Comprehensive Ambulatory Antibiotics for the Treatment of Congenital Syphilis

Phase 2

Not yet recruiting

• Conditions: Syphilis, Congenital
• Interventions: Drug: Linezolid (LZD); Drug: Amoxicillin; Drug: Benzathine Penicillin G

• Registration Number: NCT06921213
• Lead Sponsor: London School of Hygiene and Tropical Medicine

Brief Summary

CARES-1 is a randomised, open-label, phase II pharmacokinetic (PK) and safety study of ambulatory antibiotics for the treatment of neonates with "all-risk" asymptomatic congenital syphilis.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-25
• Study First Submitted QC: 2025-04-03
• Study First Posted: 2025-04-10
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-04
• Study Start: 2025-10-01
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral Linezolid	Linezolid (LZD)	10 day course of Linezolid twice a day
Oral Amoxicillin	Amoxicillin	10 day course of Amoxicillin twice a day
IM Benzathine penicillin	Benzathine Penicillin G	Single IM dose of IM Benzathine penicillin

Primary Outcome Measures

Name	Time	Method
Time above MIC in CSF	10 days	Time above MIC in CSF throughout the dosing interval
Adverse Events	Assessed from enrolment through to 24 weeks	The proportion of individuals experiencing an adverse event through to week 24. The trial will record SAE, SUSARS, and drug related AEs of grade 3 or higher.
Time above MIC in serum	From enrolment through to day 10 of the study	Time above MIC of T. pallidum for the dosing interval in serum

Secondary Outcome Measures

Name	Time	Method
AUC/MIC Ratio in serum	Enrolment through to day 10	Proportion of individuals achieving an AUC/MIC ratio ≥100 in serum
AUC/MIC Ratio in CSF	Enrolment through to day 10	Proportion of individuals achieving an AUC/MIC ratio ≥100 in CSF
Clinical Outcome	Enrolment through to week 24	Proportion of infants who have clinical or laboratory evidence of congenital syphilis as adjudicated by an expert committee, blinded to treatment allocation, based on clinical and laboratory data.

Trial Locations

Locations (3)

Stellenbosch; 🇿🇦 Stellenbosch, South Africa

Universitas Indonesia; 🇮🇩 Jakarta, Indonesia

Malawi Liverpool Wellcome Programme; 🇲🇼 Blantyre, Malawi