Syphilis, CongenitalPhase 4NCT07457385
Congenital Syphilis Treatment Trial (CONSISTENT) in Neonates
A Phase 4 study testing Benzathine Penicillin and Amoxicillin in people with Syphilis, Congenital, run by University of Alabama at Birmingham at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 30 days
- Conditions the study is for
- Syphilis, Congenital
- What is being tested?
- Benzathine Penicillin and Amoxicillin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 374 participants
- Where
- 11 sitesUnited States
- Study dates
- 1 Nov 2026to 31 Aug 2031
- Phase
- Phase 4
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 30 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites
University of New Mexico
Albuquerque, New Mexico, 87106
Martha Muller, MD, 505-272-5551, mlmuller@salud.unm.edu
Martha Muller, MD
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Jodie Dionne, MD, 205-975-6530, jdionne@uabmc.edu
David Kimberlin, MD
University of Texas-Southwestern Medical Center at Dallas
Dallas, Texas, 75390
Amanda Evans, MD, 972-567-5669, amanda.evans@utsouthwestern.edu
Amanda Evans, MD
Baylor College of Medicine-Texas Children's Hospital
Houston, Texas, 77030
Ryan Rochat, MD, 832-824-4350, rochat@bcm.edu
Ryan Rochat, MD
University of South Alabama Medical Center
Mobile, Alabama, 36617
Manimaran Ramani, MD, 251-471-7000, mramacini@health.southalabama.edu
Manimaran Ramani, MD
Children's Hospital of Orange County
Orange, California, 92868
Negar Ashouri, MD, 714-509-7024, nashouri@choc.org
Negar Ashouri, MD
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Torsten Joerger, MD, 215-435-3464, joergert@chop.edu
Torsten Joerger, MD
LSU Health Sciences Center-Shrevport
Shreveport, Louisiana, 71103
Patricia Pichilingue-Reto, MD, 318-675-7066, patricia.pichilinguereto@lsuhs.edu
Patricia Pichilingue-Reto, MD
Avera McKennan University Health Center
Sioux Falls, South Dakota, 57105
Peter Lim, MD, 605-322-3666, peter.lim@avera.org
Peter Lim, MD
Washington University-St.Louis
St Louis, Missouri, 63310
Carol Kao, MD, 314-273-4687, kaoc@wustl.edu
Carol Kao, MD
University of South Florida
Tampa, Florida, 33606
Claudia Espinosa, MD, 913-832-4946, claudiaespinosa@usf.edu
Claudia Espinosa, MD
About this study
Official title: 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.
Read the 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
- Conditions
- Syphilis, Congenital
- Being tested
- Benzathine Penicillin, Amoxicillin
- Medical subject headings
- Syphilis, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Benzathine PenicillinDrug
Also called BPG
Standard of Care Treatment
AmoxicillinDrug
Amoxicillin given by mouth for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Single Dose of BPG | Active comparator | Neonates will receive a single dose of BPG as standard of care. Receives: Drug: Benzathine Penicillin |
| Study Medication (Amoxicillin) | Experimental | Neonates will receive Amoxicillin (Study Medication), twice a day for 10 days. Receives: Drug: Amoxicillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (7)
Proportions of participants demonstrating a treatment efficacy
Serologic response defined as RPR titer reversion to non-reactive or a four-fold decline in titer at six months.
Measured: 6 months
Rate of infant treatment response according to maternal syphilis stage (early/late).
Stratify infant treatment response according to dichotomized maternal syphilis stage (early/late) at the time of infant delivery.
Measured: 30 days
Rate of infant treatment response according to the timing of maternal syphilis treatment.
Stratify infant treatment response according to timing of maternal treatment (within 30 d of delivery).
Measured: 30 days
Rate of infant treatment response according to the type of treatment received by the mother during pregnancy.
Stratify infant treatment response according to type of treatment (BPG/non BPG).
Measured: 30 days
Rate of Infant treatment response according to maternal HIV Status.
Stratify infant treatment response according to maternal HIV status.
Measured: 30 days
Compare the incidence and manifestations of the Jarisch-Herxheimer reaction (JHR) among infants after amoxicillin vs BPG treatment for possible CS
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.
Measured: 24 hours
Incidence of Treatment-Emergent Adverse Events
Incidence of Treatment-Emergent Adverse Events reported as moderate and severe AEs
Measured: 40 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 May 2031 (estimated)
- Study completion31 Aug 2031 (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.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 374 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Kimberlin, MD, University of Alabama at Birmingham
- Investigators
- David Kimberlin, MD, Principal investigator, University of Alabama at BirminghamJodie Dionne, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07457385
- Sponsor's protocol ID
- CONSISTENT
- Other IDs
- Pending
- Status last verified
- Feb 2026
- First submitted
- 25 Feb 2026
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No