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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 249
- 试验地点
- 10
- 主要终点
- The Number of Participants With a Serological Response by Month 6.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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
- •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
排除标准
- •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.
- •*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.
研究组 & 干预措施
1
2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly on Day 1, n=280
干预措施: Benzathine Penicillin (Drug)
2
2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly weekly for three successive weeks, n=280
干预措施: Benzathine Penicillin (Drug)
结局指标
主要结局
The Number of Participants With a Serological Response by Month 6.
时间窗: 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).
次要结局
- Continuous Descriptive Statistics of Socio-epidemiologic Characterictics at Baseline Collected Via a Study-specific Questionnaire(Day 1)
- Categorical Descriptive Statistics of Participant Baseline Demographics Collected Via a Study-specific Questionnaire(Day 1)
- Continuous Descriptive Statistics of Participant Baseline Demographics Collected Via a Study-specific Questionnaire(Day 1)
- Categorical Descriptive Statistics of Sexual History at Baseline Collected Via a Study-specific Questionnaire(Day 1)
- Continuous Descriptive Statistics of Sexual History at Baseline Collected Via a Study-specific Questionnaire(Day 1)
- Categorical Descriptive Statistics of Socio-epidemiologic Characteristics at Baseline Collected Via a Study-specific Questionnaire(Day 1)
- The Number of Participants Who Receive All Assigned Doses Within the Assigned Visit Windows(Through Month 12)
- The Number of Participants Who Report Jarisch-Herxheimer Reaction Manifestations(Day 1 through Day 2)
- Categorical Descriptive Statistics of Sexual History at Week 2 Collected Via a Study-specific Questionnaire(Through week 2)
- Categorical Descriptive Statistics of Sexual History at Month 1 Collected Via a Study-specific Questionnaire(Through month 1)
- Categorical Descriptive Statistics of Sexual History at Month 6 Collected Via a Study-specific Questionnaire(Through month 6)
- Number of Participants With Serological Response by Month 6 Among Participants With or Without HIV Infection(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.(Through month 12)
- Number of Participants With Serological Response by Month 12 Among Subjects With or Without HIV Infection(Through month 12)
- Categorical Descriptive Statistics of Sexual History at Week 1 Collected Via a Study-specific Questionnaire(Through week 1)
- Categorical Descriptive Statistics of Sexual History at Month 3 Collected Via a Study-specific Questionnaire(Through month 3)
- Categorical Descriptive Statistics of Sexual History at Month 12 Collected Via a Study-specific Questionnaire(Through month 12)
- Continuous Descriptive Statistics of Sexual History at Month 1 Collected Via a Study-specific Questionnaire(Through month 1)
- Continuous Descriptive Statistics of Sexual History at Month 3 Collected Via a Study-specific Questionnaire(Through month 3)
- Continuous Descriptive Statistics of Sexual History at Month 6 Collected Via a Study-specific Questionnaire(Through month 6)
- Continuous Descriptive Statistics of Sexual History at Month 9 Collected Via a Study-specific Questionnaire(Through month 9)
- Categorical Descriptive Statistics of Sexual History at Month 9 Collected Via a Study-specific Questionnaire(Through month 9)
- Continuous Descriptive Statistics of Sexual History at Week 1 Collected Via a Study-specific Questionnaire(Through week 1)
- Continuous Descriptive Statistics of Sexual History at Week 2 Collected Via a Study-specific Questionnaire(Through week 2)
- Continuous Descriptive Statistics of Sexual History at Month 12 Collected Via a Study-specific Questionnaire(Through month 12)