Division of Infectious Diseases & Clinical Epidemiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
BMJ Open. 2020 May 11;10(5):e038300. doi: 10.1136/bmjopen-2020-038300.
Bloodstream infections are a leading cause of mortality and morbidity; the duration of treatment for these infections is understudied.
We will conduct an international, multicentre randomised clinical trial of shorter (7 days) versus longer (14 days) antibiotic treatment among hospitalised patients with bloodstream infections. The trial will include 3626 patients across 60 hospitals and 6 countries. We will include patients with blood cultures confirming a pathogenic bacterium after hospital admission. Exclusion criteria will include patient factors (severe immunosuppression), infection site factors (endocarditis, osteomyelitis, undrained abscesses, infected prosthetic material) and pathogen factors (, , and contaminant organisms). We will leave the selection of specific antibiotics, doses and route of delivery to the discretion of treating physicians; no placebo control will be used given the diversity of pathogens and sources of bacteraemia. The intervention will be assignment of treatment duration to be 7 versus 14 days. We will minimise selection bias via central randomisation with variable block sizes, with concealed allocation until day 7 of adequate antibiotic treatment. The primary outcome is 90-day survival; we will test whether 7 days is non-inferior to 14 days of treatment, with a non-inferiority margin of 4% absolute mortality. Secondary outcomes include hospital and intensive care unit (ICU) mortality, relapse rates of bacteraemia, hospital and ICU length of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, infection, antibiotic allergy and adverse events and colonisation/infection with antibiotic-resistant organisms.
The study has been approved by the ethics review board at each participating site. Sunnybrook Health Sciences Centre is the central ethics committee. We will disseminate study results via the Canadian Critical Care Trials Group and other collaborating networks to set the global paradigm for antibiotic treatment duration for non-staphylococcal Gram-positive, Gram-negative and anaerobic bacteraemia, among patients admitted to hospital.
The BALANCE (Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness) trial was registered at www.clinicaltrials.gov (registration number: NCT03005145).
血流感染是导致死亡率和发病率的主要原因；这些感染的治疗持续时间研究不足。
我们将在国际范围内，对住院血流感染患者进行更短（7 天）与更长（14 天）抗生素治疗的多中心随机临床试验。该试验将包括 6 个国家的 60 家医院的 3626 名患者。我们将纳入在住院后血培养证实病原菌的患者。排除标准包括患者因素（严重免疫抑制）、感染部位因素（心内膜炎、骨髓炎、未引流脓肿、感染性假体）和病原体因素（、、和污染菌）。我们将把具体抗生素的选择、剂量和给药途径留给治疗医生决定；由于病原体和菌血症来源的多样性，不使用安慰剂对照。干预措施将是将治疗持续时间设定为 7 天与 14 天。我们将通过中央随机化和可变大小的块来尽量减少选择偏倚，直到充分抗生素治疗的第 7 天为止，分配是隐藏的。主要结局是 90 天生存率；我们将测试 7 天是否不劣于 14 天的治疗，非劣效性边界为 4%的绝对死亡率。次要结局包括医院和重症监护病房（ICU）死亡率、菌血症复发率、医院和 ICU 住院时间、机械通气和血管加压素持续时间、无抗生素天数、感染、抗生素过敏和不良事件以及抗生素耐药菌的定植/感染。
该研究已获得每个参与地点的伦理审查委员会的批准。桑尼布鲁克健康科学中心是中央伦理委员会。我们将通过加拿大危重病临床试验组和其他合作网络传播研究结果，为非葡萄球菌革兰阳性、革兰阴性和厌氧菌血症住院患者的抗生素治疗持续时间制定全球范例。
BALANCE（血流感染抗生素治疗实际需要以达到临床效果）试验在 www.clinicaltrials.gov 上登记（注册号：NCT03005145）。
