Improvement of PPROM Management With Prophylactic Antimicrobial Therapy
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 3
- 主要终点
- Latency
研究概览
简要总结
To conduct an unblinded pragmatic randomized controlled trial (pRCT) "Improvement of PPROM Management with Prophylactic Antimicrobial Therapy (iPROMPT)" of a seven-day course of ceftriaxone, clarithromycin, and metronidazole versus the current standard of care of a seven-day course of ampicillin/amoxicillin and azithromycin or erythromycin to prolong pregnancy and decrease adverse perinatal outcomes among hospitalized pregnant individuals undergoing expectant management of PPROM <34 weeks.
详细描述
Preterm prelabor rupture of membranes (PPROM) is the most common identifiable risk factor associated with preterm birth and affects 1 in 3 pregnant individuals in the United States with spontaneous preterm birth. Individuals diagnosed with PPROM who meet criteria for expectant management are currently admitted to the hospital for observation until delivery, which is generally recommended at 34 weeks' gestation unless indicated sooner. Initially upon admission, a course of prophylactic antibiotics is administered as this has been shown to prolong pregnancy and improve neonatal outcomes. The standard antibiotic regimen, primarily based on data published in 1997, includes ampicillin followed by amoxicillin with erythromycin or azithromycin for a total of 7 days. Ongoing studies are needed to determine the optimal prophylactic antibiotic regimen given changes in bacterial sensitivities over time, lack of adequate coverage for common organisms including genital mycoplasma, inadequate placental transfer of currently used antibiotic agents, ineffective antibiotic response at reducing the fetal inflammatory response, and new promising antibiotic agents that address these limitations. A promising expanded-spectrum alternative regimen with proof-of-concept is ceftriaxone, clarithromycin, and metronidazole. Observational studies have shown successful eradication of intraamniotic inflammation/infection using this new regimen. This regimen offers multiple potential advantages, including: higher bioavailability, higher transplacental transfer, and effectiveness against genital mycoplasma (clarithromycin), greater anaerobic coverage (metronidazole), and a longer half-life and expanded coverage against gram-negative bacteria (ceftriaxone) compared with the current standard regimen.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Admitted to the inpatient unit for expectant management of PPROM until delivery
- •Age ≥ 18 years with the ability to provide informed consent
- •Gestational age between 23 0/7 and 32 6/7 weeks
排除标准
- •Having received more than one dose of any prophylactic antibiotic
- •Suspected or confirmed infection requiring treatment with antibiotics
- •Allergy or contraindication to an antibiotic in either arm
- •Maternal immunosuppression
研究组 & 干预措施
Intervention group
Participants randomized to the intervention group will receive the following regimen:
- Ceftriaxone 1 g IV q 24 hours x 7 days
- Clarithromycin 500 mg PO BID x 7 days
- Metronidazole 500 mg PO q 12 hours x 7 days
干预措施: Ceftriaxone 1000 MG (Drug)
Intervention group
Participants randomized to the intervention group will receive the following regimen:
- Ceftriaxone 1 g IV q 24 hours x 7 days
- Clarithromycin 500 mg PO BID x 7 days
- Metronidazole 500 mg PO q 12 hours x 7 days
干预措施: Clarithromycin 500mg (Drug)
Intervention group
Participants randomized to the intervention group will receive the following regimen:
- Ceftriaxone 1 g IV q 24 hours x 7 days
- Clarithromycin 500 mg PO BID x 7 days
- Metronidazole 500 mg PO q 12 hours x 7 days
干预措施: Metronidazole 500 mg (Drug)
Standard of care
Participants randomized to the standard care group will receive the following regimen:
- Ampicillin 2 g IV q 6 hours x 48 hours followed by amoxicillin 250 mg q 8 hours for an additional 5 days
- Azithromycin 1 g PO x 1 dose OR erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days
干预措施: Ampicillin 2 GM Injection (Drug)
Standard of care
Participants randomized to the standard care group will receive the following regimen:
- Ampicillin 2 g IV q 6 hours x 48 hours followed by amoxicillin 250 mg q 8 hours for an additional 5 days
- Azithromycin 1 g PO x 1 dose OR erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days
干预措施: Amoxicillin 250 MG (Drug)
Standard of care
Participants randomized to the standard care group will receive the following regimen:
- Ampicillin 2 g IV q 6 hours x 48 hours followed by amoxicillin 250 mg q 8 hours for an additional 5 days
- Azithromycin 1 g PO x 1 dose OR erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days
干预措施: Azithromycin (Drug)
Standard of care
Participants randomized to the standard care group will receive the following regimen:
- Ampicillin 2 g IV q 6 hours x 48 hours followed by amoxicillin 250 mg q 8 hours for an additional 5 days
- Azithromycin 1 g PO x 1 dose OR erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days
干预措施: Erythromycin (Drug)
结局指标
主要结局
Latency
时间窗: From randomization to delivery
Latency will be measured in hours, and also reported as days for clinical interpretability.
次要结局
- Endometritis(From birth to up to 6 weeks postpartum)
- Individual clinical infections(From birth to up to 6 weeks postpartum)
- Neonatal outcome composite checklist(From birth to up to 6 weeks postpartum)
- Surgical site infection(From birth to up to 6 weeks postpartum)
- Puerperal fever(From birth to up to 6 weeks postpartum)
- Antibiotic receipt postpartum(From birth to up to 6 weeks postpartum)
- Adverse events(From randomization to delivery)
- Histopathologic chorioamnionitis/funisitis on histologic placental evaluation(From randomization to delivery)
研究者
Kartik K Venkatesh
Principal Investigator
Ohio State University