Outpatient antibiotic options for newborns with congenital syphilis

Comprehensive Ambulatory Antibiotics for the Treatment of Congenital Syphilis

This trial tests whether giving certain antibiotics as outpatient treatment is safe and achieves good drug levels for newborns born at risk of congenital syphilis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 0 Days to 7 Days
• Sex: All
• Sponsor: London School of Hygiene and Tropical Medicine (Academic / other)
• Locations: 3 sites (Jakarta and 2 other locations)
• Trial ID: NCT06921213 on ClinicalTrials.gov

What this trial studies

CARES-1 is a randomized, open-label phase II pharmacokinetic and safety study of ambulatory antibiotic regimens for neonates born at risk of asymptomatic congenital syphilis. Eligible newborns are randomized to receive outpatient courses that include linezolid, amoxicillin, or benzathine penicillin G, with serial drug-level measurements and safety monitoring. The study records pharmacokinetics, adverse events, and short-term clinical outcomes to determine if outpatient dosing reaches therapeutic concentrations and is well tolerated. The trial is led by the London School of Hygiene and Tropical Medicine with collaborating sites in Indonesia, Malawi, and South Africa.

Who should consider this trial

Good fit: Newborns born to mothers who tested positive for syphilis in pregnancy and who are untreated, incompletely treated, or otherwise considered at risk, but who are asymptomatic at birth, are the intended participants.

Not a fit: Infants who are symptomatic with confirmed congenital syphilis, clinically unstable, or have known allergies to the study antibiotics are unlikely to benefit from the outpatient regimens tested.

Why it matters

Potential benefit: If successful, this could provide safe outpatient antibiotic options that reduce hospital stays and improve access to timely treatment for newborns at risk of congenital syphilis.

How similar studies have performed: Benzathine penicillin G is the established standard of care for congenital syphilis, but ambulatory regimens using drugs like linezolid or amoxicillin in newborns are largely untested and prior data are limited.

Eligibility criteria

Inclusion Criteria:

1. Infants at risk of congenital syphilis at birth defined as:

   1. an infant born to a mother who tests positive for syphilis in pregnancy using registered and licensed locally-available diagnostic tests for example but not limited to a Treponemal rapid POCT, an RPR or both.

      AND
   2. the mother is untreated in the current pregnancy defined as:

   i. she tested positive at antenatal care and received no treatment OR ii. she was never tested during antenatal care OR iii. she tested negative at antenatal care and positive on re-testing at delivery

   OR c. the mother is inadequately treated in the current pregnancy defined as:

   i. Having received a non-penicillin based treatment regimen; and/or ii. Does not have documentation of 3 doses of IM Benzathine Penicillin, given 7-10 days apart, with the last dose given \> 30 days prior to delivery OR b. The mother was adequately treated in the current pregnancy BUT considers herself at risk of re-infection following a midwife delivered explanation of risk (partner treatment, multiple partners etc).
2. Infants who are asymptomatic for a diagnosis of congenital syphilis following application of a clinical proforma by the study team (Appendix 1)
3. Infants who are less than \<= 7 days of life AND with a post-menstrual age (PMA) of 34-42 weeks (Appendix 2).
4. Infants who are tolerating enteral feeds, including if they are being administered by an NG tube.

Exclusion Criteria:

\- 1. The infant's clinical condition at birth or prior to randomisation requires ongoing (\> 48 hours) treatment with antibiotics with the potential for anti-treponemal activity i.e. B-lactams, Cephalosporins, Carbapenems.

2\. They have a birthweight \<2kg 3. They are nil by mouth. 4. They have a life-limiting congenital anomaly

Where this trial is running

Jakarta and 2 other locations

• Universitas Indonesia — Jakarta, Indonesia (Not_yet_recruiting)
• Malawi Liverpool Wellcome Programme — Blantyre, Malawi (Not_yet_recruiting)
• Stellenbosch — Stellenbosch, South Africa (Recruiting)

Study contacts

• Principal investigator: Michael Marks — London School of Hygiene and Tropical Medicine
• Study coordinator: Sarah Prentice

Conditions Syphilis, Congenital