Congenital Syphilis Treatment Trial (CONSISTENT) in Neonates

NCT07457385 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: CONSISTENTPending
• Study Type: interventional
• Target: 374
• Locations: 0 countries
• Sites: N/A

Brief Summary

The Investigator hypothesize that the treatment efficacy will be similar in both study arms. Secondary outcomes and endpoints will characterize safety by comparing adverse events (AEs), tolerability, and adherence to therapy in each arm. This is a Phase 4, open-label, multicenter trial designed to evaluate the efficacy of a single injected dose of intramuscular (IM) BPG (Arm 1) compared to oral amoxicillin administered twice daily (BID) for 10 days (Arm 2). The study will involve infants aged ≤ 30 days old with suspected untreated syphilis. The trial will be conducted at 12 sites across the U.S., enrolling approximately 374 participants. Upon randomization, participants will undergo baseline study sample collection (blood, oropharyngeal, and nasal mucosal swabs for PCR testing) and then receive either treatment with oral amoxicillin or IM BPG, both with directly observed therapy. The participant enrolled in the optional pharmacokinetic (PK) sub-study will have additional blood samples collected for PK analysis within the first 24-48 hours after treatment. Participants will be discharged from the hospital following routine procedures, with the oral amoxicillin dosing continued at home (BID) by the caregiver.

Conditions

Syphilis, Congenital

Outcome Measures

Primary Outcomes (1)

• Proportion of participants demonstrating a treatment efficacy of oral Amoxicillin BID X 10 days vs. BPG IM X1 by 6 months of age

  Proportion with serologic response defined as RPR titer reversion to non-reactive or a four-fold decline in titer within one to six months after treatment.

  6 months

Secondary Outcomes (7)

• Proportions of participants demonstrating a treatment efficacy

  6 months

• Rate of infant treatment response according to maternal syphilis stage (early/late).

  30 days

• Rate of infant treatment response according to the timing of maternal syphilis treatment.

  30 days

• Rate of infant treatment response according to the type of treatment received by the mother during pregnancy.

  30 days

• Rate of Infant treatment response according to maternal HIV Status.

  30 days

Study Arms (2)

Single Dose of BPG

ACTIVE COMPARATOR

Neonates will receive a single dose of BPG as standard of care.

Drug: Benzathine Penicillin

Study Medication (Amoxicillin)

EXPERIMENTAL

Neonates will receive Amoxicillin (Study Medication), twice a day for 10 days.

Drug: Amoxicillin

Interventions

Benzathine Penicillin DRUG

Standard of Care Treatment

Also known as: BPG

Single Dose of BPG

Amoxicillin DRUG

Amoxicillin given by mouth for 10 days

Study Medication (Amoxicillin)

Eligibility Criteria

• Age: 0 Days - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Confirmed staged maternal syphilis in pregnancy with rapid plasma reagin (RPR) + and T. pallidum hemagglutination antibody (TPHA) or other evidence of active syphilis (i.e. ulcerative anogenital lesion with positive darkfield microscopy or PCR+ for T. pallidum)
• Inadequate therapy (non-BPG regimen, incomplete regimen for stage, \<30 days prior to delivery), undocumented therapy, or lack of maternal syphilis therapy in pregnancy
• Infant age ≤ 30 days old
• Gestational age at birth ≥35 weeks
• Infant birth weight ≥ 750 grams
• Infant tolerating oral feeds
• Normal infant examination, laboratory, and radiographic evaluation: hemoglobin, platelet count, CSF (cell count, protein, VDRL), long-bone radiographs
• Infant quantitative RPR reactive and ≤ 4-fold lower titer compared with maternal RPR
• Parent(s) or legal guardian(s) capable and willing to provide informed consent

You may not qualify if:

• Infant receipt of antibiotics between birth and enrollment with activity against T. pallidum (including beta-lactam, cephalosporin, or azithromycin)
• Uncontrolled maternal HIV (viral load \>1000 copies/mL at or within 4 weeks of delivery) or HIV-exposed infants who require three drug antiretroviral post exposure prophylaxis.
• Unable to ensure infant follow up through six months of age

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

MeSH Terms

Conditions

Syphilis, Congenital

Interventions

Penicillin G Benzathine; Amoxicillin

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)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ampicillin

Study Officials

• David Kimberlin, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jill Griffin, MSN

CONTACT

2056352537; jillgriffin@uabmc.edu

Linda Austin

CONTACT

2056382530; lpaustin@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 9, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): August 31, 2031
• Last Updated: March 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share