Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) Trial

剖腹产最佳抗生素预防 (C/SOAP) 试验

• 批准号: 8516076
• 负责人: ALAN THEVENET N. TITA
• 金额: $ 56.65万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516076
• 关键词: Abscess; Accounting; Address; Adverse effects; Alabama; Allergic; Amniotic Fluid; Antibiotic Prophylaxis; Antibiotics; Azithromycin; Bacteremia; Bacteria; Biological; Bronchopulmonary Dysplasia; Cefazolin; Centers for Disease Control and Prevention (U.S.); Cephalosporins; Cesarean section; Cessation of life; Clindamycin; Clinical Trials Design; Conduct Clinical Trials; Data; Discipline of obstetrics; Dose; Effectiveness; Emergency Situation; Endometritis; Enrollment; Exposure to; Face; Frequencies; Future; Genital system; Healthcare; High Risk Woman; Human; Hypersensitivity; Incidence; Individual; Infection; Intravenous; Length of Stay; Medical; Membrane; Microbe; Morbidity - disease rate; Mothers; Multi-Institutional Clinical Trial; Mycoplasma; Neonatal; Newborn Infant; North Carolina; Operative Surgical Procedures; Organism; Outcome; Perinatal; Perinatal Exposure; Pharmaceutical Preparations; Placebos; Pneumonia; Postpartum Period; Pregnancy; Premature Infant; Prophylactic treatment; Publishing; Pyloric Stenosis; Randomized; Randomized Clinical Trials; Reaction; Recommendation; Regimen; Relative (related person); Research Personnel; Resistance; Resources; Risk; Risk Factors; Rupture; Safety; Schedule; Sepsis; Sepsis Syndrome; Site; Specimen; Surgical incisions; Texas; Thrombosis; Umbilical Cord Blood; Umbilical cord structure; Universities; Ureaplasma; Vaginal delivery procedure; Woman; Wound Infection; base; comparative effectiveness; cost effective; experience; fetal; innovation; pathogen; preference; prenatal; prenatal exposure; prevent; public health priorities; public health relevance; randomized trial; safety study; septic; wound

DESCRIPTION (provided by investigator): The Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) study is a large pragmatic multi-center randomized clinical trial designed to evaluate the comparative effectiveness and safety of azithromycin-based extended-spectrum antibiotic prophylaxis (azithromycin plus standard narrow-spectrum cephalosporin) relative to standard single-agent cephalosporin prior to surgical incision to prevent post-cesarean infection. In contrast to cephalosporin, azithromycin is effective against other common pathogens, especially ureaplasma, a strong risk factor for post-cesarean endometritis when present in the chorioamnion, and the most common isolate from wound infections. Our preliminary studies suggest that extended-spectrum prophylaxis may effectively lower the risk of post-cesarean infection compared to standard cephalosporin alone. We will enroll women at high risk for post-cesarean infection despite standard prophylaxis - those undergoing a non-elective cesarean during labor or after membrane rupture. These women face a high likelihood of ascending colonization and infection with ureaplasmas from the lower genital tract. During the 4-year project period, 3 collaborating perinatal centers, recognized nationally for their expertise in the conduct of multi-center clinical trials, will randomize 2000 women undergoing non-elective (unscheduled) cesarean to either 500mg of intravenous azithromycin or identical placebo initiated prior to surgery; concurrently, both groups will also receive standard single-dose cefazolin prophylaxis (or clindamycin if allergic to cephalosporin). Women will be followed for at least 30 days according to CDC recommendations for ascertaining surgical site infections. Neonatal outcomes will also be recorded. The following specific aims will be addressed: Specific aim 1 (Effectiveness): To determine if pre-incision extended-spectrum prophylaxis reduces the risk of post-cesarean infection (endometritis, wound or other infections) compared to standard cephalosporin alone among women undergoing unscheduled cesarean delivery. {Specific aim 2 (Safety): To evaluate the safety of azithromycin-based pre-incision extended spectrum prophylaxis relative to standard cephalosporin prophylaxis in terms of the frequency of adverse composite and individual neonatal and maternal outcomes including suspected or proven neonatal infection, drug reactions or side effects including neonatal pyloric stenosis, and infection with resistant organisms.} {Specific aim 3: To collect and store biological specimens (umbilical cord blood and amniotic fluid) for future studies, primarily to assess the association between prenatal exposure to ureaplasmas and adverse neonatal outcomes (systemic inflammatory response syndrome, sepsis, pneumonia and bronchopulmonary dysplasia and death) and the potential for prenatal azithromycin use to prevent these outcomes.} PUBLIC HEALTH RELEVANCE: We propose a large multi-center randomized trial to evaluate the benefits and safety of an innovative antibiotic prophylaxis strategy at cesarean delivery to reduce the incidence of infection, one of the top 5 causes of pregnancy-related death and illness in the US. The regimen adds a second antibiotic to the standard cephalosporin to extend the spectrum of coverage to other common bacteria especially ureaplasmas. Preliminary data from a single center suggest that this extended-spectrum antibiotic prophylaxis regimen may significantly reduce post-cesarean infections among women undergoing cesarean delivery. The trial will be conducted at 3 Ob/Gyn departments experienced in the conduct of clinical trials: University of Alabama at Birmingham, University of North Carolina, Chapel Hill and University of Texas Medical Branch in Galveston.

描述（由研究者提供）：剖腹产最佳抗生素预防 (C/SOAP) 研究是一项大型务实多中心随机临床试验，旨在评估基于阿奇霉素的广谱抗生素预防（阿奇霉素加标准窄谱头孢菌素）相对于标准单药的有效性和安全性 手术切口前使用头孢菌素，以预防剖宫产后感染。与头孢菌素相比，阿奇霉素对其他常见病原体有效，尤其是解脲支原体，解脲支原体是存在于绒毛膜羊膜中时导致剖宫产后子宫内膜炎的强烈危险因素，也是伤口感染中最常见的分离株。我们的初步研究表明，与单独使用标准头孢菌素相比，广谱预防可以有效降低剖宫产后感染的风险。尽管采取了标准预防措施，我们仍将招募剖宫产后感染高风险的女性——那些在分娩期间或胎膜破裂后接受非选择性剖宫产的女性。这些女性很可能面临来自下生殖道的解脲脲原体的定植和感染。在为期 4 年的项目期间，3 个在进行多中心临床试验方面获得全国认可的合作围产期中心将随机将 2000 名接受非选择性（计划外）剖宫产的妇女随机分配到术前静脉注射 500 毫克阿奇霉素或相同的安慰剂；同时，两组患者还将接受标准单剂量头孢唑林预防治疗（如果对头孢菌素过敏则接受克林霉素）。根据 CDC 建议，将对女性进行至少 30 天的随访，以确定手术部位感染。新生儿结局也将被记录。将解决以下具体目标： 具体目标 1（有效性）：确定在接受计划外剖腹产的妇女中，与单独使用标准头孢菌素相比，切口前广谱预防是否可以降低剖腹产后感染（子宫内膜炎、伤口或其他感染）的风险。 {具体目标 2（安全性）：评估基于阿奇霉素的切开前广谱预防相对于标准头孢菌素预防的安全性，包括不良复合发生频率以及个别新生儿和孕产妇结局，包括疑似或证实的新生儿感染、药物反应或副作用（包括新生儿幽门狭窄和耐药微生物感染）。} {具体目标 3：收集和储存生物标本（脐带血和羊水）以供未来研究，主要是评估产前接触解脲支原体与不良新生儿结局（全身炎症反应综合征、脓毒症、肺炎和支气管肺发育不良和死亡）之间的关联，以及产前使用阿奇霉素预防这些不良结局的可能性 结果。} 公共健康相关性：我们提议进行一项大型多中心随机试验，以评估剖宫产时创新抗生素预防策略的益处和安全性，以降低感染发生率，感染是美国妊娠相关死亡和疾病的 5 大原因之一。该方案在标准头孢菌素的基础上添加了第二种抗生素，以扩大对其他常见细菌（尤其是解脲支原体）的覆盖范围。来自单一中心的初步数据表明，这种广谱抗生素预防方案可能会显着减少剖腹产妇女的剖腹产后感染。该试验将在 3 个具有临床试验经验的妇产科进行：阿拉巴马大学伯明翰分校、北卡罗来纳大学教堂山分校和德克萨斯大学加尔维斯顿医学分校。