Congenital Syphilis Treatment Trial (CONSISTENT): Phase IV, Open-label, Randomized Controlled Trial of Amoxicillin vs. Benzathine in Neonates With Possible Congenital Syphilis
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 374
- 试验地点
- 11
- 主要终点
- Proportion of participants demonstrating a treatment efficacy of oral Amoxicillin BID X 10 days vs. BPG IM X1 by 6 months of age
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 0 Days 至 30 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Single Dose of BPG
Neonates will receive a single dose of BPG as standard of care.
干预措施: Benzathine Penicillin (Drug)
Study Medication (Amoxicillin)
Neonates will receive Amoxicillin (Study Medication), twice a day for 10 days.
干预措施: Amoxicillin (Drug)
结局指标
主要结局
Proportion of participants demonstrating a treatment efficacy of oral Amoxicillin BID X 10 days vs. BPG IM X1 by 6 months of age
时间窗: 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.
次要结局
- 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)
- Compare the incidence and manifestations of the Jarisch-Herxheimer reaction (JHR) among infants after amoxicillin vs BPG treatment for possible CS(24 hours)
- Incidence of Treatment-Emergent Adverse Events(40 days)
研究者
David Kimberlin, MD
Principal Investigator
University of Alabama at Birmingham