Syphilis, CongenitalPhase 2Cares-1NCT06921213
Comprehensive Ambulatory Antibiotics for the Treatment of Congenital Syphilis
A Phase 2 study testing Linezolid (LZD), Amoxicillin and Benzathine Penicillin G in people with Syphilis, Congenital, run by London School of Hygiene and Tropical Medicine at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 7 days
- Conditions the study is for
- Syphilis, Congenital
- What is being tested?
- Linezolid (LZD), Amoxicillin and Benzathine Penicillin G
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 4 May 2026to 30 Jun 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants at risk of congenital syphilis at birth defined as:
- 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
- the mother is untreated in the current pregnancy defined as:
- 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:
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- 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).
- Infants who are asymptomatic for a diagnosis of congenital syphilis following application of a clinical proforma by the study team (Appendix 1)
- Infants who are less than <= 7 days of life AND with a post-menstrual age (PMA) of 34-42 weeks (Appendix 2).
- Infants who are tolerating enteral feeds, including if they are being administered by an NG tube.
Who cannot join
- 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 locations and contacts
3 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 3 countries
Indonesia1 site, 1 recruiting
- Recruiting
Universitas Indonesia
Jakarta
Phoebe Williams, +61 2 9351 2222, phoebe.williams@sydney.edu.au <phoebe.williams@sydney.edu.au>
Malawi1 site, 1 recruiting
- Recruiting
Malawi Liverpool Wellcome Programme
Blantyre
Mary Mc Cauley, +265 111 81 19 18, mmccauley@mlw.mw
South Africa1 site, 1 recruiting
- Recruiting
Stellenbosch
Stellenbosch
Lisa Frigati, +27 21 808 9111, frigati@sun.ac.za
About this study
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.
- Conditions
- Syphilis, Congenital
- Being tested
- Linezolid (LZD), Amoxicillin, Benzathine Penicillin G
- Medical subject headings
- Syphilis, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linezolid (LZD)Drug
Ten day course. Oral Linezolid dosed at 10mg/kg twice a day.
AmoxicillinDrug
Ten day course. Oral Amoxicillin dosed at 50mg/kg twice a day.
Benzathine Penicillin GDrug
Single IM dose 50,000iu/kg
| Study group | Role | What they receive |
|---|---|---|
| Oral Linezolid | Experimental | 10 day course of Linezolid twice a day Receives: Drug: Linezolid (LZD) |
| Oral Amoxicillin | Experimental | 10 day course of Amoxicillin twice a day Receives: Drug: Amoxicillin |
| IM Benzathine penicillin | Active comparator | Single IM dose of IM Benzathine penicillin Receives: Drug: Benzathine Penicillin G |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time above MIC in serum
Time above MIC of T. pallidum for the dosing interval in serum
Measured: From enrolment through to day 10 of the study
Time above MIC in CSF
Time above MIC in CSF throughout the dosing interval
Measured: 10 days
Adverse Events
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.
Measured: Assessed from enrolment through to 24 weeks
Secondary outcomes (3)
Clinical Outcome
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.
Measured: Enrolment through to week 24
AUC/MIC Ratio in serum
Proportion of individuals achieving an AUC/MIC ratio ≥100 in serum
Measured: Enrolment through to day 10
AUC/MIC Ratio in CSF
Proportion of individuals achieving an AUC/MIC ratio ≥100 in CSF
Measured: Enrolment through to day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2025
- Study start4 May 2026
- Primary completion31 Mar 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Syphilis, CongenitalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- University College Dublin, University of Stellenbosch, Malawi Liverpool Wellcome Programme, University of Sydney, Murdoch Childrens Research Institute, University College, London, PHPT/AMS Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University
- Responsible party
- Sponsor
- Investigators
- Michael Marks, Principal investigator, London School of Hygiene and Tropical MedicineBridget Freyne, Principal investigator, University College Dublin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06921213
- Sponsor's protocol ID
- 31732
- Acronym
- Cares-1
- Status last verified
- May 2026
- First submitted
- 25 Mar 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: At completion of the study an anonymised dataset will be deposited in an appropriate repository to facilitate sharing of IPD.