SyphilisPhase 4NCT03637660
Phase 4 Comparative Trial of Benzathine Penicillin G for Treatment of Early Syphilis in Subjects With or Without HIV Infection
A Phase 4 study testing Benzathine Penicillin in people with Syphilis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
Trial summary
This is a phase 4, randomized, open-label, multicenter trial to evaluate the efficacy of a single injected dose of Benzathine Penicillin G (BPG) 2.4 MU (Arm 1) compared to three successive weekly injected doses of BPG 2.4 MU (Arm 2) for treatment of early syphilis in human immunodeficiency virus (HIV)-infected and… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Syphilis
- What is being tested?
- Benzathine Penicillin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 249 participants
- Where
- 10 sitesUnited States
- Study dates
- 31 Oct 2018to 20 Mar 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is aged 18 years or older.
- Subject has provided informed consent.
- Subject has untreated primary*, secondary, or early latent* syphilis.
- Primary syphilis is characterized by the presence of an ulcerative lesion at a potential site of inoculation (while classically solitary, shallow, painless and with an indurated, clean base, primary lesions may be multiple, may vary considerably in appearance, and/or may not be painless) or by darkfield, acceptable polymerase chain reaction (PCR), or direct fluorescence antibody-T. pallidum (DFA-TP) positive ulcers.
- Secondary syphilis is characterized by classical palmar/plantar rash, condylomata lata, mucous patches, etc. or by darkfield, acceptable PCR, or DFA-TP positive lesions.
- Early latent syphilis is characterized by current reactive serologic tests for syphilis (STS) and a documented non-reactive STS, or documented sexual exposure to an individual known to have primary, secondary, or early latent syphilis diagnosed within the last 12 months.
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- Subject either has a newly reactive non-treponemal test (such as an RPR test) or a history of syphilis and a current increase in RPR titer of two or more dilutions (i.e., four-fold).
- If subject is of childbearing potential, subject has a negative urine or serum pregnancy test.
- Subject is willing to have an human immunodeficiency virus (HIV) test, participate in HIV counseling, and return to clinic for follow-up.
- In the opinion of the investigator, subject is able and willing to comply with study procedures, including receipt of three Benzathine Penicillin G (BPG) injected doses if randomized to Arm 2.
- If female, subject must be of non-childbearing potential* or must be using an acceptable method of birth control** to avoid becoming pregnant.
- Non-childbearing potential is defined as being post-menopausal for at least 1 year, status after bilateral tubal ligation, or status after bilateral oophorectomy, or status after hysterectomy.
- Subject must agree to avoid becoming pregnant by using one of the following acceptable methods of birth control for the entire duration of participation in the trial:
- Intrauterine contraceptive device; OR
- Oral contraceptives; OR
- Hormonal injections; OR
- Hormonal implants; OR
- Contraceptive patches; OR
- Monogamous relationship with vasectomized partner; OR
- Exclusively same-sex relationships; OR
- Use of condoms by the male partner; OR
- Abstinence
Who cannot join
- Subject previously enrolled in this trial.
- Subject has latent syphilis of unknown duration, late latent syphilis, or evidence of neurosyphilis, including ocular syphilis.*
- e.g., eye pain/redness, recent ocular change, and/or changes in visual acuity
- Subject has a known or suspected allergy or hypersensitivity to penicillin or other beta-lactam antibiotics.
- Subject has a known or suspected sexually transmitted infection (STI) other than syphilis requiring treatment with a drug active against T. pallidum.
- Subject has used antibiotics* active against T. pallidum in the preceding 30 days.
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- Note: the use of antimicrobials known to NOT be effective against T. pallidum (e.g., quinolones, sulfonamides, trimethoprim, metronidazole, spectinomycin) will be allowed.
- Subject has suspected or known ongoing drug use that might interfere with study participation and follow-up treatment.
- Subject is breastfeeding.
- Subject has used an investigational drug in the past 30 days that might interfere with safety or efficacy assessment.
- If the subject has used any investigational drugs in the past 30 days, contact the Principal Investigator, Division of Microbiology and Infectious Diseases (DMID) Clinical Project Manager, DMID Medical Officer, and FHI 360 to confirm eligibility.
- Subject has any other condition that, in the opinion of the investigator, would interfere with participation in the study.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Emory University Hospital Midtown - Emory Clinic Infectious Diseases
Atlanta, Georgia, 30308
Johns Hopkins Bayview Medical Center - Infectious Diseases
Baltimore, Maryland, 21224
University of Alabama at Birmingham School of Medicine - Infectious Disease
Birmingham, Alabama, 35294
Fenway Health - The Fenway Institute
Boston, Massachusetts, 02115
University of North Carolina School of Medicine - Center for Infectious Diseases
Durham, North Carolina, 27701-3720
Indiana University School of Medicine - Infectious Diseases
Indianapolis, Indiana, 46202
Louisiana State University Health Sciences Center
New Orleans, Louisiana, 70119
Magee Women's Hospital of UPMC - Reproductive Infectious Disease Research
Pittsburgh, Pennsylvania, 15213
University of Washington - Harborview Medical Center - Center for AIDS and STD
Seattle, Washington, 98104-2433
Wake Forest Baptist Health - Infectious Diseases
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase 4 Comparative Trial of Benzathine Penicillin G 2.4 Million Units Administered as a Single Dose Versus Three Successive Weekly Doses for Treatment of Early Syphilis in Subjects With or Without HIV Infection
This is a phase 4, randomized, open-label, multicenter trial to evaluate the efficacy of a single injected dose of Benzathine Penicillin G (BPG) 2.4 MU (Arm 1) compared to three successive weekly injected doses of BPG 2.4 MU (Arm 2) for treatment of early syphilis in human immunodeficiency virus (HIV)-infected and HIV-uninfected subjects. The study will enroll 560 adults (to achieve 420 evaluable subjects) aged 18 years or older with untreated early syphilis (primary, secondary, or early latent). It will be conducted at 9 sites in the US and last for 48 months with patient participation duration of 12 months. The primary objective is to compare the serological response to therapy in subjects with early (primary, secondary, or early latent) syphilis treated with Benzathine Penicillin G (BPG) 2.4 million units (MU) once or weekly for three successive weeks.
Read the detailed description
This is a phase 4, randomized, open-label, multicenter trial to evaluate the efficacy of a single injected dose of Benzathine Penicillin G (BPG) 2.4 MU (Arm 1) compared to three successive weekly injected doses of BPG 2.4 MU (Arm 2) for treatment of early syphilis in human immunodeficiency virus (HIV)-infected and HIV-uninfected subjects. The study will enroll 560 adults (to achieve 420 evaluable subjects) aged 18 years or older with untreated early syphilis (primary, secondary, or early latent). It will be conducted at 9 sites in the US and last for 48 months with patient participation duration of 12 months. The primary objective is to compare the serological response to therapy in subjects with early (primary, secondary, or early latent) syphilis treated with Benzathine Penicillin G (BPG) 2.4 million units (MU) once or weekly for three successive weeks. The secondary objectives are: 1) to determine if the difference in response to therapy between treatment arms by Month 6 differs among subjects with or without HIV infection; 2) to determine the impact of multiple BPG injected doses on subject compliance with study product and adherence to the corresponding scheduled visits; 3) to determine the incidence and manifestations of the Jarisch-Herxheimer reaction among subjects treated for early syphilis with BPG; 4) to collect prospective data up to Month 12 on the serological response to therapy in subjects treated for early syphilis with either BPG regimen; 5) to compare epidemiological characteristics of early syphilis among subjects with or without HIV infection.
- Conditions
- Syphilis
- Being tested
- Benzathine Penicillin
- Keywords
- Benzathine penicillin G, Early Syphillis, HIV, Phase 4
- Medical subject headings
- Syphilis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Benzathine PenicillinDrug
BPG will be administered as a deep intramuscular injection in the upper, outer quadrant of the buttock.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly on Day 1, n=280 Receives: Drug: Benzathine Penicillin |
| 2 | Experimental | 2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly weekly for three successive weeks, n=280 Receives: Drug: Benzathine Penicillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants With a Serological Response by Month 6.
Serological response to therapy by Month 6 was defined as follows, where available rapid plasma reagin (RPR) results from all visits prior to the end of the Month 6 visit window (i.e., scheduled visits up to and including the Month 6 visit, early termination visit, or any unscheduled visit that occurred prior to the end of month 6 visit window) were evaluated:
- 4-fold or greater decline in RPR titer at any visit prior to the end of the Month 6 visit window compared to baseline, OR
- RPR-negative at any visit prior to the end of the Month 6 visit window (i.e., seroreversion).
Measured: Day 1 to Day 180
Secondary outcomes (25)
Categorical Descriptive Statistics of Sexual History at Baseline Collected Via a Study-specific Questionnaire
Gender identity, sexual orientation, sexual partner, sex history in last 60 days
Measured: Day 1
Continuous Descriptive Statistics of Sexual History at Baseline Collected Via a Study-specific Questionnaire
Sex history in last 60 days
Measured: Day 1
Categorical Descriptive Statistics of Socio-epidemiologic Characteristics at Baseline Collected Via a Study-specific Questionnaire
Highest level of education completed, stage of syphilis, prior syphilis history
Measured: Day 1
Continuous Descriptive Statistics of Socio-epidemiologic Characterictics at Baseline Collected Via a Study-specific Questionnaire
Years of formal education
Measured: Day 1
Categorical Descriptive Statistics of Participant Baseline Demographics Collected Via a Study-specific Questionnaire
Sex, Ethnicity, Race
Measured: Day 1
Continuous Descriptive Statistics of Participant Baseline Demographics Collected Via a Study-specific Questionnaire
Age
Measured: Day 1
The Number of Participants Who Receive All Assigned Doses Within the Assigned Visit Windows
Compliance with study product will be defined as the participant received all assigned doses within the assigned visit windows. A participant is not adherent to study product if they miss at least one dose or receive at least one dose out of the visit window.
Measured: Through Month 12
The Number of Participants Who Report Jarisch-Herxheimer Reaction Manifestations
Approximately 24 hours after Visit 1, participants were contacted and evaluated for symptoms of a JHR, which included fever, chills, myalgia, weakness, flushing, worsening of skin rash, tachycardia, heart palpitations, arthralgia, nausea, headache, and dizziness, including time of onset and time of resolution of each symptom reported.
Measured: Day 1 through Day 2
Number of Participants With Serological Response by Month 6 Among Participants With or Without HIV Infection
Serological response to therapy by Month 6 was defined as follows, where available rapid plasma reagin (RPR) results from all visits prior to the end of the Month 6 visit window (i.e., scheduled visits up to and including the Month 6 visit, early termination visit, or any unscheduled visit that occurred prior to the end of month 6 visit window) were evaluated:
- 4-fold or greater decline in RPR titer at any visit prior to the end of the Month 6 visit window compared to baseline, OR
- RPR-negative at any visit prior to the end of the Month 6 visit window (i.e., seroreversion).
Serological response to therapy by Month 6 was examined among participants with and without HIV infection,
Measured: Day 1 to Day 180
Number of Participants With Serological Response (Defined as Either a 4-fold or Greater Decline in Rapid Plasma Regain (RPR) Titer Compared to Baseline or Being Rapid Plasma Regain -Negative [Seroreversion]) by Month 12.
Serological response to therapy by Month 12 was defined as follows, where available rapid plasma reagin (RPR) results from all visits prior to the end of the Month 12 visit window (i.e., scheduled visits up to and including the Month 12 visit, early termination visit, or any unscheduled visit that occurred prior to the end of month 12 visit window) were evaluated:
- 4-fold or greater decline in RPR titer at any visit prior to the end of the Month 12 visit window compared to baseline, OR
- RPR-negative at any visit prior to the end of the Month 12 visit window (i.e., seroreversion).
Measured: Through month 12
Number of Participants With Serological Response by Month 12 Among Subjects With or Without HIV Infection
Serological response to therapy by Month 12 was defined as follows, where available rapid plasma reagin (RPR) results from all visits prior to the end of the Month 12 visit window (i.e., scheduled visits up to and including the Month 12 visit, early termination visit, or any unscheduled visit that occurred prior to the end of month 6 visit window) were evaluated:
- 4-fold or greater decline in RPR titer at any visit prior to the end of the Month 12 visit window compared to baseline, OR
- RPR-negative at any visit prior to the end of the Month 12visit window (i.e., seroreversion).
Serological response to therapy by Month 12 was examined among participants with and without HIV infection,
Measured: Through month 12
Categorical Descriptive Statistics of Sexual History at Week 1 Collected Via a Study-specific Questionnaire
Sex history since last visit.
Measured: Through week 1
Categorical Descriptive Statistics of Sexual History at Week 2 Collected Via a Study-specific Questionnaire
Sex history since last visit.
Measured: Through week 2
Categorical Descriptive Statistics of Sexual History at Month 1 Collected Via a Study-specific Questionnaire
Sex history since last visit.
Measured: Through month 1
Categorical Descriptive Statistics of Sexual History at Month 3 Collected Via a Study-specific Questionnaire
Sex history since last visit.
Measured: Through month 3
Categorical Descriptive Statistics of Sexual History at Month 6 Collected Via a Study-specific Questionnaire
Sex history since last visit.
Measured: Through month 6
Categorical Descriptive Statistics of Sexual History at Month 9 Collected Via a Study-specific Questionnaire
Sex history since last visit.
Measured: Through month 9
Categorical Descriptive Statistics of Sexual History at Month 12 Collected Via a Study-specific Questionnaire
Sex history since last visit.
Measured: Through month 12
Continuous Descriptive Statistics of Sexual History at Week 1 Collected Via a Study-specific Questionnaire
Sex history since last visit
Measured: Through week 1
Continuous Descriptive Statistics of Sexual History at Week 2 Collected Via a Study-specific Questionnaire
Sex history since last visit
Measured: Through week 2
Continuous Descriptive Statistics of Sexual History at Month 1 Collected Via a Study-specific Questionnaire
Sex history since last visit
Measured: Through month 1
Continuous Descriptive Statistics of Sexual History at Month 3 Collected Via a Study-specific Questionnaire
Sex history since last visit
Measured: Through month 3
Continuous Descriptive Statistics of Sexual History at Month 6 Collected Via a Study-specific Questionnaire
Sex history since last visit
Measured: Through month 6
Continuous Descriptive Statistics of Sexual History at Month 9 Collected Via a Study-specific Questionnaire
Sex history since last visit
Measured: Through month 9
Continuous Descriptive Statistics of Sexual History at Month 12 Collected Via a Study-specific Questionnaire
Sex history since last visit
Measured: Through month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2018
- Study start31 Oct 2018
- Primary completion7 Sep 2022
- Study completion20 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SyphilisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 249 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03637660
- Sponsor's protocol ID
- 17-0101
- Status last verified
- 19 Sep 2019
- First submitted
- 16 Aug 2018
- Last updated
- 14 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hook EW 3rd, Dionne JA, Workowski K, McNeil CJ, Taylor SN, Batteiger TA, Dombrowski JC, Mayer KH, Sena AC, Hamill MM, Wiesenfeld HC, Zhu C, Perlowski C, Mejia-Galvis JE, Newman LM. One Dose versus Three Doses of Benzathine Penicillin G in Early Syphilis. N Engl J Med. 2025 Sep 4;393(9):869-878. doi: 10.1056/NEJMoa2401802.
PubMed 40902161Dionne JA, Zhu C, Mejia-Galvis J, Workowski K, Batteiger TA, Dombrowski JC, Mayer KH, McNeil CJ, Sena AC, Taylor S, Wiesenfeld HC, Hamill MM, Perlowski C, Hook EW 3rd. Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment in Adults With Early Syphilis: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025 Feb 3;8(2):e2459490. doi: 10.1001/jamanetworkopen.2024.59490.
PubMed 39946129Dionne JA, Giacani L, Tamhane A, Workowski K, Lieberman NAP, Greninger AL, Perlowski C, Newman L, Hook EW 3rd. Prevalence and Predictors of Oral Treponema pallidum Detection by Quantitative Polymerase Chain Reaction in Early Syphilis. J Infect Dis. 2024 Jun 14;229(6):1628-1636. doi: 10.1093/infdis/jiad582.
PubMed 38124508Dionne-Odom J, Workowski K, Perlowski C, Taylor SN, Mayer KH, McNeil CJ, Hamill MM, Dombrowski JC, Batteiger TA, Sena AC, Wiesenfeld HC, Newman L, Hook EW 3rd. Coinfection With Chlamydial and Gonorrheal Infection Among US Adults With Early Syphilis. Sex Transm Dis. 2022 Aug 1;49(8):e87-e89. doi: 10.1097/OLQ.0000000000001605. Epub 2022 Jan 24.
PubMed 35067599
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4 Comparative Trial of Benzathine Penicillin G 2.4 Million Units Administered as a Single Dose Versus Three Successive Weekly Doses for Treatment of Early Syphilis in Subjects With or Without HIV Infection
- ClinicalTrials.gov ID
- NCT03637660
- Acronym / sponsor ID
- 17-0101
- Conditions
- Syphilis
- Keywords
- Benzathine penicillin G, Early Syphillis, HIV, Phase 4
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 249 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 31 Oct 2018 (actual)
- Primary completion
- 7 Sep 2022 (actual)
- Study completion
- 20 Mar 2023 (actual)
- First posted
- 20 Aug 2018 (actual)
- Results
- Posted 26 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 4, randomized, open-label, multicenter trial to evaluate the efficacy of a single injected dose of Benzathine Penicillin G (BPG) 2.4 MU (Arm 1) compared to three successive weekly injected doses of BPG 2.4 MU (Arm 2) for treatment of early syphilis in human immunodeficiency virus (HIV)-infected and HIV-uninfected subjects. The study will enroll 560 adults (to achieve 420 evaluable subjects) aged 18 years or older with untreated early syphilis (primary, secondary, or early latent). It will be conducted at 9 sites in the US and last for 48 months with patient participation duration of 12 months. The primary objective is to compare the serological response to therapy in subjects with early (primary, secondary, or early latent) syphilis treated with Benzathine Penicillin G (BPG) 2.4 million units (MU) once or weekly for three successive weeks.
Detailed description
This is a phase 4, randomized, open-label, multicenter trial to evaluate the efficacy of a single injected dose of Benzathine Penicillin G (BPG) 2.4 MU (Arm 1) compared to three successive weekly injected doses of BPG 2.4 MU (Arm 2) for treatment of early syphilis in human immunodeficiency virus (HIV)-infected and HIV-uninfected subjects. The study will enroll 560 adults (to achieve 420 evaluable subjects) aged 18 years or older with untreated early syphilis (primary, secondary, or early latent). It will be conducted at 9 sites in the US and last for 48 months with patient participation duration of 12 months. The primary objective is to compare the serological response to therapy in subjects with early (primary, secondary, or early latent) syphilis treated with Benzathine Penicillin G (BPG) 2.4 million units (MU) once or weekly for three successive weeks. The secondary objectives are: 1) to determine if the difference in response to therapy between treatment arms by Month 6 differs among subjects with or without HIV infection; 2) to determine the impact of multiple BPG injected doses on subject compliance with study product and adherence to the corresponding scheduled visits; 3) to determine the incidence and manifestations of the Jarisch-Herxheimer reaction among subjects treated for early syphilis with BPG; 4) to collect prospective data up to Month 12 on the serological response to therapy in subjects treated for early syphilis with either BPG regimen; 5) to compare epidemiological characteristics of early syphilis among subjects with or without HIV infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Benzathine Penicillin2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly on Day 1, n=280 |
| 2 | Experimental | Drug: Benzathine Penicillin2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly weekly for three successive weeks, n=280 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Subject is aged 18 years or older.
- Subject has provided informed consent.
- Subject has untreated primary*, secondary, or early latent* syphilis.
- Primary syphilis is characterized by the presence of an ulcerative lesion at a potential site of inoculation (while classically solitary, shallow, painless and with an indurated, clean base, primary lesions may be multiple, may vary considerably in appearance, and/or may not be painless) or by darkfield, acceptable polymerase chain reaction (PCR), or direct fluorescence antibody-T. pallidum (DFA-TP) positive ulcers.
- Secondary syphilis is characterized by classical palmar/plantar rash, condylomata lata, mucous patches, etc. or by darkfield, acceptable PCR, or DFA-TP positive lesions.
Key exclusion criteria (12 listed)
- Subject previously enrolled in this trial.
- Subject has latent syphilis of unknown duration, late latent syphilis, or evidence of neurosyphilis, including ocular syphilis.*
- e.g., eye pain/redness, recent ocular change, and/or changes in visual acuity
- Subject has a known or suspected allergy or hypersensitivity to penicillin or other beta-lactam antibiotics.
- Subject has a known or suspected sexually transmitted infection (STI) other than syphilis requiring treatment with a drug active against T. pallidum.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Benzathine PenicillinBPG will be administered as a deep intramuscular injection in the upper, outer quadrant of the buttock. | Drug | 1, 2 |
Primary outcome
The Number of Participants With a Serological Response by Month 6.
Time frame: Day 1 to Day 180
Serological response to therapy by Month 6 was defined as follows, where available rapid plasma reagin (RPR) results from all visits prior to the end of the Month 6 visit window (i.e., scheduled visits up to and including the Month 6 visit, early termination visit, or any unscheduled visit that occurred prior to the end of month 6 visit window) were evaluated: * 4-fold or greater decline in RPR titer at any visit prior to the end of the Month 6 visit window compared to baseline, OR * RPR-negative at any visit prior to the end of the Month 6 visit window (i.e., seroreversion).
25 secondary outcomes
Categorical Descriptive Statistics of Sexual History at Baseline Collected Via a Study-specific Questionnaire
Time frame: Day 1
Continuous Descriptive Statistics of Sexual History at Baseline Collected Via a Study-specific Questionnaire
Time frame: Day 1
Categorical Descriptive Statistics of Socio-epidemiologic Characteristics at Baseline Collected Via a Study-specific Questionnaire
Time frame: Day 1
Continuous Descriptive Statistics of Socio-epidemiologic Characterictics at Baseline Collected Via a Study-specific Questionnaire
Time frame: Day 1
Categorical Descriptive Statistics of Participant Baseline Demographics Collected Via a Study-specific Questionnaire
Time frame: Day 1
Continuous Descriptive Statistics of Participant Baseline Demographics Collected Via a Study-specific Questionnaire
Time frame: Day 1
The Number of Participants Who Receive All Assigned Doses Within the Assigned Visit Windows
Time frame: Through Month 12
The Number of Participants Who Report Jarisch-Herxheimer Reaction Manifestations
Time frame: Day 1 through Day 2
Number of Participants With Serological Response by Month 6 Among Participants With or Without HIV Infection
Time frame: Day 1 to Day 180
Number of Participants With Serological Response (Defined as Either a 4-fold or Greater Decline in Rapid Plasma Regain (RPR) Titer Compared to Baseline or Being Rapid Plasma Regain -Negative [Seroreversion]) by Month 12.
Time frame: Through month 12
Number of Participants With Serological Response by Month 12 Among Subjects With or Without HIV Infection
Time frame: Through month 12
Categorical Descriptive Statistics of Sexual History at Week 1 Collected Via a Study-specific Questionnaire
Time frame: Through week 1
Categorical Descriptive Statistics of Sexual History at Week 2 Collected Via a Study-specific Questionnaire
Time frame: Through week 2
Categorical Descriptive Statistics of Sexual History at Month 1 Collected Via a Study-specific Questionnaire
Time frame: Through month 1
Categorical Descriptive Statistics of Sexual History at Month 3 Collected Via a Study-specific Questionnaire
Time frame: Through month 3
Categorical Descriptive Statistics of Sexual History at Month 6 Collected Via a Study-specific Questionnaire
Time frame: Through month 6
Categorical Descriptive Statistics of Sexual History at Month 9 Collected Via a Study-specific Questionnaire
Time frame: Through month 9
Categorical Descriptive Statistics of Sexual History at Month 12 Collected Via a Study-specific Questionnaire
Time frame: Through month 12
Continuous Descriptive Statistics of Sexual History at Week 1 Collected Via a Study-specific Questionnaire
Time frame: Through week 1
Continuous Descriptive Statistics of Sexual History at Week 2 Collected Via a Study-specific Questionnaire
Time frame: Through week 2
Continuous Descriptive Statistics of Sexual History at Month 1 Collected Via a Study-specific Questionnaire
Time frame: Through month 1
Continuous Descriptive Statistics of Sexual History at Month 3 Collected Via a Study-specific Questionnaire
Time frame: Through month 3
Continuous Descriptive Statistics of Sexual History at Month 6 Collected Via a Study-specific Questionnaire
Time frame: Through month 6
Continuous Descriptive Statistics of Sexual History at Month 9 Collected Via a Study-specific Questionnaire
Time frame: Through month 9
Continuous Descriptive Statistics of Sexual History at Month 12 Collected Via a Study-specific Questionnaire
Time frame: Through month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40902161Hook EW 3rd, Dionne JA, Workowski K, McNeil CJ, Taylor SN, Batteiger TA, Dombrowski JC, Mayer KH, Sena AC, Hamill MM, Wiesenfeld HC, Zhu C, Perlowski C, Mejia-Galvis JE, Newman LM. One Dose versus Three Doses of Benzathine Penicillin G in Early Syphilis. N Engl J Med. 2025 Sep 4;393(9):869-878. doi: 10.1056/NEJMoa2401802.
- Derived from this study: PubMed 39946129Dionne JA, Zhu C, Mejia-Galvis J, Workowski K, Batteiger TA, Dombrowski JC, Mayer KH, McNeil CJ, Sena AC, Taylor S, Wiesenfeld HC, Hamill MM, Perlowski C, Hook EW 3rd. Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment in Adults With Early Syphilis: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025 Feb 3;8(2):e2459490. doi: 10.1001/jamanetworkopen.2024.59490.
- Derived from this study: PubMed 38124508Dionne JA, Giacani L, Tamhane A, Workowski K, Lieberman NAP, Greninger AL, Perlowski C, Newman L, Hook EW 3rd. Prevalence and Predictors of Oral Treponema pallidum Detection by Quantitative Polymerase Chain Reaction in Early Syphilis. J Infect Dis. 2024 Jun 14;229(6):1628-1636. doi: 10.1093/infdis/jiad582.
- Derived from this study: PubMed 35067599Dionne-Odom J, Workowski K, Perlowski C, Taylor SN, Mayer KH, McNeil CJ, Hamill MM, Dombrowski JC, Batteiger TA, Sena AC, Wiesenfeld HC, Newman L, Hook EW 3rd. Coinfection With Chlamydial and Gonorrheal Infection Among US Adults With Early Syphilis. Sex Transm Dis. 2022 Aug 1;49(8):e87-e89. doi: 10.1097/OLQ.0000000000001605. Epub 2022 Jan 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Benzathine Penicillin in people with Syphilis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Participants With a Serological Response by Month 6. (time frame: Day 1 to Day 180). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03637660, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025.