SIS multicenter study of duration of antibiotics for intraabdominal infection

描述（由申请人提供）：腹内感染的最佳抗生素治疗持续时间尚不清楚，已被外科感染学会确定为临床研究的重中之重。我们研究的最终目的是优化（并减少）全世界腹腔内感染抗生素治疗的持续时间。待验证的假设是，与在充分的手术或经皮介入治疗中基于生理参数解决的疗程相比，四天的腹腔内感染治疗将导致相似的结果和更短的治疗时间。这个建议是一个多中心，随机，双盲（直到治疗的第四天），一项非劣效性临床试验，比较预定4天的抗生素治疗与在白细胞计数（= 11000 /ul）和全身温度（< 38.0℃）整整一天（最多10天的抗生素治疗）正常化后一天终止的抗生素治疗，并对其进行充分的源控制。纳入标准包括年龄= 16岁，能够获得患者或代理人的知情同意，是否存在需要任何住院时间的腹腔内感染，并采用开放、腹腔镜或经皮介入治疗，以及当地研究者和主要研究者认为有足够的源头控制。将纳入1120名患者，以确保有足够的权力来评估两组的等效性。主要终点将是由指定的抗生素治疗持续时间（治疗意向分析）决定的失败率。失败定义为需要再次干预（手术或经皮），手术部位感染，或在最初的腹腔感染干预后30天内死亡。此外，将评估多个次要终点，包括抗生素治疗的持续时间和非腹部和非手术伤口部位的感染发生率，特别是抗生素耐药病原体。我们研究的最终目标是改变全世界的做法，特别是通过缩短抗生素治疗腹腔内感染的持续时间，从而减少资源利用和减少抗生素耐药病原体的选择。

DESCRIPTION (provided by applicant): The optimum duration of antibiotic therapy for intraabdominal infection remains unknown and has been identified by the Surgical Infection Society as a high priority for clinical research. The ultimate objective of our research is to optimize (and reduce) the duration of antibiotic therapy for intraabdominal infection throughout the world. The hypothesis to be tested is that four days of therapy for intraabdominal infection will lead to similar outcomes and a shorter duration of therapy when compared to a course based on the resolution of physiologic parameters in the setting of adequate operative or percutaneous intervention. This proposal is for a multicenter, randomized, double-blind (until the fourth day of therapy), non-inferiority clinical trial comparing a predetermined four days of antibiotic therapy to antibiotic therapy terminated one day after normalization of white blood cell count (= 11,000/ul) and normalization of systemic temperature (< 38.0¿ C) for one whole calendar day (and a maximum of 10 days of antibiotic therapy) in the setting of complicated intraabdominal infection treated with adequate source control. Inclusion criteria include age = 16 years, ability to obtain informed consent from the patient or surrogate, presence of an intraabdominal infection requiring any duration of hospitalization and managed with open, laparoscopic, or percutaneous intervention, and, adequate source control in the opinion of the local investigator and Principal Investigator. 1,120 patients will be enrolled to ensure adequate power to assess equivalence of the two arms. The primary endpoint will be percentage failure conditioned by assigned duration of antibiotic therapy (intent to treat analysis). Failure will be defined as need for reintervention (surgical or percutaneous), surgical site infection, or death within 30 days of the original intervention for intraabdominal infection. In addition, multiple secondary endpoints will be assessed, including duration of antibiotic therapy and the incidence of infection at non-abdominal and non-surgical wound sites, particularly with antibiotic-resistant pathogens. The ultimate objective of our research is to change practice throughout the world, specifically by shortening the duration of antibiotic therapy for intraabdominal infections and thus decreasing resource utilization and decreasing the selection of antibiotic-resistant pathogens.