Comprehensive Ambulatory Antibiotics for the Treatment of Congenital Syphilis

NCT06921213 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 31732
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 3

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.

Conditions

Syphilis, Congenital

Outcome Measures

Primary Outcomes (3)

• Time above MIC in serum

  Time above MIC of T. pallidum for the dosing interval in serum

  From enrolment through to day 10 of the study

• Time above MIC in CSF

  Time above MIC in CSF throughout the dosing interval

  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.

  Assessed from enrolment through to 24 weeks

Secondary Outcomes (3)

• Clinical Outcome

  Enrolment through to week 24

• AUC/MIC Ratio in serum

  Enrolment through to day 10

• AUC/MIC Ratio in CSF

  Enrolment through to day 10

Study Arms (3)

Oral Linezolid

EXPERIMENTAL

10 day course of Linezolid twice a day

Drug: Linezolid (LZD)

Oral Amoxicillin

EXPERIMENTAL

10 day course of Amoxicillin twice a day

Drug: Amoxicillin

IM Benzathine penicillin

ACTIVE COMPARATOR

Single IM dose of IM Benzathine penicillin

Drug: Benzathine Penicillin G

Interventions

Linezolid (LZD) DRUG

Ten day course. Oral Linezolid dosed at 10mg/kg twice a day.

Oral Linezolid

Amoxicillin DRUG

Ten day course. Oral Linezolid dosed at 50mg/kg twice a day.

Oral Amoxicillin

Benzathine Penicillin G DRUG

Single IM dose 50,000iu/kg

IM Benzathine penicillin

Eligibility Criteria

• Age: 0 Days - 7 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• 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).
• 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.

You may not qualify if:

• \- 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.
• \. They have a birthweight \<2kg 3. They are nil by mouth. 4. They have a life-limiting congenital anomaly

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• University College Dublin: collaborator
• University of Stellenbosch: collaborator
• Malawi Liverpool Wellcome Programme: collaborator
• University of Sydney: collaborator
• Murdoch Childrens Research Institute: collaborator
• MRC CTU at UCL: collaborator
• PHPT/AMS Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University: collaborator

Study Sites (3)

Universitas Indonesia

Jakarta, Indonesia

Location

Malawi Liverpool Wellcome Programme

Blantyre, Malawi

Location

Stellenbosch

Stellenbosch, South Africa

Location

MeSH Terms

Conditions

Syphilis, Congenital

Interventions

Linezolid; Amoxicillin; Penicillin G

Condition Hierarchy (Ancestors)

Syphilis; Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ampicillin; Penicillins; beta-Lactams; Lactams; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michael Marks

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

• Bridget Freyne

  University College Dublin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Prentice

CONTACT

+4420 7636 8636; sarah.prentice@lshtm.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 10, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Following completion of the study
• Access Criteria: Data will be available via a repository to other researchers

Locations

ID (1); MA (1); ZA (1)