Congenital Syphilis Treatment Trial (CONSISTENT) in Neonates

August 31, 2026 updated by: David Kimberlin, MD, University of Alabama at Birmingham

Congenital Syphilis Treatment Trial (CONSISTENT): Phase IV, Open-label, Randomized Controlled Trial of Amoxicillin vs. Benzathine in Neonates With Possible Congenital Syphilis

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Congenital Syphilis Treatment Trial (CONSISTENT): Phase IV, Open-label, Randomized Study of Oral Amoxicillin Twice Daily for 10 days vs Single Dose Intramuscular Benzathine Penicillin G in Infants with Possible Congenital Syphilis.

The Congenital Syphilis Treatment Trial (CONSISTENT) is a Phase IV, Open-label, Randomized Study of Oral (PO) Amoxicillin Twice Daily for 10 days vs Single Dose Intramuscular (IM) Benzathine Penicillin G (BPG) in Infants with Possible Congenital Syphilis (CS). It is designed as a multicenter, US, non-inferiority trial to test the treatment efficacy of amoxicillin PO compared with the standard of care BPG IM for possible CS. Infants will be eligible to participate based on active maternal syphilis diagnosed during pregnancy with inadequate maternal treatment and a negative complete neonatal evaluation including physical exam, CSF indices including negative VDRL, radiology (xray), and bloodwork for active syphilis in the first days after birth. The participants will be randomized with block randomization by site in a 1:1 manner to receive oral amoxicillin for 10 days or IM BPG once.

Samples for pharmacologic testing will be collected on a subgroup who choose to participate in an optional pharmacokinetic substudy to measure amoxicillin and BPG concentrations; participating infants in both arms will have plasma samples collected during the first 48 hours and at 10 days. Pre-treatment and post-treatment swabs will be taken from the oropharyngeal and nasal mucosal surfaces at day 1 and day 10 to detect the presence of T. pallidum using quantitative PCR, in addition to standard serologic syphilis antibody testing with quantitative rapid plasma reagin (RPR). Additional follow up visits will occur at days 60 and 180, with serum collected to assess the primary endpoint of serologic treatment response compared with baseline

Study Type

Interventional

Enrollment (Estimated)

374

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
        • Contact:
        • Principal Investigator:
          • David Kimberlin, MD
        • Principal Investigator:
          • Jodie Dionne, MD
      • Mobile, Alabama, United States, 36617
        • University of South Alabama Medical Center
        • Principal Investigator:
          • Manimaran Ramani, MD
        • Contact:
    • California
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
        • Contact:
        • Principal Investigator:
          • Negar Ashouri, MD
    • Florida
      • Tampa, Florida, United States, 33606
        • University of South Florida
        • Contact:
        • Principal Investigator:
          • Claudia Espinosa, MD
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • LSU Health Sciences Center-Shrevport
        • Contact:
        • Principal Investigator:
          • Patricia Pichilingue-Reto, MD
    • Missouri
      • St Louis, Missouri, United States, 63310
        • Washington University-St.Louis
        • Contact:
        • Principal Investigator:
          • Carol Kao, MD
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico
        • Contact:
        • Principal Investigator:
          • Martha Muller, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
        • Contact:
        • Principal Investigator:
          • Torsten Joerger, MD
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera McKennan University Health Center
        • Principal Investigator:
          • Peter Lim, MD
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas-Southwestern Medical Center at Dallas
        • Contact:
        • Principal Investigator:
          • Amanda Evans, MD
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine-Texas Children's Hospital
        • Contact:
        • Principal Investigator:
          • Ryan Rochat, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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)
  2. Inadequate therapy (non-BPG regimen, incomplete regimen for stage, <30 days prior to delivery), undocumented therapy, or lack of maternal syphilis therapy in pregnancy
  3. Infant age ≤ 30 days old
  4. Gestational age at birth ≥35 weeks
  5. Infant birth weight ≥ 750 grams
  6. Infant tolerating oral feeds
  7. Normal infant examination, laboratory, and radiographic evaluation: hemoglobin, platelet count, CSF (cell count, protein, VDRL), long-bone radiographs
  8. Infant quantitative RPR reactive and ≤ 4-fold lower titer compared with maternal RPR
  9. Parent(s) or legal guardian(s) capable and willing to provide informed consent

Exclusion Criteria:

  1. Infant receipt of antibiotics between birth and enrollment with activity against T. pallidum (including beta-lactam, cephalosporin, or azithromycin)
  2. 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.
  3. Unable to ensure infant follow up through six months of age

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Single Dose of BPG
Neonates will receive a single dose of BPG as standard of care.
Drug: Benzathine Penicillin
Standard of Care Treatment
Other Names:
  • BPG
Experimental: Study Medication (Amoxicillin)
Neonates will receive Amoxicillin (Study Medication), twice a day for 10 days.
Drug: Amoxicillin
Amoxicillin given by mouth for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants demonstrating a treatment efficacy of oral Amoxicillin BID X 10 days vs. BPG IM X1 by 6 months of age
Time Frame: 6 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportions of participants demonstrating a treatment efficacy
Time Frame: 6 months
Serologic response defined as RPR titer reversion to non-reactive or a four-fold decline in titer at six months.
6 months
Rate of infant treatment response according to maternal syphilis stage (early/late).
Time Frame: 30 days
Stratify infant treatment response according to dichotomized maternal syphilis stage (early/late) at the time of infant delivery.
30 days
Rate of infant treatment response according to the timing of maternal syphilis treatment.
Time Frame: 30 days
Stratify infant treatment response according to timing of maternal treatment (within 30 d of delivery).
30 days
Rate of infant treatment response according to the type of treatment received by the mother during pregnancy.
Time Frame: 30 days
Stratify infant treatment response according to type of treatment (BPG/non BPG).
30 days
Rate of Infant treatment response according to maternal HIV Status.
Time Frame: 30 days
Stratify infant treatment response according to maternal HIV status.
30 days
Compare the incidence and manifestations of the Jarisch-Herxheimer reaction (JHR) among infants after amoxicillin vs BPG treatment for possible CS
Time Frame: 24 hours
Proportion of infants with JHR symptoms within 12-24 hours after the first dose of medication (amoxicillin or penicillin) with additional symptoms by self-report.
24 hours
Incidence of Treatment-Emergent Adverse Events
Time Frame: 40 days
Incidence of Treatment-Emergent Adverse Events reported as moderate and severe AEs
40 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alabama at Birmingham

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Jodie Dionne, MD, University of Alabama at Birmingham
  • Principal Investigator: David Kimberlin, MD, University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 1, 2026

Primary Completion (Estimated)

May 1, 2031

Study Completion (Estimated)

August 31, 2031

Study Registration Dates

First Submitted

February 25, 2026

First Submitted That Met QC Criteria

March 3, 2026

First Posted (Actual)

March 9, 2026

Study Record Updates

Last Update Posted (Actual)

September 2, 2026

Last Update Submitted That Met QC Criteria

August 31, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CONSISTENT
  • Pending (Other Grant/Funding Number: National Institutes of Allery and Infectious Diseases)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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