Partial Oral Antibiotic Treatment for Bacterial Brain Abscess: an Open-label Randomised Non-inferiority Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 400
- 试验地点
- 4
- 主要终点
- Treatment failure
研究概览
简要总结
The investigators aim to determine if oral antibiotics are clinically acceptable as treatment of brain abscess. Following 2 weeks of standard intravenous antibiotic therapy, half of patients will continue with this treatment for another 4 weeks or longer while the other half will be assigned to oral antibiotics for the remaining duration of treatment.
详细描述
Treatment of brain abscess remains a considerable challenge due to the precarious location of the infection and the impenetrability of the blood-brain-barrier for most drugs. Thus, cure usually requires a combination of neurosurgical evacuation of abscess material and 6-8 weeks of high-dose intravenous (IV) antibiotic therapy to ensure eradication of bacteria within the abscess cavity. Disadvantages include risks of nosocomial infections and line-associated complications (e.g. bleeding, venous thrombosis, or need for replacement due to malfunction) in addition to the considerable costs of such long-term admission. However, improved insights into the pharmacokinetic properties and favourable bioavailability of some oral antibiotics may allow such treatment at an early stage. To date, there are no randomised controlled trials to guide treatment of bacterial brain abscess.
The investigators wish to determine whether a treatment strategy of transition to oral antibiotics after two weeks of treatment is non-inferior to continued IV antibiotics in clinically stable brain abscess patients assessed by the proportion with a favourable outcome at six months since randomisation.
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
- Single (Outcomes Assessor)
盲法说明
An independent blinded endpoint committee will assess the primary outcome.
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
- •A clinical presentation (e.g. headache, neurological deficit or fever) and cranial imaging (CT or MRI) consistent with brain abscess AND
- •The physician responsible for the patient decides to treat the patient for bacterial brain abscess AND
- •Ability to take and absorb oral medications (including by nasogastric tube) AND
- •To have received relevant antibiotic therapy for bacterial brain abscess for 14 consecutive days before randomisation AND
- •Expected to be treated with antibiotic therapy for at least another 14 days after time of randomisation AND
- •No progression in symptom intensity or occurrence of new-onset neurological symptoms (excluding seizures) within five days before time of randomisation.
- •Exclusion Criteria (patients fulfilling either criteria):
- •Expected substantially reduced compliance with treatment (e.g. IV drug abuse)
- •Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women <50 years of age)
- •Concomitant (empirical) brain abscess treatment for tuberculosis, nocardiosis, Pseudomonas spp., fungi, toxoplasmosis or other CNS parasites
- •Device related brain abscesses (e.g. deep brain stimulators, ventriculo-peritoneal shunts)
- •Severe immuno-compromise defined as ongoing need for biological- or chemotherapy, prednisolone >20 mg/day for 14 days or longer, uncontrolled HIV/AIDS, haematological malignancies, and organ transplant recipients
- •Concomitant or unrelated infections necessitating IV antibiotics beyond seven days of duration after time of randomisation
- •Previous enrolment into this trial
排除标准
- 未提供
研究组 & 干预措施
Oral antibiotics
Patients will be randomised to oral antibiotics after two weeks of appropriate antibiotic therapy for bacterial brain abscess since definitive aspiration/excision of brain abscess or, in case of no planned diagnostic neurosurgical procedure, since initiation of guideline recommended antibiotics for bacterial brain abscess
干预措施: Early transition to oral antibiotics (Drug)
Standard treatment
Patients will be randomised to continuation of standard intravenous antibiotics after two weeks of appropriate antibiotic therapy for bacterial brain abscess since definitive aspiration/excision of brain abscess or, in case of no planned diagnostic neurosurgical procedure, since initiation of guideline recommended antibiotics for bacterial brain abscess
干预措施: Standard treatment of intravenous antibiotics (Drug)
结局指标
主要结局
Treatment failure
时间窗: Six months after randomisation
A composite of number of participants with all-cause mortality, risk of intraventricular rupture of brain abscess (IVROBA), unplanned neurosurgery, relapse, or recurrence
次要结局
- Unfavourable outcome(At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation)
- Unplanned neurosurgery(At 6 months since randomisation)
- IVROBA(At 6 months since randomisation)
- Recurrence(At 6 months since randomisation)
- Central line associated complications(6 months since randomisation)
- SAE(From randomisation until last day of antibiotic treatment for brain abscess)
- Cognitive impairment(At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation)
- Treatment failure(At last day of antibiotic treatment for brain abscess, and 3- and 12-months after randomisation)
- All-cause mortality(At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation)
- Relapse(At 6 months since randomisation)
- Clostridial diarrhea(From randomisation up until last day antibiotic treatment for brain abscess)
- SF36(At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation)
- Duration of treatment(From randomisation until last day of antibiotic treatment for brain abscess up to 6 months since randomisation)
- Oedema on cranial imaging(3 months since randomisation)
- EQ-5D-5L(At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation)
- EQ-VAS(At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation)
- Unfavourable outcome - sliding dichotomy(At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation)
- Adherence to treatment(From randomisation until last day of antibiotic treatment for brain abscess, assessed up to 6 months since randomisation)
- Duration of admission(From randomisation until hospital discharge to home or rehabilitation unit or death, whichever comes first, assessed up to 6 months)
研究者
Henrik Nielsen
Professor
Aalborg University Hospital