SIS multicenter study of duration of antibiotics for intraabdominal infection

描述（由申请人提供）：抗生素治疗腹腔内感染的最佳持续时间仍然未知，已被外科感染学会确定为临床研究的高度优先事项。我们研究的最终目标是优化（和减少）全世界腹腔感染抗生素治疗的持续时间。待检验的假设是，与基于在适当手术或经皮干预的情况下生理参数的解决方案的疗程相比，腹腔内感染的4天治疗将导致相似的结局和更短的治疗持续时间。本提案是一项多中心、随机、双盲（直至治疗第4天），比较预定4天抗生素治疗与白色血细胞计数正常化后1天终止抗生素治疗的非劣效性临床试验（= 11，000/ul）和全身温度正常化（< 38.0分）C.一整天（和最多10天的抗生素治疗）在复杂的腹腔内感染的情况下，充分的源头控制治疗。入选标准包括年龄≥ 16岁，能够获得患者或代理人的知情同意书，存在需要住院治疗的腹腔内感染，并通过开放性、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适当的源控制。将招募1，120名患者，以确保有足够的把握度来评估两组的等效性。主要终点将是以指定的抗生素治疗持续时间为条件的失败百分比（意向治疗分析）。失败定义为需要再次介入（手术或经皮）、手术部位感染或腹腔内感染初始介入后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以及非腹部和非手术伤口部位的感染发生率，特别是耐药性病原体。我们研究的最终目标是改变世界各地的实践，特别是通过缩短腹腔内感染抗生素治疗的持续时间，从而降低资源利用率，减少耐药病原体的选择。

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.