Syphilis, Congenital
Conditions
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.
Interventions
DRUGLinezolid (LZD)
Ten day course. Oral Linezolid dosed at 10mg/kg twice a day.
DRUGAmoxicillin
Ten day course. Oral Linezolid dosed at 50mg/kg twice a day.
Single IM dose 50,000iu/kg
Sponsors
University College Dublin
University of Stellenbosch
Malawi Liverpool Wellcome Programme
University of Sydney
Murdoch Childrens Research Institute
MRC CTU at UCL
PHPT/AMS Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
It is not possible to blind the intervention to either participants or care providers given variation in route of administration and duration of therapy. Individuals assessing clinical and laboratory outcomes will be blinded to study group.
Eligibility
Sex/Gender
ALL
Age
0 Days to 7 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
Indonesia, Malawi, South Africa
Contacts
Primary ContactSarah Prentice
Outcome results
None listed