Clinical trial NCT06921213: Comprehensive Ambulatory Antibiotics for the Treatment of Congenital Syphilis
Official title: Comprehensive Ambulatory Antibiotics for the Treatment of Congenital Syphilis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Syphilis, Congenital
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: University College Dublin
name: University of Stellenbosch
name: Malawi Liverpool Wellcome Programme
name: University of Sydney
name: Murdoch Childrens Research Institute
name: MRC CTU at UCL
name: PHPT/AMS Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University
First posted: 2025-04-10
Enrollment: 90
Sex: ALL
Minimum age (years): 0
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Time above MIC in serum
timeFrame: From enrolment through to day 10 of the study
measure: Time above MIC in CSF
timeFrame: 10 days
measure: Adverse Events
timeFrame: Assessed from enrolment through to 24 weeks
Secondary outcomes:
measure: Clinical Outcome
timeFrame: Enrolment through to week 24
measure: AUC/MIC Ratio in serum
timeFrame: Enrolment through to day 10
measure: AUC/MIC Ratio in CSF
timeFrame: Enrolment through to day 10
Other outcomes:
Locations:
city: Jakarta
country: Indonesia
facility: Universitas Indonesia
city: Blantyre
country: Malawi
facility: Malawi Liverpool Wellcome Programme
city: Stellenbosch
country: South Africa
facility: Stellenbosch
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Michael Marks
role: PRINCIPAL_INVESTIGATOR
affiliation: University College Dublin
name: Bridget Freyne
role: PRINCIPAL_INVESTIGATOR
References: