Reduction of Antibiotherapy Duration for Infections on Implantable Extra Cardiac Devices Leads: a Randomized Controlled Multicenter Non-inferiority Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 500
- 主要终点
- Mortality,
研究概览
简要总结
The design is an Open-label randomized controlled multicenter non-inferiority trial with blinded assessor which compares 2 antibiotic strategy: 14-day antibiotic therapy after removal of infected material (experimental group) versus 28-day antibiotic therapy after removal of infected material (control group).
Randomization will be centralized, individual 1:1, stratified on center and age (<75 versus >=75 years). Analysis will be reported following CONSORT guidelines for pharmacological trials.
Main analysis will be conducted according to per protocol and intent-to-treat principles. Subgroup analysis will be conducted according to age, classes of antibiotics at baseline and according to resistance testing and baseline renal clearance.
详细描述
Infections of cardiac implantable electronic devices (CIED) are one of the most frequent complication after implantation of these devices, with an incidence rate estimated at 4.82 / 1000 in Denmark, mainly in the first year post implantation. An american study found that the incidence of CIED infection in the USA increased from 1.53% in 2004 to 2.41% in 2008 and a National Inpatient Sample database study showed an increase from 1.45% to 3.41% (P<0.001) from 2000 through 2012. These figures are constantly increasing and concern mostly older people.
Although the mortality seems to be low compared to those of valvular infection , evaluated at 4% for nonstaphylococcal infection and up to 9% for Staphylococcus aureus related infections, those infections are responsible of numerous morbidities such as iterative hospitalizations, decompensations of other comorbidities and autonomy loss, especially, for older people
Clinical presentations of CIED infections are varied and include generator pocket infections, native or prosthetic CIED-associated valvular endocarditis (CIED-IE) with echocardiographic evidence of valve involvement, and CIED lead infections (CIED-LI) with evidence of lead infection without valve involvement.
In CIED infections, removal of the device is the cornerstone of treatment and is usually required to enable cure in association with antimicrobial therapy for a few weeks. However, although antimicrobial therapy duration after removal of the device are relatively well defined for generator pocket infections (10 - 14 days for the remaining skin and soft tissue infection) and CIED-IE (4 - 6 weeks), the optimal duration of antibiotic treatment in CIED-LI has yet to be determined.
Several series amalgamate generator pocket infection, CIED-IE and CIED-LI descript duration of therapy and are therefore unhelpful in deciding on the optimum duration of antimicrobials.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Diagnosis of CIED leads infections, defined by:
- •Symptoms/signs of systemic infection AND positive blood cultures fulfilled the major Duke microbiological criteria AND echocardiography consistent with vegetation(s) attached to lead(s) AND/OR [18F]FDG PET/CT or radiolabelled WBC SPECT/CT detection of abnormal activity along leads OR
- •Symptoms/signs of systemic infection AND NO, signs of generator pocket infection, AND culture, histology or molecular evidence of infection on explanted lead.
- •Complete removal of the infected CIED
- •Signed informed consent
- •French National Health Assurance
排除标准
- •Current involvement of native or prosthetic heart valve
- •Distant infectious foci (such as haematogenous vertebral osteomyelitis, pulmonary abscess...) justifying a prolonged duration of therapy.
- •Positive blood culture > 24 hours after cultures despite CIED removal
- •CIED infection with Mycobacteria or Fungi
- •Women who are pregnant or nursing
- •Females of childbearing potential without effective method of birth control
- •Patients who are under tutorship or curatorship
研究组 & 干预措施
Experimental group
14-day antibiotic therapy after removal of infected material
干预措施: 14-day antibiotic therapy (Drug)
control group
28-day antibiotic therapy after removal of infected material
干预措施: 28-day antibiotic therapy (Drug)
结局指标
主要结局
Mortality,
时间窗: at 3 months after randomization,
Mortality linked to infection during or after antibiotic therapy
Rate of relapse of infection
时间窗: at 6 months after randomization
Number of patient whith relapse of infection defined by diagnostic of endocarditis or CIED infection with the same bacteria
Rate of a distant infections
时间窗: at 3 months after randomization
Rate of a distant infectious foci with the same bacteria
Rate of a distant infectious
时间窗: 6 months after randomization
Rate of diagnostic of a distant infectious foci with the same bacteria
次要结局
- Percentage of emergency consultation,(within 6 months after the end of antibiotherapy)
- Rate of Acute Renal failure,(at 6 months after the end of the antibiotherapy)
- Percentage of unplanned hospitalization(within 6 months after the end of antibiotherapy)
- percentage of adverse events related to antibiotherapy(within 6 months after the end of antibiotherapy)
- Rate of allergy grade III or IV(at 6 months after the end of antibiotherapy)
- Rate of Clostridium difficile colitis,(at 6 months after the end of antibiotherapy)