Comprehensive Ambulatory Antibiotics for the Treatment of Congenital Syphilis (Cares-1)

London School of Hygiene and Tropical Medicine

Status and phase: Not yet enrolling; Phase 2

Conditions: Syphilis, Congenital

Treatments: Drug: Linezolid (LZD); Drug: Benzathine Penicillin G; Drug: Amoxicillin

Study type: Interventional

Funder types: Other

Identifiers

NCT06921213

31732

Details and patient eligibility

About

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.

Enrollment: 90 estimated patients

Sex: All

Ages: Under 7 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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90 participants in 3 patient groups

Oral Linezolid

Experimental group

Description:

10 day course of Linezolid twice a day

Treatment:

Drug: Linezolid (LZD)

Oral Amoxicillin

Experimental group

Description:

10 day course of Amoxicillin twice a day

Treatment:

Drug: Amoxicillin

IM Benzathine penicillin

Active Comparator group

Description:

Single IM dose of IM Benzathine penicillin

Treatment:

Drug: Benzathine Penicillin G