Partial Oral Antibiotic Treatment for Bacterial Brain Abscess

NCT ID: NCT04140903

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-06
• Study Completion Date: 2028-08-31

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.

Conditions

Brain Abscess; Cerebral Abscess

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: EXPERIMENTAL

Early transition to oral antibiotics

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Standard treatment of intravenous antibiotics

Intervention Type: DRUG

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

Interventions

Early transition to oral antibiotics

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

Intervention Type: DRUG

Standard treatment of intravenous antibiotics

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

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Henrik Nielsen

OTHER

Sponsor Role: lead

Responsible Party

Henrik Nielsen

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jacob Bodilsen, MD

Role: PRINCIPAL_INVESTIGATOR

Aalborg University Hospital

Locations

Aalborg University Hospital

Aalborg, , Denmark

Site Status: RECRUITING

Aarhus University Hospital

Aarhus, , Denmark

Site Status: RECRUITING

Rigshospitalet

Copenhagen, , Denmark

Site Status: RECRUITING

Odense University Hospital

Odense, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Jacob Bodilsen, MD

Role: CONTACT

jacob.bodilsen@rn.dk

+45 97663920

Henrik Nielsen, Professor

Role: CONTACT

henrik.nielsen@rn.dk

+45 97663920

Facility Contacts

Jacob Bodilsen, MD PhD

Role: primary

Merete Storgaard, MD

Role: primary

Lars H Omland, MD

Role: primary

Lykke Larsen, MD

Role: primary

References

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.

Reference Type: DERIVED

PMID: 34772441 (View on PubMed)

Other Identifiers

1

Identifier Type: -

Identifier Source: org_study_id