The University of Alabama at Birmingham has received a USD 2.34 million NIAID U01 cooperative agreement to conduct CONSISTENT, a Phase IV randomized controlled trial testing oral amoxicillin against benzathine penicillin G (BPG) for possible congenital syphilis in neonates — the first prospective head-to-head comparison of these regimens in this population.
Addressing a supply-chain vulnerability in standard of care
Congenital syphilis rates have risen across every US region over the past decade, and the current standard treatment — a single intramuscular dose of BPG — faces intermittent supply shortages that create clinical management gaps. CONSISTENT is designed to determine whether a 10-day course of oral amoxicillin (50 mg/kg twice daily) produces serologic responses non-inferior to BPG within six months of treatment, using a 10% non-inferiority margin.
The trial will enroll 374 neonates of at least 35 weeks gestational age across 12 US clinical sites over two years. Principal investigators are Jodie Dionne-Odom and David W. Kimberlin at the University of Alabama at Birmingham, based within the Children's of Alabama healthcare system.
Trial design and secondary aims
Beyond the primary efficacy comparison, the study incorporates an optional pharmacokinetic substudy in 30 participants to confirm that the 50 mg/kg amoxicillin dose maintains plasma concentrations above the established minimum inhibitory concentration of 0.42 mg/L for Treponema pallidum. A third aim evaluates quantitative PCR testing of oropharyngeal and nasal swabs as a diagnostic tool for refining the classification of possible congenital syphilis in exposed infants — a population currently defined by in-utero syphilis exposure with negative clinical and serologic evaluation.
The open-label design reflects the practical difficulty of blinding intramuscular versus oral administration in neonates, and the Phase IV designation indicates the study is evaluating an established antibiotic in a new indication and dosing context rather than a novel compound.