Clinical trial NCT04140903: Partial Oral Antibiotic Treatment for Bacterial Brain Abscess
Official title: Partial Oral Antibiotic Treatment for Bacterial Brain Abscess: an Open-label Randomised Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Brain Abscess
Cerebral Abscess
Keywords: Oral antibiotics
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2019-10-28
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator-initiated, international, multi-centre, randomised, parallel groups, non-inferiority trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment failure
timeFrame: Six months after randomisation
Secondary outcomes:
measure: Treatment failure
timeFrame: At last day of antibiotic treatment for brain abscess, and 3- and 12-months after randomisation
measure: Unfavourable outcome
timeFrame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
measure: All-cause mortality
timeFrame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
measure: Unplanned neurosurgery
timeFrame: At 6 months since randomisation
measure: IVROBA
timeFrame: At 6 months since randomisation
measure: Relapse
timeFrame: At 6 months since randomisation
measure: Recurrence
timeFrame: At 6 months since randomisation
measure: Unfavourable outcome - sliding dichotomy
timeFrame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
measure: Central line associated complications
timeFrame: 6 months since randomisation
measure: Clostridial diarrhea
timeFrame: From randomisation up until last day antibiotic treatment for brain abscess
measure: Duration of admission
timeFrame: From randomisation until hospital discharge to home or rehabilitation unit or death, whichever comes first, assessed up to 6 months
measure: Duration of treatment
timeFrame: From randomisation until last day of antibiotic treatment for brain abscess up to 6 months since randomisation
measure: Adherence to treatment
timeFrame: From randomisation until last day of antibiotic treatment for brain abscess, assessed up to 6 months since randomisation
measure: Oedema on cranial imaging
timeFrame: 3 months since randomisation
measure: SAE
timeFrame: From randomisation until last day of antibiotic treatment for brain abscess
measure: SF36
timeFrame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
measure: EQ-5D-5L
timeFrame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
measure: EQ-VAS
timeFrame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
measure: Cognitive impairment
timeFrame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Aalborg University Hospital
name: Jacob Bodilsen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bodilsen J, Brouwer MC, van de Beek D, Tattevin P, Tong S, Naucler P, Nielsen H. Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL). Trials. 2021 Nov 12;22(1):796. doi: 10.1186/s13063-021-05783-8.