mo.
Show all 13Show fewer
- Late initiation of prenatal care (> 14 weeks of pregnancy)
- Residence in area where syphilis prevalence is 10% or higher.
- Ability to provide written informed consent
- No allergy to penicillin
- Prenatal care at one of the sites participating in the study
- Ongoing sexual activity during study period.
- Negative rapid treponemal test at baseline.
Who cannot join
- Non-viable pregnancy
- Very high risk pregnancy
- Inability to provide written informed consent
- Allergy to penicillin
- Positive rapid treponemal test at baseline
- Lack of sexual activity during study period.
- Any persisting coagulation disorder that would contraindicate IM injections.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil4 sites, 4 recruiting
- Not yet recruiting
Centro de Referencia e Atenção Especializada a Saúde da Mulher (CRAESM)
Duque de Caxias, Rio de Janeiro
Esaú C. João, +55 (21) 2233-0018, esaujoao@gmail.com
- Recruiting
Policlínica Hospital Municipal Duque de Caxias
Duque de Caxias, Rio de Janeiro
Esaú C. João, MD, PhD, +55 (21) 2233-0018, esaujoao@gmail.com
- Not yet recruiting
Unidade Básica de Saúde José de Freitas
Duque de Caxias, Rio de Janeiro
Esaú C. João, MD, PhD, +55 (21) 2233-0018, esaujoao@gmail.com
- Recruiting
Hospital Federal dos Servidores do Estado
Rio de Janeiro, Rio de Janeiro
About this study
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.
Read more
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
Read the detailed 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).
- Conditions
- Congenital Syphilis
- Being tested
- Benzathine penicillin 2.4 million units, Counseling and intensified testing.
- Keywords
- congenital syphilis
- Medical subject headings
- Syphilis, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Benzathine penicillin 2.4 million unitsDrug
IM injection of BPG
Counseling and intensified testing.Behavioural
Brazilian Ministry of Health guidelines for the prevention and diagnosis of maternal syphilis consist of counseling about STI prevention and syphilis testing at the first pre-natal consultation, at a subsequent consultation during or after 28 weeks of pregnancy, at delivery, and in case of abortion or stillbirth. In this study, intensified testing refers to treponemal and non-treponemal tests once every four weeks beginning as of the 28th week of pregnancy.
| Study group | Role | What they receive |
|---|---|---|
| Counseling and intensified testing and, if negative, Benzathine Penicillin G | Experimental | 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. Receives: Drug: Benzathine penicillin 2.4 million units; Behavioral: Counseling and intensified testing. |
| Counseling and intensified testing without using Benzathine Penicillin G | Active comparator | 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. Receives: Behavioral: Counseling and intensified testing. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with absence of maternal syphilis infection
Negative POC treponemal test and VDRL test following entry into the study and at the time of labor and delivery confirming absence of maternal syphilis infection. A participant developing a positive serologic result after study entry will have reached a study endpoint and will be followed off study.
Measured: Labor and delivery
Secondary outcomes (19)
Number of participants who agree to the intervention and continue on the regimen after the first visit
For acceptability, the investigators will monitor our recruitment attempts prior to study entry to evaluate how many potential participants were offered study enrollment. For participants who enroll in the study, the investigators will evaluate how many agree to the intervention and continue on the regimen after the first visit, noting any premature study discontinuation and the reason for discontinuation using a questionnaire.
Measured: 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
To assess tolerability, the investigators will offer participants an online questionnaire where they record their experience with the use of IM penicillin during the study, assessing their experience with treponemal and nontreponemal tests (both arms), the degree of pain at the injection site (0 to 10) according to the Numeric Ranking Scale in which higher scores mean worse pain, any local or systemic symptoms afterwards, duration of discomfort, or any other local or systemic findings for each study visit. The investigators will also administer a tolerability questionnaire to participants randomized to the enhanced standard of care.
Measured: First study visit through 28 days after delivery
Number of participants with any cardiovascular adverse event following injection of Benzathine Penicillin G
Cardiovascular adverse events are defined as any of following: hypotension, palpitations, syncope, tachycardia, and hypersensitivity reactions.
Measured: First study visit to labor and delivery
Number of participants with any pregnancy complications
Pregnancy complications are defined as emergency C-section or still birth.
Measured: Delivery through 4 weeks after delivery
Number of participants with any dermatologic adverse event following injection of Benzathine Penicillin G
A dermatologic adverse event will be defined as any of the following: acute, generalized rash, diaphoresis, dermatitis, infection of skin or other subcutaneous tissues, pruritus, skin discoloration, ulceration at injection site, any type of allergic reaction, or urticaria.
Measured: First study visit to labor and delivery
Number of participants with fever following injection of Benzathine Penicillin G
Fever will be defined as axillary temperature of 37.2°C or higher or rectal, oral, tympanic, or temporal artery temperature of 38°C higher.
Measured: First study visit to labor and delivery
Number of participants with any gastrointestinal adverse events following injection with Benzathine Penicillin G
A gastrointestinal adverse event will be defined as any of the following: hematochezia, nausea, diarrhea, or vomiting
Measured: First study visit to labor and delivery
Number of participants with genitourinary adverse events following injection with Benzathine Penicillin G
A genitourinary adverse event is defined as hematuria or proteinuria.
Measured: First study visit to labor and delivery
Number of participants with hepatic adverse events following injection with Benzathine Penicillin G
A hepatic adverse event is defined as increased transaminases (AST/ALT).
Measured: First study visit to labor and delivery
Number of participants with immunologic adverse events following injection with Benzathine Penicillin G
An immunologic adverse event is defined as eosinophilia or other systemic allergic reactions
Measured: First study visit to labor and delivery
Number of participants with local injection site reactions following injection of Benzathine penicillin G
Local injection site reactions are defined as discomort or aching at the injection site, pain upon touch of the injection site, erythema, swelling, induration, pruritus, or bruising.
Measured: First study visit to labor and delivery
Number of participants with neurologic adverse events following injection of Benzathine Penicillin G
Neurologic adverse events are defined as anxiety, confusion, fatigue, headache, or pain
Measured: First study visit to labor and delivery
Gestational age at delivery of live born neonates
Gestational age will be defined based on obstetric ultrasound, date of last menstrual period, or clinical exam at delivery (Capurro method).
Measured: Delivery to 28 days after delivery
Birth weight at delivery of liveborn neonates
Weight in grams
Measured: Delivery to 28 days after delivery
Number of neonates with any neonatal complications
Neonatal complications are defined as neonatal death, low birth weight (<2,500 g), preterm delivery (<37 weeks), or small for gestational age.
Measured: Delivery to 28 days after delivery
Number of neonates admitted to the intensive care unit (ICU)
Number of neonates admitted to the intensive care unit (ICU)
Measured: Delivery to 28 days after delivery
Number of pregnant participants admitted to the hospital for any reason after delivery
Number of pregnant participants admitted to the hospital for any reason after delivery
Measured: Delivery to 28 days after delivery
Number of pregnant participants admitted to the hospital due to delivery complications
Delivery complications are defined as postpartum hemorrhage, sepsis, perineal tears, or thromboembolism.
Measured: Delivery to 28 days after delivery.
Number of pregnant participants with a prolonged hospital stay following delivery
A prolonged hospital stay is defined as more than 72 hours after delivery
Measured: Delivery to 28 days after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2025
- Study start24 Sep 2025
- Primary completion1 Dec 2029 (estimated)
- Study completion31 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital SyphilisStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Karin Nielsen, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07189208
- Sponsor's protocol ID
- 24-001337
- Other IDs
- R01AI187414
- Acronym
- PRESERvE
- Status last verified
- May 2026
- First submitted
- 8 Sep 2025
- Last updated
- 1 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No