Partial Oral Antibiotic Treatment for Bacterial Brain Abscess

Phase 4RecruitingNCT04140903

Henrik Nielsen400 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

400

Conditions

Brain Abscess Cerebral Abscess

Interventions

Early transition to oral antibioticsDRUG

Patients will be treated with an oral antibiotic regimen (e.g. amoxicillin + metronidazole) based upon pharmacokinetic and pharmacodynamic properties of the drugs, pathogen susceptibility, and any existing drug allergies or interactions

Standard treatment of intravenous antibioticsDRUG

Patients will continue standard intravenous antibiotic therapy for brain abscess (e.g. 3rd generation cephalosporin + metronidazole) according to international guidelines and pathogen susceptibility patterns.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. A clinical presentation (e.g. headache, neurological deficit or fever) and cranial imaging (CT or MRI) consistent with brain abscess AND 2. The physician responsible for the patient decides to treat the patient for bacterial brain abscess AND 3. Ability to take and absorb oral medications (including by nasogastric tube) AND 4. To have received relevant antibiotic therapy for bacterial brain abscess for 14 consecutive days before randomisation AND 5. Expected to be treated with antibiotic therapy for at least another 14 days after time of randomisation AND 6. 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): 1. Expected substantially reduced compliance with treatment (e.g. IV drug abuse) 2. Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women \<50 years of age) 3. Concomitant (empirical) brain abscess treatment for tuberculosis, nocardiosis, Pseudomonas spp., fungi, toxoplasmosis or other CNS parasites 4. Device related brain abscesses (e.g. deep brain stimulators, ventriculo-peritoneal shunts) 5. 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 6. Concomitant or unrelated infections necessitating IV antibiotics beyond seven days of duration after time of randomisation 7. Previous enrolment into this trial

Locations (4)

Aalborg University Hospital

Aalborg, Denmark

RECRUITING

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

Outcomes

Primary Outcomes

Treatment failure

A composite of number of participants with all-cause mortality, risk of intraventricular rupture of brain abscess (IVROBA), unplanned neurosurgery, relapse, or recurrence

Time frame: Six months after randomisation

Secondary Outcomes

Treatment failure

A composite of number of participants with all-cause mortality, risk of intraventricular rupture of brain abscess (IVROBA), unplanned neurosurgery, relapse, or recurrence

Time frame: At last day of antibiotic treatment for brain abscess, and 3- and 12-months after randomisation

Unfavourable outcome

Number of participants with Extended Glasgow Outcome Scale score \<7, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

Time frame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation

All-cause mortality

Number of participants with fatal outcome, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

Time frame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation

Unplanned neurosurgery

Number of participants with unplanned (re-)aspiration or excision, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

Time frame: At 6 months since randomisation

IVROBA

Number of participants with intraventricular rupture of brain abscess, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

Central Contacts

Jacob Bodilsen, MD

CONTACT

+45 97663920 jacob.bodilsen@rn.dk

Henrik Nielsen, Professor

CONTACT

+45 97663920 henrik.nielsen@rn.dk

Data from ClinicalTrials.gov

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